["Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: Recent studies have shown that the immune system plays a crucial role in the clearance of HAdV viremia and survival of the host . Chen et al. reported that, in the acute phase of HAdV-55 infection, patients with severe disease may have high levels of dendritic cells and Th17 cells . In our study, the only patient who recovered from severe infection had higher T-cell counts. Three of the five patients had relatively low T-cell counts when admitted. Our results suggest that these three patients may have been relatively immunocompromised and that a lower T-cell count may be a risk Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Recent studies have shown that the immune system plays a crucial role in the clearance of HAdV viremia and survival of the host . Chen et al. reported that, in the acute phase of HAdV-55 infection, patients with severe disease may have high levels of dendritic cells and Th17 cells . In our study, the only patient who recovered from severe infection had higher T-cell counts. Three of the five patients had relatively low T-cell counts when admitted. Our results suggest that these three patients may have been relatively immunocompromised and that a lower T-cell count may be a risk Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: Laboratory findings for the HAdV-7-positive inpatients were also significantly different from those infected by HAdV-3 . Specifically, the HAdV-7-positive inpatients had lower white blood cell count , platelet count . In contrast, hemoglobin and C-reactive protein levels, and the percentages of lymphocytes, neutrophils and positive sputum culture were found to be statistically similar. Title: Human adenovirus type 7 infection causes a more severe disease than type 3\nPassage: Imaging and laboratory data on admission and during hospitalization were collected. White blood cell count > 15,000/ \u03bcL was defined as leukocytosis, whereas that < 4000/\u03bcL was defined as leukopenia.", "Title: Gene Knockdowns in Adult Animals: PPMOs and Vivo-Morpholinos\nPassage: Global Therapeutics, the cardiology unit of Cook Medical , is developing PPMO-coated stents for balloon angioplasty using PPMOs from AVI BioPharma Inc. The Morpholino moiety targets c-myc to inhibit proliferation of the vascular endothelial cells, which might otherwise cause restenosis. Title: Gene Knockdowns in Adult Animals: PPMOs and Vivo-Morpholinos", "Passage: Typically the highest antiviral efficacies are achieved with pre-infection administration of the PPMO followed by a series of post-infection doses. Recent studies explicitly comparing effects of unmodified Morpholino oligos and PPMOs show that the PPMOs are far more effective in vivo. Viral applications of PPMOs have recently been reviewed so only a few recent papers applying PPMOs to inhibit viruses will be considered here. Title: Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles", "Passage: To assess the replication efficiency of the different vectors, multi-step growth kinetics of cell-associated and released virus were performed following infection at low MOI = 0.03 . Compared to the GFP-encoding control virus MV vac2 -GFP, MVs encompassing the DisOva transgene cassette together with or without MLV gag grew with similar kinetics and reached similar maximum titers as the control virus. Thus, cloning and rescue of both MVs-derived vectors resulted in expression of the inserted antigen in infected cells without impact on viral replication or genetic stability. Antigen-specific cellular immunity against vector and transgene is induced by Ova-presenting MV. To Title: Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles", "Passage: Generation and characterization of recombinant MV vac2 encoding different forms of the Ovaantigen. To was chosen since especially the cellular immune-responses and respective immune-dominant peptides in mice such as used in our studies are well known and can thus considerably support characterization of such responses. For this purpose, Ova was genetically fused to the transmembrane domain of the platelet-derived growth factor receptor giving rise to a membrane-bound extracellular variant that should be readily incorporated into retroviral particles . A recombinant MV encoding DisOva in an additional transcription unit following the P gene in combination with a second, MLV Gag-encoding transgene", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: for human sero-surveys. These relied on MERS-CoV-infected cell culture as an antigen source, detecting the presence of human anti-MERS-CoV IgG, IgM or neutralizing antibodies in human samples . No sign of MERS-CoV antibodies was found among 2,400 sera from patients visiting Hospital in Jeddah, from 2010 through 2012, prior to the description of MERS-CoV . Nor did IFA methods detect any sign of prior MERS-CoV infection among a small sample of 130 healthy blood donors from another Hospital in Jeddah . Of 226 slaughterhouse workers, only eight were positive by IFA, and those sera could not be confirmed by virus Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Strategic, widespread sero-surveys of humans using samples collected after 2012 are infrequent. Much of the Arabian Peninsula and all of the Horn of Africa lack baseline data describing the proportion of the community who may have been infected by a MERS-CoV. However, sero-surveys have had widespread use in elucidating the role of DCs as a transmission source for MERS-CoV. Because of the identity shared between DC and human MERS-CoV , serological assays for DC sero-surveys should be transferrable to human screening with minimal re-configuration. Also, no diagnostically relevant variation in neutralization activity have been found from among a range of Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: human sera, a tiered diagnostic process assigned both recombinant IFA and recombinant ELISA positive sera to 'stage 1' seropositivity. A stage 2 seropositive result additionally required a suitably titred PRNT result . The study found 15 sera collected in 2012 to 2013 from 10,009 people in 13 KSA provinces contained MERS-CoV antibodies, but significantly higher proportions in occurred in camel shepherds and slaughterhouse workers . Contemporary surveys are needed. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The first sero-survey of livestock living in the Middle East region was conducted during 2012-2013 . DCs were sampled from a mostly Canary Island-born herd and from Omani DCs . A neutralising antibody assay found only 10 % of strongly seropositive Canary Island . b Camel-to-human infections appear to be infrequent, while human-to-human spread of infection is regularly facilitated by poor IPC in healthcare settings where transmission is amplified, accounting for the bulk of cases. There are human MERS cases that do not fall into either category of source and it is unclear if these acquired infection through some entirely", "Title: Kinome-Wide siRNA Screening Identifies Src-Enhanced Resistance of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells\nPassage: MDA-MB-231 and Hs578T cells were seeded at density of 2 \u00d7 10 4 in NanoCulture plates in the presence of 10 nM siRNA. The cells were cultured for 3 days until tumorsphere formation. The tumorsphere were then treated with anticancer drugs for 48 h and stained with Calcein AM and Ethidium homodimer-1 for live and dead cell population, respectively. The cells treated with or without 70% methanol for 30 min were considered as a relative control for all dead or live cells. The live and dead cells were then observed under microscopy and quantitated with Fluoroskan Ascent FL reader as Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: The generation of MDMs has been described in previous studies . Briefly, PBMCs were isolated from human whole blood by density-gradient centrifugation over Histopaque . Monocytes were purified using human CD14-specific microbeads following manufacturer's instructions. CD14 + monocytes were differentiated into MDMs by culturing for 6-7 days with recombinant human macrophage colony-stimulating factor and conditioned medium from KPB-M15 cells . Media were replaced every 2-3 days during the incubation for a total of 6-7 days. The cells were harvested and plated on desired 96-well plates 1 day prior to the drug screen assay. The differentiated MDMs were characterized by flow Title: Novel prostate cancer immunotherapy with a DNA-encoded anti-prostate-specific membrane antigen monoclonal antibody", "Passage: To detect cell surface PSMA, tubes of 1.0 \u00d7 10 6 LNCaP or TRAMP-C2 cells were washed with phosphate-buffered saline , stained with live/dead fixable violet dead cell stain for 15 min, and then washed twice with FACS buffer . Cells were next incubated for 30 min at room temperature with a 1:4 dilution of day 14 sera from PSMA-DMAb plasmid-injected mice and then washed. Finally, cells were incubated in the dark for 30 min with a 1:100 dilution of PE-conjugated anti-human Fc IgG , followed by a final wash with FACS buffer. Samples were resuspended in 1\u00d7 stabilizing fixative Title: Evaluation of Ultra-Microscopic Changes and Proliferation of Apoptotic Glioblastoma Multiforme Cells Induced by Velogenic Strain of Newcastle Disease Virus AF2240", "Passage: Acridine Orange Double staining DBTRG .05MG cells were stained using propidium iodide and acridine-orange double staining according to standard procedures and examine under a fluorescence microscope N . DBTRG .05MG cells were seeded in 6-well plate and incubated at 37 o C in 5%CO 2 atmosphere. Twenty-four hours later, the medium in each well was removed and replaced with NDV at IC 50 concentration dissolved in the culture medium and incubated at 37 o C in 5%CO 2 atmosphere for 72 hours. After the incubation period, detached cells in the medium were collected and added back to trypsinised adherent cells.", "Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009\nPassage: the population of Reunion Island and a Chi2 test was used to analyse differences in age, sex and geographic location. Cumulative incidence rates of infection and seroconversion rates were standardized according to the age structure of the community source). Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: Based on clinical cases reported to the epidemiological surveillance services , it was estimated that 66,915 persons in Reunion Island who consulted a physician were infected by the pH1N1/2009 virus during the 9 weeks of the epidemic, giving a cumulative attack rate of 8.26%. Taking into account those who did not consult a physician, the number of symptomatic infected persons was estimated to 104,067 . In fact, the attack rate of pH1N1/2009 infection in our serosurvey was about 42%-44% at the peak of the antibody response , a figure which is at least 3 to 4 times higher than rates Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: Reunion Island is a French overseas department located in the southwestern Indian Ocean, 700 km east of Madagascar and 200 km southwest of Mauritius. The first imported case of pH1N1/2009v was identified on 5 th July 2009 in a traveller returning from Australia. The first case indicating community transmission was detected on 21 st July . pH1N1/2009v became the predominant circulating influenza virus within four weeks of its first detection, its activity peaked during week 35 and ended at week 38 . Contrary to initial fears, the health care system was not overwhelmed, as morbidity and mortality rates were lower Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: R\u00e9union Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean . The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance , based on the surveillance system of mainland France . Influenza activity generally increases during austral winter, corresponding to summer in Europe . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern", "Title: Complete viral RNA genome sequencing of ultra-low copy samples by sequence-independent amplification\nPassage: All consensus genome assemblies generated as part of this project were submitted to NCBI's GenBank database . Illumina read data was submitted to NCBI's Short Read Archive under Trace Identifiers SRR513075, SRR513078, SRR513080, SRR513086-87, SRR513092, and SRR527699-726. Title: Generation and comparative genomics of synthetic dengue viruses", "Passage: Three DENV cDNA samples were sequenced and analyzed: one of the samples was the wildtype strain, with the WT sequence used as a reference genome for NGS analysis. The two synthetic variants of the virus were synthesized using two different methods . The WT sequence can be found in Additional file 1, section 8. Sequencing libraries were prepared using the INCPM DNA-seq protocol, and sequenced 2 \u00d7 150 on an Illumina MiSeq nano v2 PE150. Sequenced reads were mapped to a reference genome using BWA MEM v0.75 . Among all read-pairs with the same alignment, a single representative read was Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study", "Passage: Purified PCR products were sequenced directly. Primer sequences are available upon request. The sequencing reaction was performed by ABI PRISM \u00ae BigDye\u2122 Terminators v3.1 Cycle Sequencing Kit as described previously . The sequences were developed on an automatic ABI PRISM \u00ae 3130 genetic analyzer with 80 cm capillaries. Consensus sequences were generated in SeqScape \u00ae Software v2.5 . Sequence assembly, multiple alignment and alignment trimming were performed with the BioEdit software v.7.0.5 . Distance based neighbor joining phylogenetic trees and character based maximum parsimony trees were generated using the Molecular Evolutionary Genetics Analysis software v.3.1 . Maximum likelihood trees were Title: Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers", "Passage: Ultimately, the data set consisted of 686 DNA and RNA libraries, for which 2\u02c6100 bp paired end sequencing was performed using the Illumina HiSeq 2000 platform at BGI-Europe, Copenhagen, Denmark. The 686 sequencing libraries thus originated from 252 different cancer samples, 32 non-template controls, and 24 exogenous controls. The distribution of methods, libraries and controls for each sample type is provided in Table S2 . Samples were preferably analysed with multiple methods, thus 165 out of 252 samples were analysed with more than one laboratory method .", "Title: Asymmetry in the Presence of Migration Stabilizes Multistrain Disease Outbreaks\nPassage: Finally, the work discussed here shows a potential effect of human movement between heterogeneous regions. As spatial effects are further studied in epidemic models, it remains to be seen how this phenomenon will extend to more complicated spatial geometries, including more patches and perhaps non-symmetric coupling terms. This work represents a first step towards understanding the role of migration and spatial heterogeneity in dynamical properties of dengue observed in epidemiological data, such as traveling waves of infection in Thailand . Furthermore, because the migration-induced stabilization depends only on the existence of a Hopf bifurcation in the model, it is expected Title: Asymmetry in the Presence of Migration Stabilizes Multistrain Disease Outbreaks", "Passage: Bifurcations from steady state to oscillatory behavior can be associated with an increased number of infection cases, particularly if chaotic oscillations occur, as in previous dengue models . Our results suggest that if control strategies in one region are able to generate enough asymmetry, this could lead to a stabilization of the outbreaks, which would have a positive effect on adjacent regions. Asymmetry could be generated in the effective contact rate by mosquito control, which could include reducing mosquito breeding sites , or through new genetic controls which are under development . Asymmetry in the birth rate could be generated Title: Asymmetry in the Presence of Migration Stabilizes Multistrain Disease Outbreaks", "Passage: To motivate this result, we diffusively coupled two low dimensional Hopf bifurcations with different characteristic frequencies and analyzed the stability of the steady state. We again saw that coupling between asymmetric systems led to stabilization. This indicates that the stabilization in the epidemic model is a result of the underlying dynamics, rather than the details of the model. We suggest that the stabilization may occur as a result of the two different coupled frequencies generating oscillations that tend to cancel each other because of phase differences. This topic will be studied in more detail in a future work. Title: Globalization and emerging governance modalities", "Passage: cannot afford grain. Structural inequalities coupled with civil unrest already produce widespread hunger, malnourishment and famine. An environmental disaster in a large population, most obviously China or India, could have devastating effects within the world system. This, of course, is the great fear environmentalists have for dependence on mono-cropping, species loss, and water management 5 .", "Title: Neutralization Interfering Antibodies: A \u201cNovel\u201d Example of Humoral Immune Dysfunction Facilitating Viral Escape?\nPassage: The S protein of CoVs is inserted in the envelope of the virion mediating binding and fusion events necessary for infection, and it is the major target of the humoral protective immunity . Although the S protein of SARS-CoV shares little aminoacid identity , it shares common structural features with S proteins of the other members of the Coronaviridae family. SARS-S protein is a type I transmembrane glycoprotein of approximately 1,255 amino acids in length and divided into two functional domains: S1 and S2 . In many CoVs, the S protein is cleaved during biogenesis and these two functional domains Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Previous studies demonstrated that the N-terminal 40 amino acids of the SARS-CoV E protein are important for ion channel formation, and that mutations N15A and V25F ] prevent ion conductivity . In addition, the SARS-CoV 3a protein contains a cysteine-rich domain that is involved in the formation of a homodimer to generate the ion channel . Thus, mutation of the cysteine-rich domain blocks the ion conductivity by the 3a protein . To this end, we substituted amino acids Cys-127, Cys-130, and Cys-133 within the cysteine-rich domain of the SARS-CoV 3a protein with serine to generate a lentivirus expressing the ion Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Spike glycoprotein comprised of S1 and S2 subunits. The S1 subunit contains a signal peptide, followed by an N-terminal domain and receptor-binding domain , while the S2 subunit contains conserved fusion peptide , heptad repeat 1 and 2, transmembrane domain , and cytoplasmic domain . We found that the S2 subunit of 2019-nCoV is highly conserved and shares 99% identity with those of the two bat SARS-like CoVs and human SARS-CoV . Thus the broad spectrum antiviral peptides against S2 would be an important preventive and treatment modality for testing in animal models before clinical trials . Though the S1 Title: Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides\nPassage: with the potential for the highest in situ binding affinities. These correspond to DENV-2 strain S1 E protein amino acids 41-60, 131-150, 251-270, and 351-370 that were selected for synthesis and antiviral testing .", "Title: Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II\nPassage: The median initial reproduction rate across all 51 outbreaks was 2 with a range of 0 to 38 . About half had an initial R of 1 or less, and over two-thirds had an initial R of 3 or less. The median duration, as measured by number of generations, was 1 with a range of 0 to 9 . About a third did not extend beyond the index generation, and nearly three quarters lasted for 3 or fewer generations. The median outbreak size, as measured by the total number of cases, was 4 with a range of 1 to 134 Title: Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II", "Passage: The median initial R across the 30 detailed outbreaks was 2 with a range of 0 to 38 . About a third had an initial R of 1 or less, and about two thirds had an initial R of 3 or less. Outbreaks that remained in the community had a lower initial R than those that were hospital based from the first generation . Mixed outbreaks, which generally started in the community and later spread through hospital contacts, had an intermediate initial R . The initial R was smaller when the index case had a typical versus atypical or hemorrhagic Title: Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II", "Passage: Outbreaks with greater initial R-values tended to be larger and longer. For example, in outbreaks with an initial R of 5 or less versus more than 5, median values for the total number of cases and generations were 2 versus 23 and 1 versus 2.5 respectively. Title: Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II", "Passage: Finally, the outbreak from Kosovo deserves notice because this region is not as developed or as wealthy as most of the other countries studied. This outbreak was the largest identified for this review . Moreover, the hospital and mixed component of this outbreak had the second highest and highest initial reproductive rate, and the hospital component lasted 9 generations . This suggests that a smallpox outbreak in a less developed country with limited resources for healthcare, disease surveillance, and case isolation could be potentially more devastating than a bioterrorist attack in a Western/industrialized country .", "Title: Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry\nPassage: primer pairs targeting NP and PB2 segments. All primers used in this study had a thymine nucleotide at the 59 end to minimize addition of non-templated adenosines during amplification using Taq polymerase . The sensitivity of each RT-PCR primer pair was determined using known quantities of a synthetic calibrant RNA template as described previously . Each of the primer pairs was sensitive to as few as twenty copies of the calibrant RNA and several primers were sensitive to five copies . Title: Multiplex primer prediction software for divergent targets", "Passage: : 1, 100 : 1, 1000 : 1 and 10000 : 1. These correspond to copy number ratios of vaccinia:human genomes of 1. All PCR experiments were analyzed on 3% agarose TBE gels containing ethidum bromide that were purchased from Bio-Rad . Blue juice TM 10\u00c2 loading dye was purchased from Invitrogen and diluted to 2\u00c2 before use. A 50-bp DNA ladder was purchased from Novagen . For analysis, 15 ml from each separate 25 ml PCR reaction were combined with 2 ml of of loading dye and 15 ml of the loading-dye/product mixture was loaded per well and electrophoresed Title: Multiplex primer prediction software for divergent targets", "Passage: acids could be problematic for universal viral priming using primers shorter than 15 bases, particularly for multiplexes of 10 or more primers. Nanda et al. were able to achieve sufficient viral isolation from cell culture samples to allow viral identification using viral PCR with priming sequences as short as pentamers, so the problem of contaminating host nucleic acids for specific, short primer PCR of viruses is not insurmountable. They found specific pentamer PCR to be several logs more sensitive than nonspecific amplification, provided that they purified encapsidated viral nucleic acids prior to PCR. Another method that has been used for Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase", "Passage: Oligonucleotides design. Primers were designed using the Primer Premier 5.0 program. Like a TaqMan probe, the HFman probe was designed in general with a fluorophore and a quencher at 5\u2032 and 3\u2032 end, respectively; however, a better form of the HFman probe is to have a 3\u2032 fluorophore and a 5\u2032 quencher. All primers were synthesized commercially by Thermofisher scientific . The detailed information of the primers, TaqMan and HFman probes are shown in Supplementary Tables S1 and S2.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: naturally occurring pattern following the evolutionary characteristics typical of CoVs, it is highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species are the most revealing signs that SARS-CoV-2 evolved by natural evolution. A search for an intermediate animal host between bats and humans is needed to identify animal CoVs more closely related to human SARS-CoV-2. There is speculation that pangolins might carry CoVs closely related to SARS-CoV-2, but the data to substantiate this is not yet published . Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Evolution is stepwise and accrues mutations gradually over time, whereas synthetic constructs would typically use a known backbone and introduce logical or targeted changes instead of the randomly occurring mutations that are present in naturally isolated viruses such as bat CoV RaTG13. In our view, there is currently no credible evidence to support the claim that SARS-CoV-2 originated from a laboratory-engineered CoV. It is more likely that SARS-CoV-2 is a recombinant CoV generated in nature between a bat CoV and another coronavirus in an intermediate animal host. More studies are needed to explore this possibility and resolve the natural origin Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity . Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Currently, there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin. Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV was recently reported, which shared \u223c96% homology with the SARS-CoV-2 . However, as we know, the human SARS-CoV and intermediate host palm civet SARSlike CoV shared 99.8% homology, with a total of 202 single-nucleotide variations identified across the genome . Given that there are greater than 1,100 nt differences between the human SARS-CoV-2 and the bat RaTG13-CoV , which are distributed throughout the genome in a", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Prior to December 2019, 6 CoVs were known to infect human, including 2 \u03b1CoV and 4 \u03b2CoV (HCoV-OC43 [ Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: infections and 800 deaths, and Middle East respiratory syndrome CoV which has caused a persistent epidemic in the Arabian Peninsula since 2012 . In both of these epidemics, these viruses have likely originated from bats and then jumped into another amplification mammalian host for SARS-CoV and the dromedary camel for MERS-CoV] before crossing species barriers to infect humans. Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: The SARS epidemic began quietly at the turn of the 21st century. In November 2002, a cook in Guangdong Province, China, died from an unidentified illness. He had worked at a restaurant in which meat from wild animals was served. On 27 November 2002 Chinese-language media and internet reports were picked up by Canada's Global Public Health Intelligence Network that indicated a flu-like illness was occurring in China . Unfortunately, the reports were not translated, and China failed to report the occurrence of this illness to the World Health Organization until February 2003. The disease spread to other countries where Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Since that first report, a slow discovery process over the following two to three years revealed a virus that had infected over 90 % of adult dromedary camels in the KSA , also DCs across the Arabian Peninsula and parts of Africa that are a source of DC imports for the KSA . To date, MERS-CoV has not been detected in DCs tested in zoos or herds from other parts of the world . Occasionally, virus is transmitted from infected DCs to exposed humans. Subsequent transmission to other humans requires relatively close and prolonged exposure . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV RNA has also been detected in DC samples, and recovery of infectious virus has also been achieved from DC samples . From some of these, full or majority length genomes of MERS-CoV have been sequenced . DC versions of MERS-CoV were found to be as similar to each other, as were variants detected from different humans over time and across distance.", "Title: How necessary is a fast testkit for mitigation of pandemic flu?\nPassage: Diagnosis is an important component in the overall pandemic management framework. With proper diagnosis, potential flu carriers can be identified before they become symptomatic. Non-pharmaceutical measures such as quarantine and contact tracing can then be activated, thus maximizing the probability of containment . Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: Current influenza diagnostic tests, especially when the strains are evolving constantly, vary differently in terms of efficiency, specificity and sensitivity . These factors will impact the intervention policies that should be made during an outbreak. It has been argued that a slow, low throughput laboratorybased diagnostic test, such as immunofluorescence DFA antibody staining and RT-PCR , may not be able to effectively assist pandemic mitigation . Ideally, a rapid PCRbased diagnostic testkit should be able to detect the relevant virus in less than 30 minutes, requiring nothing more than a patient sample, and a portable device to perform extraction and Title: Estimating the number of infections and the impact of non-\nPassage: underreporting as well as systematic and country-specific changes in testing. Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: both attack rates and costs through the implementation of policies involving full contact tracing and prophylaxis to the contacts will most probably be more significant.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The 2019 novel coronavirus , a betacoronavirus, forms a clade within the subgenus sarbecovirus of the Orthocoronavirinae subfamily . The severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus are also betacoronaviruses that are zoonotic in origin and have been linked to potential fatal illness during the outbreaks in 2003 and 2012, respectively . Based on current evidence, pathogenicity for 2019-nCoV is about 3%, which is significantly lower than SARS-CoV and MERS-CoV . However, 2019-nCoV has potentially higher transmissibility than both SARS-CoV and MERS-CoV . Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Is 2019-nCoV infection severe? To date approximately 14% of cases of 2019-nCoV have been described as severe by WHO, with a case-fatality rate of 2.1%.10 Estimates of severity are usually higher in the beginning of an epidemic due to the identification of the most severely affected cases and decline as the epidemic progresses. However, because many infected persons have not yet recovered and may still die, the case-fatality rate and severity could be underestimated. On January 30, 2020, WHO officially declared the 2019-nCoV epidemic as a Public Health Emergency of International Concern, indicating its concern that countries aside from China Title: Note from the editors: novel coronavirus (2019-nCoV)", "Passage: cases are being reported on a daily basis and there is evidence for some human-to-human transmission in China, a number of important questions remain unanswered. For example, there is no certainty about the source of the outbreak, the transmissibility of the virus as well as the clinical picture and severity of the disease. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5", "Title: Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection\nPassage: HRV-Ca strains. Kiang et al. have identified five novel HRVs out of 24 clinical samples , which segregated from HRV-A and HRV-B, and were classified as HRV-C, and three additional strains that also clustered with QPM, C024, C025, C026, NAT001 and NAT045 . However, the field HRV strains of these previous studies were sequenced using a 59UTR that did not match fully our sequence and that of Lee et al. , and could not be included in the present study for comparative analysis. Interestingly, the five strains identified in California in 2007 and N42 and N45 from our study were Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: We studied all data on SHCLCI from five influenza seasons in PIDIRAC sentinel network hospitals and made a comparative analysis of viral types and subtypes. The strain identified in > 50% of cases in each season was considered the predominant strain. Duration of hospital stay was divided into two categories < 10 days and 10 days or more. The statistical analysis was made using the Chi square test and Student's t test with 95% confidence intervals for continuous variables and the ANOVA test for categorical variables. Title: Spread of different rhinovirus B genotypes in hospitalized children in Spain", "Passage: found in China, 14 South Africa, 15 and the USA, 16 respectively. This lower diversity may be due to the number of years spanned in these studies -usually one or two -compared with our study of a 6AE5-year period. The most prevalent genotype in our study was the new clade 1, detected in six patients, followed by serotypes 6 and 35, detected in four patients each. On the contrary, in the mentioned surveys, HRV-B52 was the most prevalent serotype which was not detected in our study. Other serotypes detected were HRV-B27, HRV-B83, HRV-B6, and HRV-B4, all of them also detected Title: Genetic diversity of the 2013\u201314 human isolates of influenza H7N9 in China\nPassage: four viruses, which were isolated within the short period of just two months, all derive from the same local pool of influenza H7N9 strains that were circulating among avian species at that time.", "Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection\nPassage: NS4B . It is thus conceivable that inhibitors targeting TMD of NS4B would perturb its function, leading to the suppression of viral RNA replication. In this study, the replacement of Q130 of NS4B with a basic amino acid conferred the resistance effect without suppressing JEV replication, suggesting that position 130 could tolerate a basic amino acid and that the basic amino acid might be involved in the interplay of NS4B with host proteins rather than viral proteins. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: NS4B . It is thus conceivable that inhibitors targeting TMD of NS4B would perturb its function, leading to the suppression of viral RNA replication. In this study, the replacement of Q130 of NS4B with a basic amino acid conferred the resistance effect without suppressing JEV replication, suggesting that position 130 could tolerate a basic amino acid and that the basic amino acid might be involved in the interplay of NS4B with host proteins rather than viral proteins. Title: In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1", "Passage: Neuraminidase has become the main target for drug design against influenza virus due to its highly conserved catalytic site and its essential role in influenza virus replication . Oseltamivir is an antiviral drug against neuraminidase that is useful for preventing viral replication in the last stage of the viral live cycle . It directly interacts with the catalytic residues of the neuraminidase catalytic site, while the framework residues stabilize the enzyme structure . Resistance to oseltamivir has already become a widespread phenomenon, and prediction of the neuraminidase structure shows that the resistance could be several times higher than resistance to Title: Progress of small molecular inhibitors in the development of anti-influenza virus agents", "Passage: NA is a viral enzyme that is made up of four identical subunits and is anchored to the membrane of the virus . NA plays a key role in the spreading of the virus. The terminal neuraminic acid residues of the glycoproteins of the newly formed virion progeny form glycosidic linkages with the neuraminic acid receptor on the host-cell surface; this glycosidic linkage is cleaved by NA, which thereby assists in the release of the virion progeny from the infected cells . Therefore NA is an attractive target for anti-influenza research, and inhibitors of NA containing a Neu core have", "Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically: Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: Significance and potential impact of the study To provide greater insight into social network structures in resource poor settings, we propose to study social contact patterns within schools and households and compare and contrast patterns in the urban and rural setting exhibiting different demographic, economic, and socio-cultural characteristics. This will provide key data for use in transmission dynamic models for common respiratory viral and bacterial infections such as RSV and S. pneumoniae that are the leading cause of childhood morbidity and mortality in the SSA setting. We also seek to answer the question how we can optimize study design to", "Title: Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype\nPassage: meiosis I or II. Aneuploidies and other chromosomal abnormalities are a common cause of birth defects and are associated with significant morbidity and mortality. The spectrum of phenotypes seen in each affected individual is clearly dependant on the particular chromosomal region concerned, although there is still a great deal of variability in the presentation of phenotypes. Title: Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype", "Passage: An example could be Turner syndrome, which is the only whole chromosome monosomy that is viable in humans, with approximately 1 in 2,000 female births having one copy of the X chromosome . In addition to the main features of short stature and ovarian failure, present in almost all cases, there are many other phenotypes that may present, including a short webbed neck, kidney malformations, hearing problems and various learning difficulties, as well as increased risk of type 1 diabetes . It is possible that the extensive copy number variation on the X chromosome-37.8% according to the DGV -may contribute Title: Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype", "Passage: Using Down's Syndrome as an example, an extra copy of chromosome 21 is not sufficient to cause the full range of phenotypes associated with this disorder, as individuals can present with a range of sub-phenotypes. Some features are almost always present, such as the characteristic facial appearance and mental retardation, although these can vary widely in the severity of their presentation . Other features, however, are only present in a fraction of DS cases: for example, congenital heart defects are present in *40% of cases and gastrointestinal defects in *8% of DS . Leukaemia is also common in DS, with Title: Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype", "Passage: an *20% increased risk of acute lymphoblastic leukaemia , and transient myeloproliferative disorder occurring in *10% of DS newborns, of which 10-20% develop acute megakaryoblastic leukaemia before the age of 4 . A detailed knowledge of the genes on the affected chromosome is required to understand the phenotypic effects of aneuploidy. In addition, it is important to determine the overall effects of gene dosage imbalance, which may also be complex. Individuals with partial trisomy 21 resulting from unbalanced chromosomal translocations will only exhibit those features associated with the extra genomic material present. Molecular analysis of these patients enables 'phenotypic mapping'", "Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells\nPassage: Here, we focused on IFITM5, which is also known as bonerestricted IFITM-like protein . Among the IFITM family proteins, IFITM5 is unique. Expression of IFITM5: Unlike the other IFITM family proteins, the expression of IFITM5 is not induced by interferons because the region upstream of the ifitm5 gene lacks the interferon regulatory elements . Furthermore, the expression of IFITM5 is mostly restricted to osteoblast cells , while the other IFITM proteins are expressed ubiquitously . Amino-acid sequence similarity: The amino acid sequence of IFITM5 is relatively dissimilar to IFITM1-3 proteins , while IFITM1-3 proteins share ~ 85% similarity with each Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: Here, we focused on IFITM5, which is also known as bonerestricted IFITM-like protein . Among the IFITM family proteins, IFITM5 is unique. Expression of IFITM5: Unlike the other IFITM family proteins, the expression of IFITM5 is not induced by interferons because the region upstream of the ifitm5 gene lacks the interferon regulatory elements . Furthermore, the expression of IFITM5 is mostly restricted to osteoblast cells , while the other IFITM proteins are expressed ubiquitously . Amino-acid sequence similarity: The amino acid sequence of IFITM5 is relatively dissimilar to IFITM1-3 proteins , while IFITM1-3 proteins share ~ 85% similarity with each Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: Amino-acid sequence alignment of IFITM5, IFITM1, IFITM2, and IFITM3 derived from mice. The conserved residues are highlighted in black. The three conserved cysteines are highlighted in red and numbered based on the sequence of IFITM5 and IFITM3 . The residues unique in IFITM5 are highlighted in gray. The first and the second transmembrane domains, the extracellular sequences, and the cytoplasmic loop are indicated by arrows and denoted as TM1 and TM2, EC, and the CP loop, respectively. The TM domains were predicted by SOSUI. The aspartates at the C-terminal region in IFITM5 are shown in blue. B) The schematic illustration Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: Amino-acid sequence alignment of IFITM5, IFITM1, IFITM2, and IFITM3 derived from mice. The conserved residues are highlighted in black. The three conserved cysteines are highlighted in red and numbered based on the sequence of IFITM5 and IFITM3 . The residues unique in IFITM5 are highlighted in gray. The first and the second transmembrane domains, the extracellular sequences, and the cytoplasmic loop are indicated by arrows and denoted as TM1 and TM2, EC, and the CP loop, respectively. The TM domains were predicted by SOSUI. The aspartates at the C-terminal region in IFITM5 are shown in blue. B) The schematic illustration", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations", "Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: A total of 39,329 records were identified by the PubMed/MEDLINE search , and 39,305 articles met the study inclusion criteria after 24 records had been excluded . Table 2 details the general characteristics of the articles. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: The number of articles increased exponentially over the period 1965-2017 . Approximately 60% of the articles have been published since 2000. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis", "Passage: The evolution of RCTs has been an enduring and continuing process . Since the 1970s the publication landscape for RCTs has exhibited an exponential growth. For example, a 1965-2001 bibliometric analysis of the literature identified 369 articles published in 1970 compared to 11,159 published in 2000 . The development of clinical trial registries , the exponential increase in journals publishing trial protocols, results and secondary studies, and growing support for data-sharing policies have created an open research environment of transparency and accountability. Furthermore, the publication of reporting guidelines have served to facilitate the transition between research and reporting to ensure Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: 9, 2019.", "Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case\nPassage: temperature of 40.3uC, had infiltration of lower left lung lobe based on chest radiography, bilateral lower lung moist rales, and substantially reduced oxygen saturation. He was placed on a ventilator and treated with antibiotics, spasmolysis, corticosteroids, and the dissipatation of phlegm and fluids. Despite treatment, the patient presented with function damage of multiple organ on the second day after admission, and died 59 h after admission, and 8 days after the onset of symptoms. Throat swabs were collected and performed RT-PCR and rRT-PCR detection at the day patient died. No antiviral drug treatment was given since the patient died before Title: Retrospective diagnosis of a famous historical figure: ontological, epistemic, and ethical considerations", "Passage: original case report was short and did not have all the important elements that I discussed above. Title: Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report\nPassage: A forty year-old male was brought to the Queen Elizabeth Hospital, Kota Kinabalu, Sabah in a state of collapse. He was unable to give a history himself or to stand. On examination his blood pressure was unrecordable and oxygen saturations were recorded as low. Title: Fatal varicella pneumonia in an unvaccinated child with Down Syndrome: a case report\nPassage: The next day, the respiratory condition didn't improve and a new CXR showed an impairment of the spread, and a massive pulmonary hemorrhage. In the absence of recovery of the main indicators of organ perfusion, she was declared dead.", "Title: Detection of Common Respiratory Viruses and Mycoplasma pneumoniae in Patient-Occupied Rooms in Pediatric Wards\nPassage: Viral infections of the respiratory system are very common. In Taiwan, the predominant viruses isolated from patients with respiratory infections are enterovirus, respiratory syncytial virus , influenza A and B viruses, adenovirus, cytomegalovirus, herpes simplex virus-1, and parainfluenza virus. 27 Enterovirus causes herpangina, hand-foot-and-mouth disease, myocarditis, encephalitis, and death. RSV is the most common pathogen of the lower respiratory tract in infants 28 and a common cause of nosocomial infections in pediatric wards. 29 Influenza A and B viruses cause seasonal epidemics in Taiwan, especially in winter. 30 Adenovirus causes acute respiratory tract infections in children younger than 5 years Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: We also compared and contrasted the clinical and community results. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses found in the clinical sample. These three infections resulted in 41 viruses detected in 15 subjects clinically, and eight infections detected in five people in the community. Together they infected 94% of clinical subjects, and 7% in the community . The most common virus detected in community samples was Coronavirus OC43; this virus was detected in 13.3% people in the community and not in any of the clinical samples. However a different strain, coronavirus OC 229 Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: countries . In the developed world, viruses are already the most common pathogens causing diarrhea . Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond", "Passage: Rotavirus infection is the most common cause of viral gastroenteritis among children; however, parents of infected children also often become ill and as a result rotavirus is the second most common cause of gastroenteritis in adults . Studies in human volunteers have shown that infection with rotavirus causes diarrhea, results in shedding of the virus and a rise in antibody anti-virus titer after infection . Additionally, astroviruses infections are common, accounting for about 10% of all sporadic diarrhea cases . Astrovirus has been isolated from diseased people, filtrated and administered to healthy individuals after which in some of the volunteers", "Title: New aspects in the management of pneumonia\nPassage: The main side effects associated with corticosteroids, especially with prolonged use, are hyperglycemia, myopathy, weight gain, brushing, and osteopenia . As well as these side effects, corticosteroids have strong immunosuppressive effects, raising concerns regarding their use in acute infections, despite their potential effect in controlling excessive inflammatory response. The immunosuppressant effect of corticosteroids is related to dose and treatment duration. For example, the use of 40 mg of prednisolone per day for more than 1 week or 20 mg prednisolone or equivalent per day for a month can produce immunosuppression. In acute infection, a low dose for a short period Title: New aspects in the management of pneumonia", "Passage: Glucocorticosteroid drugs reproduce effects similar to endogenous cortisol: they have anti-inflammatory activity by switching genes on and off, resulting in a reduction of inflammatory cytokines and chemokines. Corticosteroids have an effect on structural cells of the respiratory tract: they act on epithelial cells by inhibiting transcription factors such as NF-kB, on mucous glands by decreasing mucus secretion, and on smooth muscle cells by increasing \u03b22 receptors . Title: Key mechanisms governing resolution of lung inflammation", "Passage: Despite ongoing controversy, glucocorticoids remain the best studied anti-inflammatory strategy in ARDS. There is some evidence to suggest that given early in disease course, intravenous steroids reduce requirement for mechanical ventilation, length of ITU stay and improve oxygenation, with a modest effect on mortality . Such success is, however, only likely to outweigh potential complications in the setting of vigilant surveillance for nosocomial infection and eschewal of neuromuscular blockade due to the potential complications of steroid treatment. Furthermore, it has been suggested that if left to later time points, i.e. >14 days postonset, steroid administration may cause a paradoxical increase Title: New aspects in the management of pneumonia\nPassage: may be useful for reducing inflammation and may not cause so much harm by producing immunosuppression. Moreover, a short period of corticosteroid treatment may reduce the risk for side effects.", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: . Pneumonia deaths decreased from 1.8 million in 2000 to 900,000 in 2013 . These data do not reflect the full impact of increasingly widespread use of pneumococcal conjugate vaccine in low-and middle-income countries because the incidence of pneumonia and number of deaths are likely to decrease still further as a result of this widespread intervention . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The overall burden of childhood pneumonia has been reduced substantially over the last decade, despite an increase in the global childhood population from 605 million in 2000 to 664 million in 2015 . Recent data suggest that there has been a 25% decrease in the incidence of pneumonia, from 0.29 episodes per child year in low-and middle-income countries in 2000, to 0.22 episodes per child year in 2010 . This is substantiated by a 58% decrease in pneumonia-associated disability-adjusted life years between 1990 and 2013, from 186 million to 78 million as estimated in the Global Burden of Disease study Title: Economic burden of pneumococcal infections in children under 5 years of age", "Passage: The resulting national economic burden is approximately 1 million Euros for pneumococcal meningitis, approximately 209 million Euros for pneumonia, and approximately 293 million Euros , indirect cost , and total cost were significantly higher in pneumonia patients aged 36 months than those aged <36 months . Direct cost of AOM was significantly higher in the patients aged <36 months than those aged 36 months . On the other hand, comparison of costs between genders revealed no difference between the groups . Title: Economic burden of pneumococcal infections in children under 5 years of age", "Passage: According to the global epidemiological data, more than 90% of pneumonia-related deaths in children under the age of 5 years occur in 40 countries, with the highest mortality rates in India, Pakistan, Bangladesh, and Afghanistan. 7 When intercontinental distribution of pneumonia-related death is evaluated in this age group, sub-Saharan Africa and South Asia show similar distribution. 8 In Turkey, although detailed data about respiratory tract infections are limited, the Turkey Burden of Disease Study conducted between 2002 and 2004 by the Ministry of Health reported that the ratio of disability adjusted life years caused by respiratory tract infections were 13.4%", "Title: Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review\nPassage: Concerning NRSI combined, 52 meta-analyses included only cohort studies and 5 only prospective cohort studies; 46 meta-analyses combined cohort and case-control studies, and 23 included all types of NRSI. The other 67 meta-analyses included \"observational studies\" , \"prospective and retrospective studies\" , and only \"retrospective studies\" . Title: Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review", "Passage: literature of NRSI is difficult . However, a recent study found that for 32 % of the observational studies registered at ClinicalTrials.gov, unpublished results could be retrieved . In contrast, we found that many meta-analyses assessed reporting bias . Reviewers may have compensated for the absence of searching for grey Only cohort studies 18 34 52 Including also case-control studies 18 28 46 Including all types of NRSI 5 18 23 Other 28 39 67 \"Observational studies\" 6 22 28 \"Prospective and retrospective studies\" 11 12 23 \"Retrospective studies\" 11 5 16 Did not clearly report design for each study Title: Comparing the outcomes of different postgraduate year training programs in Taiwan\nPassage: All of the 314 trainees participated in the MCQ exam. They were divided into four groups according to their training program. Title: A Literature Review and Survey of Childhood Pneumonia Etiology Studies: 2000\u20132010", "Passage: We received 81 responses to the survey. A total of 65 studies were identified once we removed responses that did not meet our study criteria. Of the 16 studies excluded from analysis, the reasons for exclusion were the following: the study was not a pneumonia etiology study, the study did not include children less than five years of age or multiple responses were received describing the same study. Studies ranged in size from 12 to 27 778 pneumonia patients . Among the 65 pneumonia etiology studies, 41 countries were represented . There were 16 countries that reported multiple studies. Of", "Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication\nPassage: Vaccination against FIPV with an attenuated, temperature-sensitive strain of type II FIPV induces low antibody titre in kittens that have not been exposed to FCoV. However, there is considerable controversy on the safety and efficacy of this vaccine, since the vaccine contains type 2 strain, whereas type 1 viruses are more prevalent in the field . In addition, antibodies against FIPV do not protect infected cats but enhance the infection of monocytes and macrophages via a mechanism known as Antibody-Dependent Enhancement . Besides vaccines, several antiviral drugs such as ribavirin, 2 BioMed Research International interferons, and immunosuppressive drugs have been Title: Avipoxviruses: infection biology and their use as vaccine vectors", "Passage: In the poultry industry, prophylactic measures against FWPV are achieved primarily by vaccination with live FWPV or antigenically similar pigeonpox virus strains produced in CEF cells . In the past two decades, numerous outbreaks have been reported in vaccinated flocks, suggesting that vaccines used against the disease were not effective. In the United States a commercial FWPV vaccine was shown to be contaminated with REV and caused lymphoma among broiler chickens . It has been shown that sequences of REV have been integrated into the DNA of FWPV vaccines as well as in field FWPV isolates . The integration site Title: Protection against Foot-and-Mouth Disease Virus in Guinea Pigs via Oral Administration of Recombinant Lactobacillus plantarum Expressing VP1", "Passage: Although vaccines have been useful for controlling and even eradicating FMD from parts of the world since the early 1900s, the disease still infects millions of animals each year and remains the main sanitary barrier to the commerce of animals and animal products. Vaccination is the main prophylactic method of preventing FMDV infection. Many types of vaccines have been designed-almost entirely parenterally administered-including inactivated antigen vaccines, live attenuated vaccines, DNA vaccines, empty capsid vaccines and synthetic peptide vaccines . Inactivated virus vaccines can elicit high levels of neutralizing antibodies and offer efficacious protection against homologous serotypes . However, these vaccines Title: Viral vector-based influenza vaccines", "Passage: subtype, namely A . 95, 96 Although FPV vector vaccines expressing influenza viral antigens rarely have been used in non-avian species, FPV-HA was capable of inducing antibody responses in cats 97 and afforded protection in pigs when challenged with a lowpathogenic A influenza virus. 67", "Title: Viral vector-based influenza vaccines\nPassage: vaccination. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: Similarly, various viral vectors have been successfully tested for their capability to deliver heterologous vaccine antigens, and this generally results in the induction of strong CTL immune responses. In the veterinary field, there are numerous viral vector vaccines that are currently licensed for use in livestock and domesticated animals. These recombinant vaccines are based on both DNA viruses and RNA viruses -based vaccines to be used in horses against West Nile virus] . Based on the safety record in the veterinary field, many viruses have been studied for human use as a vector in vaccine development . Amongst them, YFV Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Other bacteria that were developed as DNA vaccine carriers include Listeria monocytogenes , Shigella spp. , and Yersinia enterolica . Title: Viral vector-based influenza vaccines\nPassage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The URT is a less invasive and more convenient sampling site however, and an oropharyngeal and throat swab or a nasopharyngeal aspirate/wash are recommended when URT sampling is to be conducted . Paired sera, collected two to three weeks apart are preferable for serological testing while a single sample is suggested to be sufficient if collected two weeks after onset of disease or a single serum collected during the first 10-12 days if conducting RT-rtPCR . Human urine and stool have been found to contain MERS-CoV RNA 12 to 26 days after symptom onset and are listed as samples that Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: should be considered . In two cases that arrived in the Netherlands, urine was RT-rtPCR negative but faeces was weakly positive and sera were RT-rtPCR positive for five days or more . The finding of MERS-CoV viral RNA in serum provides an avenue for retrospective PCR-based studies if respiratory samples are unavailable . RNAaemia may also correlate with disease severity; signs of virus were cleared from the serum of a recovered patient, yet lingered until the death of another . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Individual human case studies report long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms. In one instance, a HCW shed viral RNA for 42 days in the absence of disease . It is an area of high priority to better understand whether such cases are able to infect others. Over three quarters of MERS cases shed viral RNA in their LRT specimens for at least 30 days, while only 30 % of contacts were still shedding RNA in their URT specimens . Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "Passage: Unfortunately, in our study, we did not collect stool samples from patients and did not pursue viral RNA in the stool. But we believe the existence of virus RNA in the stool samples from these patients because that a large amount of viral RNA was detected in anal swabs and that viral RNA had also been detected in a case reported from the United States . Also, we didn't collect sputum and bronchoalveolar lavage fluid for virus detection because that the dry coughing characteristic of patients infected with 2019-nCoV prevents producing enough amount of sputum and that bronchoalveolar lavage fluid", "Title: Differential Response of Primary Alveolar Type I and Type II Cells to LPS Stimulation\nPassage: The alveolar epithelium is an important component of the innate immune response of the lung. By providing an anatomic barrier that separates the organism from the external environment, the alveolar epithelium serves as a first line of defense against potential inhaled pathogens. While the cells of the innate immune system, such as alveolar macrophages and dendritic cells, harbor the bulk of the responsibility for prompting an immune reaction upon encountering inhaled pathogens, the cells that comprise the alveolar epithelium have also been implicated in aiding to trigger an inflammatory response. Title: Epithelial Cells Derived from Swine Bone Marrow Express Stem Cell Markers and Support Influenza Virus Replication In Vitro", "Passage: Bone marrow cell therapy may be effective in conditions that currently lack effective treatment. Stem cells isolated from different anatomic niches of lungs have been shown to differentiate into multiple epithelial cell types following lung injury. Our lab and Wong and colleagues demonstrated the existence of progenitor epithelial cells in the bone marrow of pigs and humans respectively which are capable of differentiating into type I and II pneumocytes suggesting that these cells will be valuable for lung therapies. Functionally, type I pneumocytes are important for gas exchange, water permeability and the regulation of alveolar fluid homeostasis whereas type II Title: Epithelial Cells Derived from Swine Bone Marrow Express Stem Cell Markers and Support Influenza Virus Replication In Vitro", "Passage: endotoxin-induced lung injury . Following infusion of BMCs in animal models, these cells have been identified as type I and II alveolar epithelial cells, endothelial cells, fibroblasts, and bronchial epithelial cells . However, precise identity of specific subpopulation of BMCs that engraft in the lung parenchyma and have regenerative potential is still not clear. Title: Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia\u2014a new therapeutic strategy?", "Passage: Myeloid cells like monocytes, macrophages, dendritic cells , and their common precursor cells, summarized as mononuclear phagocytes, are crucial in driving IV clearance . Combining sensor and effector functions of innate immunity, the lung epithelium plays an important role in coordinating, maintaining, and balancing the phagocyte-mediated antiviral host response . The intimate spatial proximity of alveolar macrophages and the tissue-resident DC network with the distal lung epithelium provides an ideal basis for direct cell-cell communication. Mechanisms involved in this cellular crosstalk might represent potential targets for treatment.", "Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Secondly, the R0, the basic reproduction number, is correctly described as the average number of infections each case causes. But it lacks two key ideas: 1) the 0 after the R implies the native state, which is a fully susceptible population and without any control measures. R is the effectiive number and can include the impact of control measures. Title: The Failure of R (0)\nPassage: death rates from the corresponding ODE. Thus, in this case, R 0 does not signal epidemic growth as anticipated from other methods. Roberts noted three fundamental properties commonly attributed to R 0 : that an endemic infection can persist only if R 0 > 1, R 0 provides a direct measure of the control effort required to eliminate the infection, and pathogens evolve to maximise their R 0 value. Title: The Failure of R (0)", "Passage: What is urgently needed is a simple, but accurate, measure of disease spread that has a consistent threshold property and which can be understood by nonmathematicians. If R 0 is to be used, it must be accompanied by a declaration of which method was used, which assumptions are underlying the model and evidence that it is actually a threshold, with no backward bifurcation. Without such caveats, the concept of R 0 will continue to fail. Title: The Model Repository of the Models of Infectious Disease Agent Study\nPassage: infection of index cases and the secondary cases they produce. The R0 is a measure of the transmissibility of the strain in the population, and largely determines the proportion of the population that will be infected in a pandemic. The ratio R0/Tg is a measure of an epidemic's rate of growth.", "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: In an analysis of the first 425 confirmed cases of infection, 73% of cases with illness onset between 12 and 22 January reported no exposure to either a wet market or another person with symptoms of a respiratory illness . The lack of reported exposure to another ill person could be attributed to lack of awareness or recall bias, but China's health minister publicly warned that pre-symptomatic transmission could be occurring . Determining the extent to which asymptomatic or pre-symptomatic transmission might be occurring is an urgent priority, because it has direct implications for public health and hospital infection control. Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: For our work, we developed a stochastic agent-based pandemic model on a small-scale city. We extended the typical transmission model by adding a pre-symptomatic phase, thus resulting in the SEPIR model. In addition, we further refined the infectious phase into one of the three possible categories-asymptomatic, symptomatic and critical . To capture the constraints imposed by societal norms, such as the different population response patterns during different times of the day, we set the granularity of the time scale to be in terms of hours, rather than days. Title: Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting", "Passage: a long history of low numbers of cases. If our missing source of infections was mainly indigenous asymptomatic infections, it would signify that there is an asymptomatic reservoir contributing to onward transmission and that must be controlled to reach elimination. This could be achieved through PCR-based screening and treatment or increased vector control in focal areas. An alternative explanation is that there may be a small number of unreported symptomatic cases or relapse cases which were not reported or detected, which could be indigenous or imported. If due to importation this would further support the need for strong regional cooperation Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Those under 18 years are a critical group to study in order to tease out the relative roles of susceptibility vs severity as possible underlying causes for the very rare recorded instances of infection in this age group. Are children protected from infection or do they not fall ill after infection? If they are naturally immune, which is unlikely, we should understand why; otherwise, even if they do not show symptoms, it is important to know if they shed the virus. Obviously, the question about virus shedding of those being infected but asymptomatic leads to the crucial question of infectivity.", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Abstract: Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005\u201307 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: Text: Chikungunya virus , a mosquito-borne pathogen listed by National Institute of Allergy and Infectious Diseases as a Category C Priority Pathogen that causes Chikungunya fever , has been spreading throughout Asia, Africa, and parts of Europe in recent times . CHIKV is an arthropod-borne virus and is transmitted to humans primarily by Aedes aegypti, the infamous yellow fever propagator . CHIKV infection is marked by severe joint pain, contorting its victims into unusual postures . The disease gets its name from the Kimakonde vernacular language of Tanzania and Mozambique, and the word chikungunya means ''that which contorts or bends Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: vector similar to the ones observed in Reunion Island . Title: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity", "Passage: The Chikungunya virus , an arthropod-borne virus , is a single-stranded positive-sense RNA virus with three genotypes. The virus is of the Alphavirus genus in the Togaviridae family . CHIKV has been shown to infect and be transmitted by Ae. aegyptii and Ae. albopictus mosquitoes. It was identified in East Africa in the early 1950s and since then has caused epidemics in continental Africa, the Indian Ocean region, and countries of Southeast Asia such as India, where since 2006 suspected cases have been estimated to be 1.39 million, and Singapore . The only reported outbreak outside these areas was in", "Title: Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome\nPassage: Of the clinical manifestations, agitation, conjunctival hemorrhage, and coma were negatively correlated with the survival outcome . Of the HFRSrelated complications, cardiac failure, ARDS and encephalopathy were negatively correlated with the survival outcome, while ARF was positively correlated with the survival outcome . Of the laboratory parameters, WBC, PT and APTT were negatively correlated with the survival outcome, while Scr was positively correlated with the survival outcome . Title: Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome", "Passage: Laboratory and imaging results that documented the clinical presentations and outcomes of the critical patients with HFRS complicated by ARDS were analyzed and compared. Biochemical tests of blood samples were performed using an autoanalyzer , including basic metabolic, liver and renal function and glucose tests. Blood clotting functions were tested using hematology analyzers . Chest and abdomen organs were visualized using X-ray radiography and ultrasonography . Computed tomography was performed in some patients. Cardiac function was measured using Cardiofax and ultrasonography . Arterial blood gases were measured using an automatic blood gas system . Hemo cultures were tested using an Title: Study on expression of plasma sCD138 in patients with hemorrhagic fever with renal syndrome", "Passage: According to the HFRS criteria of clinical classification , the severity of HFRS was classified into four types: mild, defined as patients who had kidney injury without oliguria and hypotension; moderate, defined as patients who had uremia, effusion , hypotension, hemorrhage , and AKI with typical oliguria; severe, defined as patients who had severe uremia, effusion , hemorrhage , hypotension and AKI with oliguria for \u22645 days or anuria for \u22642 days; and critical, defined as patients who usually had one or more of the following complications compared with the severe patients: refractory shock , visceral hemorrhage, heart failure, pulmonary Title: Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome", "Passage: The medical charts of 356 typical HFRS patients who were treated in the Center for Infectious Diseases, Tangdu Hospital, between January 2008 and August 2012 were selected randomly and reviewed. The diagnosis of HFRS was made based upon the detection of specific IgM and IgG antibodies to HTNV in acute phase serum specimens by enzyme-linked immunosorbent assay .", "Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells\nPassage: Here, we focused on IFITM5, which is also known as bonerestricted IFITM-like protein . Among the IFITM family proteins, IFITM5 is unique. Expression of IFITM5: Unlike the other IFITM family proteins, the expression of IFITM5 is not induced by interferons because the region upstream of the ifitm5 gene lacks the interferon regulatory elements . Furthermore, the expression of IFITM5 is mostly restricted to osteoblast cells , while the other IFITM proteins are expressed ubiquitously . Amino-acid sequence similarity: The amino acid sequence of IFITM5 is relatively dissimilar to IFITM1-3 proteins , while IFITM1-3 proteins share ~ 85% similarity with each Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: Here, we focused on IFITM5, which is also known as bonerestricted IFITM-like protein . Among the IFITM family proteins, IFITM5 is unique. Expression of IFITM5: Unlike the other IFITM family proteins, the expression of IFITM5 is not induced by interferons because the region upstream of the ifitm5 gene lacks the interferon regulatory elements . Furthermore, the expression of IFITM5 is mostly restricted to osteoblast cells , while the other IFITM proteins are expressed ubiquitously . Amino-acid sequence similarity: The amino acid sequence of IFITM5 is relatively dissimilar to IFITM1-3 proteins , while IFITM1-3 proteins share ~ 85% similarity with each Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: The interferon-induced transmembrane protein family is a part of the dispanin family and is composed of double-transmembrane \u03b1-helices connected by a cytoplasmic loop and extracellular amino-and carboxyl-terminal polypeptide sequences . The IFITM proteins are evolutionarily conserved in vertebrates . Recent genomic research has revealed that there are 5 IFITM members in humans and 7 members in mice . These proteins play roles in diverse biological processes, such as germ cell maturation during gastrulation , cell-to-cell adhesion , antiviral activity , and bone formation , although the detailed functions of IFITM6, 7, and 10 are unknown at present. In particular, IFITM3 Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: to increase calcium uptake and bone nodule formation . Role of IFITM5 for immune activity: Recent studies have revealed that IFITM5 interacts with the FK506-binding protein 11 to form IFITM5-FKBP11-CD81-the prostaglandin F2 receptor negative regulator complex . When the complex is formed, the expressions of 5 interferon-induced genes are induced, including bone marrow stromal cell antigen 2 , interferon inducible protein 1 , interferoninduced protein with tetratricopeptide repeats 3 , bmicroglobulin , and MHC class I antigen gene. Consequently, these results indicate that IFITM5 is involved not only in the bone formation but also in the immune system activity.", "Title: A New Model for Hendra Virus Encephalitis in the Mouse\nPassage: bats have been identified as the reservoir host , however epidemiological evidence does not support direct bat to human transmission. Horses have been an intermediate host in the transmission of disease to humans in all cases. There are as yet no readily available effective therapies or prophylaxis for HeV infection, either for use in humans or other susceptible animals. Title: Molecular Phylogeny of Hantaviruses Harbored by Insectivorous Bats in C\u00f4te d\u2019Ivoire and Vietnam", "Passage: Mammalian reservoirs of zoonotic viruses typically do not display host restrictions within a given taxonomic order. Also, infection is usually chronic, persistent and subclinical. For example, rodents of multiple genera and species, belonging to four subfamilies in the order Rodentia, serve as reservoirs of hantaviruses in Eurasia, Africa and the Americas and do not exhibit clinical disease or survival disadvantage. In addition, recently, hantaviruses exhibiting far greater genetic diversity have been detected in healthy-appearing shrews and moles representing many genera in six subfamilies within the order Soricomorpha in Eurasia, Africa and North America. Similarly, as mentioned earlier, bat species belonging Title: Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France", "Passage: Hantaviruses are emerging zoonotic pathogens distributed worldwide except in Antarctica . They may cause two severe pathologies in humans: hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome . Viruses of the genus Hantavirus are exceptions within the Bunyaviridae family, in being directly transmitted via aerosols ofsmall mammals excreta with no role for arthropod vectors . Although a growing diversity of hantaviruses has been discovered over the last decade in insectivores and bats , up to now, only rodent-borne hantaviruses have been shown at the origin of human diseases. Hantaviruses are small, enveloped viruses, possessing a tri-segmented RNA genome of Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: Hantavirus is a virus transmitted mainly by rodent animals, mainly through urine, feces, and saliva and the aerosols produced by them, but rarely by the bites of infected animals . In recent years, the infection rate of hantavirus has increased in China and Europe . Hantavirus disease has turned out to be a newly identified but not a \"new\" disease in Germany . The clinical presentations may vary according to viral strains prevalence in different regions. In Asia, hantavirus infection by Hantan virus and Seoul virus targets mainly the human kidney and causes hemorrhagic fever with renal syndrome . In", "Title: Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells\nPassage: Influenza virus can cause acute and severe respiratory diseases. According to the WHO, about 3-5 million people are severely infected with influenza virus, and among those, 290,000-650,000 people die annually , 2017). Compared to most seasonal influenza viruses, pandemic influenza viruses prefer to infect lower respiratory airways and often cause severe lung disease, such as pneumonia and acute respiratory distress syndrome . The lower respiratory tract consists of the trachea, bronchi, bronchioles, and alveoli. Alveoli are the ends of the respiratory tree and act as the basic units of ventilation of the lung. The alveoli consist of an epithelial layer Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: Inoculation of RV happens either directly on the nasal mucosa or via the eye conjunctiva where it is transported via the lacrymal duct to the nasal cavity, and then on to the nasopharynx. The airway epithelium is the primary site of infection of RV and it was shown in studies of both natural and experimentally-induced cold that viral RNA cannot be detected in the subepithelial layer, only in epithelial cells. Most RV-A and -B utilize intercellular adhesion molecule -1 as cell entry receptor and the others alternatively bind low density lipoprotein receptor , whereas RV-C utilizes a different receptor molecule Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: Inoculation of RV happens either directly on the nasal mucosa or via the eye conjunctiva where it is transported via the lacrymal duct to the nasal cavity, and then on to the nasopharynx. The airway epithelium is the primary site of infection of RV and it was shown in studies of both natural and experimentally-induced cold that viral RNA cannot be detected in the subepithelial layer, only in epithelial cells. Most RV-A and -B utilize intercellular adhesion molecule -1 as cell entry receptor and the others alternatively bind low density lipoprotein receptor , whereas RV-C utilizes a different receptor molecule Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Respiratory viruses primarily infect and replicate within airway epithelial cells . During the replication process, the cells release antiviral factors and cytokines that alter local airway inflammation and airway niche . In a healthy airway, the inflammation normally leads to type 1 inflammatory responses consisting of activation of an antiviral state and infiltration of antiviral effector cells. This eventually results in the resolution of the inflammatory response and clearance of the viral infection . However, in a chronically inflamed airway, the responses against the virus may be impaired or aberrant, causing sustained inflammation and erroneous infiltration, resulting in the exacerbation", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Hantavirus infections became a concern in the Americas after the description of an outbreak of acute respiratory distress occurred in the Four Corners area in 1993 . The newly recognized disease, hantavirus cardiopulmonary syndrome, HCPS , was linked to infection by the newly-discovered Sin Nombre virus , and the rodent Peromyscus maniculatus was identified as the reservoir . However, hantavirus infections have a much longer history. A review of ancient Chinese writings, dating back to approximately 960 AD, revealed descriptions closely resembling hemorrhagic fever with renal syndrome , the syndrome caused by Old World hantaviruses . During the twentieth century, Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: of human hantavirus infections in Central America. In South America, the first largest identified outbreak occurred in the Chaco region in northwestern Paraguay during 1995-1996. Seventeen individuals were identified with SNV antibody or were antigen positive out of 52 suspected cases . Major outbreaks due to ANDV occurred in 1996 in southern Argentina ; in southern Chile clusters of patients presented with hantavirus illness in 1997 . In Brazil, the first outbreak was identified in the Brazilian Amazon in 2000, and involved small villages that resulted in a 13.3% prevalence of those tested . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Hantaviruses are horizontally transmitted between rodents and are not transmitted by arthropods . Spillover infection to nonhuman mammals usually results in no onward transmission, but if humans are infected may result in high morbidity and mortality . During the spring of 1993, an outbreak of patients with HCPS due to SNV occurred in the Four Corners states resulting in more than 60% case-fatality among the initial cases, many involving members of the Navajo tribe . In Panama, an outbreak was reported during 1999-2000 in Los Santos, and 12 cases where identified with three fatalities . This represented the first report Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: cases of acute febrile disease with renal compromise were described from several Eurasian countries and Japan, often in association with military engagements . HFRS as a distinct syndrome, however, was first brought to the attention of western medicine in association with an outbreak that occurred among United Nations troops during the Korean conflict between 1951 and 1954, where more than 3,200 soldiers were afflicted . It took more than two decades until the etiologic agent, Hantaan virus , was isolated from the striped field mouse Apodemus agrarius, detected in part by the binding of antibodies from patient serum samples to", "Title: Old World camels in a modern world \u2013 a balancing act between conservation and genetic improvement\nPassage: Female and male reproductive performances according to camel type were traced in three Indian dromedary populations . Several parameters, like conception rate, first service conception rate, percentage of infertile females, average number of services required per fertile female, pregnancy rate, sperm morphology and motility, and testosterone profiling, were shown to exhibit inter-type variability. The latest study on pregnancy and parturition in over 2100 dromedaries from six different breeds/ecotypes showed that the season and the female camel were the most important determinants of variation in gestation length and calf birth weight. Seasonal changes were independent of nutritional factors but associated with Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Camel calving season occurs in the winter months and this may be a time when there is increased risk to humans of spill-over due to new infections among na\u00efve DC populations . What role maternal camel antibody might play in delaying infection of calves remains unknown . Juvenile DCs appear to host active infection more often than adult DCs and thus the sacrificial slaughter of DCs, which must be five years of age or older , may not be accompanied by significant risk of exposure to infection. In contrast to earlier results, slaughterhouse workers who kill both younger and older Title: Old World camels in a modern world \u2013 a balancing act between conservation and genetic improvement", "Passage: representing seven different populations over a 5-year period, showing a strong influence of the respective dromedary types on all parameters. Furthermore, the milking performance of three Saudi dromedary types managed under the same conditions during a 10-month lactation period showed that camels achieved peak yields at the fourth month of lactation, whereas the total lactation yield and milk composition varied among the three populations . Title: Old World camels in a modern world \u2013 a balancing act between conservation and genetic improvement\nPassage: In some countries, mainly young males up to two years old are slaughtered for meat, whereas in other regions adults are preferred . These preferences have led to different fattening systems: extensive, pastoral fattening mainly used for adults, e.g. in Somalia and Ethiopia; and intensive fattening with feedlots for young camels as practised, for example, in Saudi Arabia, United Arab Emirates and Tunisia.", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: Our study results suggest that the following may be clinical features of ARDS caused by HAdV-55: persistent high fever, rapid progression of dyspnea, need for mechanical ventilation support, elevated AST level and rapid progression from unilateral infiltrates to bilateral consolidations. These clinical features are highly similar to those of ARDS caused by other types of HAdV described in previous reports . Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Our study results suggest that the following may be clinical features of ARDS caused by HAdV-55: persistent high fever, rapid progression of dyspnea, need for mechanical ventilation support, elevated AST level and rapid progression from unilateral infiltrates to bilateral consolidations. These clinical features are highly similar to those of ARDS caused by other types of HAdV described in previous reports . Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: together with bilateral consolidations and infiltrates at the same time, are the most frequent clinical manifestations of severe HAdV-55induced ARDS. Viral load monitoring may help predict disease severity and patient outcome. The NPPV and IMV failure rates were very high, and ECMO may be the last support method for this group of patients. HAdV-55-induced severe ARDS has a very high mortality rate despite appropriate respiratory support. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: together with bilateral consolidations and infiltrates at the same time, are the most frequent clinical manifestations of severe HAdV-55induced ARDS. Viral load monitoring may help predict disease severity and patient outcome. The NPPV and IMV failure rates were very high, and ECMO may be the last support method for this group of patients. HAdV-55-induced severe ARDS has a very high mortality rate despite appropriate respiratory support.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Recently, Esvelt et al. developed a novel strategy for directed evolution of filamentous phage-displayed proteins, called phage-assisted continuous evolution , which allows multiple rounds of evolution per day with little experimental intervention. The authors engineered M13 phage to encode an exogenous protein , whose functional activity triggers gene III expression from an accessory plasmid; variants of the exogenous protein arise by random mutagenesis during phage replication, the rate of which can be increased by inducible expression of error-prone DNA polymerases. By supplying limiting amounts of receptive E. coli cells to the engineered phage variants, Esvelt et al. elegantly linked phage Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Recently, Esvelt et al. developed a novel strategy for directed evolution of filamentous phage-displayed proteins, called phage-assisted continuous evolution , which allows multiple rounds of evolution per day with little experimental intervention. The authors engineered M13 phage to encode an exogenous protein , whose functional activity triggers gene III expression from an accessory plasmid; variants of the exogenous protein arise by random mutagenesis during phage replication, the rate of which can be increased by inducible expression of error-prone DNA polymerases. By supplying limiting amounts of receptive E. coli cells to the engineered phage variants, Esvelt et al. elegantly linked phage Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis", "Title: CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial\nPassage: The trial commenced recruiting patients in February 2013 and by the end of May 2014 had recruited 357 patients. Two interim analyses were made by an independent data monitoring and ethics committee, as predetermined, and on both occasions, it was concluded that the trial was being conducted well, and should continue. An investigators' meeting was held in Vietnam to develop the collaborative network, share best-practice qualities, discuss recruitment strategies, and consider opportunities for substudies. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: The 8-week pilot study will take place from January to April 2007. The exact starting and stopping dates of patient recruitment will not be fixed in advance. Recruitment will begin after the start of the annual influenza peak season has been confirmed by the Department of Microbiology, HKU, and will continue until the prespecified sample size is reached. The 39-week main study will take place from January to September 2008. Title: CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial", "Passage: Event-driven stopping of the trial after 247 observed deaths is not foreseen even if this should occur prior to recruiting 880 patients. Thus, the study will be conservatively powered if the study mortality is larger than 30%. For example, if overall mortality was around 50% and 412 deaths were observed during the study, power would increase to 95% for a true hazard ratio of 0.7 and to 83% for a true hazard ratio of 0.75. Title: CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial", "Passage: Selected study members will be trained on how to enter all clinical data as source information from the CRFs and from laboratory source documents into an Internet-based computerised dataentry system called CliRes hosted by OUCRU Viet Nam. Data entry will occur simultaneously, as data are being generated during the trial as soon as possible after the information is generated. Data may be manually entered or scanned and electronically uploaded, dependent on available software. Source documents and electronic data will be verified according to the Trial Monitoring Plan.", "Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: We also compared and contrasted the clinical and community results. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses found in the clinical sample. These three infections resulted in 41 viruses detected in 15 subjects clinically, and eight infections detected in five people in the community. Together they infected 94% of clinical subjects, and 7% in the community . The most common virus detected in community samples was Coronavirus OC43; this virus was detected in 13.3% people in the community and not in any of the clinical samples. However a different strain, coronavirus OC 229 Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% of clinical subjects, and 6.7% of community subjects . Coronavirus OC43 was the most common virus detected in community members . A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: and strains of circulating viruses. Also, because PCR was used for viral detection, the study was limited to detection of viruses in the primer sets. Given that these are the most up-to-date and common viruses, this approach was deemed sufficient for this initial investigation. Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Abstract: OBJECTIVE: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical surveillance in Nigeria. RESULTS: Children were selected via convenience sampling from communities and a tertiary care center during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority of subjects were under 6 years old, of whom 46 were infected . A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The NYVAC vector is a highly attenuated vaccinia virus strain. NYVAC is replication-restricted; however, it grows in chick embryo fibroblasts and Vero cells enabling vaccine-scale production. In non-permissive cells, critical late structural proteins are not produced stopping replication at the immature virion stage . NYVAC is very attenuated and considered safe for use in humans of all ages; however, it predominantly induces a CD4 + T cell response which is different compared to MVA . Both MVA and NYVAC provoke robust humoral responses, and can be delivered mucosally to induce mucosal antibody responses . There has been only limited exploration Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is strong safety and efficacy data for use of NYVAC or MVA-vectored influenza vaccines, preexisting immunity remains a concern. Although the smallpox vaccination campaign has resulted in a population of poxvirus-na\u00ef ve people, the initiation of an MVA or NYVAC vaccination program for HIV, influenza or other pathogens will rapidly reduce this susceptible population. While there is significant interest in development of pox-vectored influenza virus vaccines, current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains. This would likely limit the use and/or efficacy of poxvirus-vectored influenza virus vaccines for regular and seasonal use Title: Virus-Vectored Influenza Virus Vaccines", "Passage: . Intriguingly, NYVAC may have an advantage for use as an influenza vaccine vector, because immunization with this vector induces weaker vaccine-specific immune responses compared to other poxvirus vaccines, a feature that may address the concerns surrounding preexisting immunity . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2 . Poxviruses are also studied extensively as candidate vectors for human use, among which attenuated derivatives of vaccinia virus and New York attenuated vaccinia virus NYVAC strains] are the most promising vectors . They are ideal candidate vectors due to their large DNA-packing capacity and their thermal and genetic stability . The NYVAC vector has been shown to induce CD4 + T cell-dominant responses, and MVA induces", "Title: Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques\nPassage: Human adenoviral vector-based vaccines expressing HIV-1 or SIV antigens have been shown to induce potent HIV-1 or SIV-specific T-cell responses in the periphery and at mucosal sites . However, vaccination regimens using a replication-defective adenovirus serotype 5 vector , alone or in prime-boost with DNA, did not reduce HIV-1 acquisition rates or set-point viral loads in clinical trials . Both CD4 + and CD8 + T-cell responses were detected in the vaccinees, with a predominance of CD8 + T-cell responses. Whether the insufficient magnitude, functionality or breadth of the vaccine-induced cellular immune responses participated in the failure of the Ad5 Title: Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses", "Passage: Like many infectious diseases that have had significant impact on the human population, a vaccine against HIV is critically needed. Along with humoral immunity, CD8 + T cells have been shown to be important in the control of HIV . Cellular immunity induced in the Ad5-STEP trial failed to protect individuals from HIV, resulting in more people from the vaccine group acquiring infection compared to the placebo . Part of the problem was thought to be the presence of preexisting immunity against the vector . The NSVs used in this study were chosen, because few individuals have preexisting immunity. Title: Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques", "Passage: vaccine to provide demonstrable protection against HIV-1 infection remains unclear. In particular, in the 'STEP' clinical trial, pre-existing Ad5-specific antibody titers appeared to have negatively impacted the HIV-1-specific CD8 + T-cell responder rate after vaccination . Title: Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques\nPassage: While no F4/AS01-induced CD8 + T-cell responses were observed in our experiments in the NHP model , such responses were observed in CB6F1 mice. After vaccination, HIV-1 specific cytokine-expressing CD4 + and/or CD8 + T cells were detected in each compartment assessed, with the highest frequencies found in the genital tract mucosa . No CD4 + or CD8 + T-cell responses were detected in the control group.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: On this occasion information sharing seems to have been rapid and effective . The WHO was notified of the original clustering within days and the full genomic sequence of the new virus was published less than 2 weeks after the cluster was first detected. The WHO has expressed its satisfaction with the actions of the Chinese authorities in sharing information with the WHO. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The complete genome sequence of 2019-nCoV HKU-SZ-005b was available at GenBank . The representative complete genomes of other related \u03b2CoVs strains collected from human or mammals were included for comparative analysis. These included strains collected from human, bats, and Himalayan palm civet between 2003 and 2018, with one 229E coronavirus strain as the outgroup. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: DOI: 10.1080/22221751.2020.1719902", "Title: Neutrophil heterogeneity and its role in infectious complications after severe trauma\nPassage: After trauma, the injury induces an immediate innate immune response to protect disrupted barriers from pathogens, to clear tissue damage, and to induce healing . Many humoral and cellular mediators including leukocytes, the coagulation, and complement cascades strictly regulate these processes. However, sometimes these processes become dysregulated and severe immune mediated complications can occur . Neutrophils are the most abundant leukocytes of all innate effector cells, and the first responders to tissue damage and invading pathogens . These cells are able to internalize and kill microbes, as well as to perform tissue debridement and attract monocytes to initiate healing . Title: Neutrophil heterogeneity and its role in infectious complications after severe trauma", "Passage: After trauma, neutrophils help to resolve tissue damage and to form a sufficient defense against bacteria by phagocytosis, release of antimicrobial molecules through degranulation, and the release of neutrophil extracellular traps . Antimicrobial molecules include proteases and reactive oxygen species . These molecules are essential for bactericidal activity, but can also contribute to collateral organ damage of the host when released into tissues . At the same time, disrupted protective barriers in combination with the presence of immunosuppressive neutrophils and less responsive neutrophils , enhance the susceptibility to post-traumatic infections. The knowledge that there are less responsive and immunosuppressive neutrophils Title: Neutrophil heterogeneity and its role in infectious complications after severe trauma", "Passage: Therefore, neutrophils are known to play a key role in the post-traumatic immune response . Moreover, neutrophils do not only sense and clear molecular danger but also respond to many soluble factors and it is likely that neutrophils therefore represent the cumulative effect of these factors . Hence changes in neutrophil phenotype could be one of the most accurate monitoring opportunities of the immune system currently available. Several reviews focused on neutrophils and post-traumatic complications . Since then, however, new data on the post-traumatic immune response and the role of neutrophils in the development of infectious complications have become available. Title: Neutrophil heterogeneity and its role in infectious complications after severe trauma", "Passage: immune response can potentially avert inflammatory complications, but should not be used liberally because the immune response is tightly regulated and inappropriate use of such treatments could lead to further deterioration. It is tempting to speculate that clinicians could use neutrophil immune monitoring to select those patients who would benefit from neutrophil transfusions, transfusions of specific neutrophil subsets, or intracellular antibiotics functioning inside neutrophils that are unable to adequately kill bacteria and as such function as \"Trojan horse.\"", "Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity\nPassage: Text: Nucleoside analogs have been historically used for anti-cancer chemotherapy because they inhibit cellular DNA/RNA polymerases . More recently, nucleoside analogs have expanded their therapeutic applications and are being used to develop antiviral drugs against a wide range of serious and life-threatening viruses. Some nucleoside analog drugs targeting specific viral polymerases , and sofosbuvir for hepatitis C virus ) have been successful in clinical trials and are currently in use for the treatment of virus-infected patients. Another class of nucleoside analog drugs such as ribavirin, more broadly-acting on various viruses, has been used in conjunction with IFN-\u03b1 . Importantly, extensive Title: Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus", "Passage: POLRMT nucleotide incorporation assay. The nucleoside triphosphates tested were AT-9010 , 2'-F-2'-C-methyl UTP and 2'-C-methyl GTP . GTP and UTP were used as positive controls. Single nucleotide incorporation and chain termination experiments were conducted and analyzed as described by Cameron et al . Title: Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus", "Passage: Since the toxicity of several nucleoside triphosphate analogs are thought to be the result of their ability to inhibit human mitochondrial RNA polymerase , thus disrupting mitochondrial RNA transcription and protein synthesis , the potential for AT-9010 to inhibit POLRMT was assessed in parallel with the active TP of SOF , and the active TP of BMS-986094 , a drug known to cause toxicity via its inhibition of POLRMT . Although the active form of all three drugs were utilized by POLRMT in vitro, and this incorporation prevented subsequent cycles of nucleotide addition , their efficiency of incorporation was poor Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: The primary mechanism to explain the antiviral effect of nucleoside analogs is based on their direct action on viral polymerization. Nucleoside analogs are transported into the cells and phosphorylated by the consecutive action of viral or cellular kinases, eventually generating nucleotide triphosphates. Mature nucleotide analogs, which are similar to physiological nucleotides, can directly incorporate into the growing viral genome during polymerization, resulting in the termination of chain reaction or the accumulation of mutations . Alternatively, nucleotide analogs can bind to the nucleotide-binding region on viral polymerases and block the entry of incoming natural nucleotides. The other mechanism is based on", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Spike glycoprotein comprised of S1 and S2 subunits. The S1 subunit contains a signal peptide, followed by an N-terminal domain and receptor-binding domain , while the S2 subunit contains conserved fusion peptide , heptad repeat 1 and 2, transmembrane domain , and cytoplasmic domain . We found that the S2 subunit of 2019-nCoV is highly conserved and shares 99% identity with those of the two bat SARS-like CoVs and human SARS-CoV . Thus the broad spectrum antiviral peptides against S2 would be an important preventive and treatment modality for testing in animal models before clinical trials . Though the S1 Title: Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization", "Passage: with the remaining extracellular spike GP1 subunit. Title: Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization\nPassage: Second, SSP is an important structural component within virions alongside the spike GP1 and transmembrane GP2 subunits. Title: Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization", "Passage: GP2 subunit. We used flow cytometry to measure the surface expression of the glycoprotein using live cells stained with a conformation-specific GP1 antibody . Mutations within the WT GPC did not alter the amount of surface GP1 expression. The GP1/2 and the GP1/2 RRAA samples failed to produce a GP1 signal above background levels. Cotransfection of wild-type SSP with both the WT GPC RR-to-AA and with the GP1/2 RR-to-AA protein restored both GP2 processing and surface expression of GP1, suggesting the dibasic motif within the LCMV glycoprotein is not the driving force for secretory pathway trafficking, but rather this function", "Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice\nPassage: demonstrated that cholera toxin subunit A1-conjugated sM2 resulted in significant enhancements to the sM2-specific IgG and mucosal IgA levels compared with sM2 alone or with controls immunized with pgsA/ L. casei or PBS. Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: demonstrated that cholera toxin subunit A1-conjugated sM2 resulted in significant enhancements to the sM2-specific IgG and mucosal IgA levels compared with sM2 alone or with controls immunized with pgsA/ L. casei or PBS. Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Abstract: To develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant Lactobacillus casei strains that express conserved matrix protein 2 with or without cholera toxin subunit A1 on the surface. The surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G and mucosal IgA. However, the conjugation of cholera toxin subunit A1 induced more potent mucosal, humoral and cell-mediated immune responses. In a challenge test with 10 MLD of A/EM/Korea/W149/06, Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: The pgsA-expressing vector was used to construct plasmids containing the highly conserved consensus sM2 gene, with or without the cholera toxin subunit A1 . Plasmids were transformed into L. casei cells. The expression levels of pgsA-sM2 and pgsA-CTA1-sM2 were monitored by immunoblotting using anti-pgsA, anti-M2 or anti-CT polyclonal antibodies .", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: disinfectant, wipe twice with 75% ethanol for non-corrosion resistance, once /4 hours. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: In addition to the above, disinfect the examination bed and ground with chlorinated disinfectant Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: disinfectant, once /4 hours. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: In addition to the above routine disinfection procedure, air disinfection is conducted for 30 min", "Title: Estimating the number of infections and the impact of non-\nPassage: In China, strict movement restrictions and other measures including case isolation and quarantine Title: Lessons from the History of Quarantine, from Plague to Influenza A", "Passage: who might have been exposed to SARS to voluntarily quarantine themselves. In China, police cordoned off buildings, organized checkpoints on roads, and even installed Web cameras in private homes. There was stronger control of persons in the lower social strata . Public health officials in some areas resorted to repressive police measures, using laws with extremely severe punishments , against those who violated quarantine. As had occurred in the past, the strategies adopted in some countries during this public health emergency contributed to the discrimination and stigmatization of persons and communities and raised protests and complaints against limitations and travel Title: Pandemic (H1N1) 2009 among Quarantined Close Contacts, Beijing, People\u2019s Republic of China", "Passage: Because of the high rates of illness and death among the initial case-patients with pandemic 2009 , the Chinese government decided to prevent and contain the rapid spread of disease through tracing and quarantine of persons who had close contact with persons with confi rmed cases of pandemic 2009. Beijing, the capital of the People's Republic of China, took strict containment and control measures through October 2009. The Beijing municipal government implemented border entry screening, ILI screening in hospitals, health follow-up of travelers from overseas, and quarantine and testing of close contacts to identify new introduction of cases and local Title: Early responses to H7N9 in southern Mainland China", "Passage: of a separation between military and public healthcare . Indeed it was not until SARS had spread to several neighbouring countries that it was publicly announced in China . Partially as a result of criticism of their handling of the SARS crisis the Chinese government was keen to rapidly release accurate information about the novel H7N9 threat. Two weeks after the first case the Emergency Office of the Ministry of Health provided a series of behavioural recommendations, including taking greater care when preparing poultry or eggs, increasing hand-washing, ventilating homes and distancing oneself from those seeming to be infected .", "Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication\nPassage: Study has shown that about 40-80% of cats are detected with FECV shedding in their faeces . About 12% of these FECV-positive cats have developed immune-mediated fatal FIP disease . The prevalence of FIP among felines is due to continual cycles of infection and reinfection of FECV and indiscernible clinical symptoms of infected cats with FECV at an early stage before the progressive development of FIPV. Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication", "Passage: Text: Feline Infectious Peritonitis Virus is an enveloped virus with a nonsegmented, positive sense, single-stranded RNA genome. FIPV is grouped as feline coronavirus , under the family Coronaviridae. FCoV is divided into two biotypes, namely, Feline Enteric Coronavirus , a ubiquitous enteric biotype of FCoV, and FIPV, a virulent biotype of FCoV . The relationship between these two biotypes still remains unclear. Two hypotheses have been proposed, internal mutation theory and circulating high virulent-low virulent theory. Internal mutation theory stated that the development of FIP is due to the exposure of cat to variants of FCoV which have been mutated Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication", "Passage: Vaccination against FIPV with an attenuated, temperature-sensitive strain of type II FIPV induces low antibody titre in kittens that have not been exposed to FCoV. However, there is considerable controversy on the safety and efficacy of this vaccine, since the vaccine contains type 2 strain, whereas type 1 viruses are more prevalent in the field . In addition, antibodies against FIPV do not protect infected cats but enhance the infection of monocytes and macrophages via a mechanism known as Antibody-Dependent Enhancement . Besides vaccines, several antiviral drugs such as ribavirin, 2 BioMed Research International interferons, and immunosuppressive drugs have been Title: Pathology in Captive Wild Felids at German Zoological Gardens", "Passage: Fourteen animals suffered from enteritis. Morphologic findings in the small intestine of 6 of these animals shared feature of feline parvovirus infection consisting of crypt dilation with accumulated cellular debris, villous atrophy, fusion and crypt regeneration. Concurrent panmyelophthisis was only present in a 3-year-old Bengal tiger . However, neither parvovirus-nor FeLV-antigen was detected immunohistologically within the intestinal tract of these animals. FIV antibodies were shown in 2 lions suffering from enteritis . Similarly, chronic enteritis is reported to occur in 19% of FIV-infected domestic cats . Although an impact of FIV infection on the development of enteritis could not be", "Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: The response by the US arguably began in March 2014 when CDC deployed personnel to investigate Ebola cases in Guinea, and further on July 9, 2014 with the activation of CDC's Emergency Operations Center. However, because EVD was largely out of the public's eye until the fall of 2014, its response was similarly delayed. That is, the peak number of EVD cases in Liberia was September 21, 2014; one week after President Obama's announcement to commit 3000 troops and provide additional aid to the Ebola response effort and one month after WHO declared it a public health emergency of international Title: European Monitoring Systems and Data for Assessing Environmental and Climate Impacts on Human Infectious Diseases", "Passage: The EC funds human surveillance systems through ECDC and research projects. Severe animal disease outbreaks are notified to the European Commission as well as to ADNS and OIE. The Commission coordinate several systems and platform to address public health threats and emergencies in the EU, including the network of the Early Warning and Response system . DG-SANCO G2 coordinates notification of outbreaks in animals. Title: CDC Summary 21 MAR 2020,\nPassage: An important part of CDC\u2019s role during a public health emergency is to develop a test for the pathogen and equip state and local public health labs with testing capacity. Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: At both facilities, we contacted the Medical Superintendents to obtain permission to attend their morning meetings to explain the aims and objectives of the work to HCWs. During this time, HCWs were given the opportunity to ask questions. Two field assistants were stationed at each of the study sites for data capture. Some of the questions asked included the organism responsible for EVD, the mode of transmission of the disease, HCW preparedness to handle any EVD case and among other things early clinical features of the infection.", "Title: Estimating the number of infections and the impact of non-\nPassage: to the infection fatality ratio. Title: Estimating the number of infections and the impact of non-\nPassage: population-averaged infection fatality ratio (adjusted for the age structure and contact patterns of Title: Estimating the number of infections and the impact of non-\nPassage: 19 infection-fatality-ratio ifr 9 together with a distribution oftimes Title: Estimating the number of infections and the impact of non-\nPassage: individuals per day given the infection fatality ratio and the infection-to-death distribution on", "Title: Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis\nPassage: have a broad range of specificities, although their affinity for any particular pathogen might be low . Either scenario requires the host to expend energy to produce antibodies that are poorly designed to neutralize or eliminate the pathogen. Since polyclonal B cell activation appears to parallel a deficiency of antigen-specific T cells, it suggests that the phenomenon reflects a kind of \"desperation\" by the host, or \"all-out-war\" in hopes that the pathogenic threat can be handled using the \"brute force\" of natural antibodies. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: While some studies have suggested that Gn glycoproteins are directed more rapidly into the ubiquitin-proteosome pathway than are apathogenic forms, others have interpreted differences in the handling of Gn glycoproteins across hantavirus species by the ubiquitin-proteosomal system as independent of pathogenicity . Some investigators have directed their efforts toward identifying a differential capacity, either kinetic or in absolute magnitude, in the ability of pathogenic and apathogenic hantaviruses to elicit an interferon response in cells. One premise that emerges is that apathogenic forms would tend to induce an earlier innate response that would render it more likely that the virus would Title: Using the Pathogenic and Nonpathogenic Nonhuman Primate Model for Studying Non-AIDS Comorbidities", "Passage: the integrity of mucosal barrier, and consequently, there is no increase in microbial translocation . Therefore, there is a general consensus that lack of disease progression in natural hosts is due to their ability to avoid the negative consequences of SIVrelated inflammatory responses. We confirmed the impact of chronic immune activation and inflammation on driving disease progression by administering Ontak to chronically SIVagm-infected AGMs. Ontak administration resulted in the increased levels of immune activation and inflammation and consequently enhanced viral replication and mucosal CD4 + T cell depletion . In other sets of experiments, we mimicked microbial translocation by administering Title: Using the Pathogenic and Nonpathogenic Nonhuman Primate Model for Studying Non-AIDS Comorbidities", "Passage: Intestinal permeability is also increased in multiple pathogenic conditions, such as inflammatory bowel disease, pancreatitis, graft-versus-host disease, excessive alcohol consumption, as well as obesity and diabetes or with age . The extensive studies of this process show that microbial products can stimulate the innate and adaptive effectors both locally and systemically. In addition to these effects on the immune system, microbial products may also stimulate nonimmune cells . In HIV-infected patients, microbial translocation has characteristic features: thus, generalized immune activation is associated with preferential loss of cell subsets involved in maintaining epithelial integrity at mucosal surfaces and antimicrobial immunity, such", "Title: In China, Students in Crowded Dormitories with a Low Ventilation Rate Have More Common Colds: Evidence for Airborne Transmission\nPassage: is that the virus is transferred through airborne spread . During the SARS epidemic, early preventive messages to the public were to wash hands and, generally to avoid ''direct'' contact spread. Later, analysis of the temporal and spatial distributions of SARS cases in a large community outbreak in Hong Kong and the correlation of these data with the three-dimensional spread of a virus-laden aerosol plume indicated an important role for airborne spread of droplet nuclei . Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Similar to other coronavirus infections, SARS-CoV is easily spread from person-to-person via respiratory droplets and secretions as well as through nosocomial contacts . In addition to transmission of SARS-CoV through natural aerosols from infected patients, it was found that in Hong Kong the SARS-CoV could also be transmitted by mechanical aerosols . Environmental factors had an important role when it was discovered that during the Amoy Gardens housing estate outbreak as many as two-thirds of infected persons had diarrhea, SARS-CoV was excreted in their stools, and that aerosols arising from the flushing of toilets could transmit the virus . Healthcare Title: In memory of Patrick Manson, founding father of tropical medicine and the discovery of vector-borne infections", "Passage: Amoy was known as just another white man's grave in the tropics which is hot and humid. The streets were narrow, irregular and filthy with excreta and litters. In those days, the only machinery for sanitation at Amoy was the pigs and dogs which ate up the excreta and litters. The inhabitants were in extreme poverty who subsisted on rice and sweet potatoes occasionally flavoured with vegetable pickles and salted fish. The area was highly endemic for malaria, typhoid fever, dengue fever and leprosy. His estimation by survey showed that about 1 in 450 inhabitants were infected by leprosy. In Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Transmission of respiratory viruses generally happens through large respiratory droplets, but some respiratory viruses can spread through fine particle aerosols , and indirect transmission via fomites can also play a role. Coronaviruses can also infect the human gastrointestinal tract , and faecal-oral transmission might also play a role in this instance. The SARS-CoV superspreading event at Amoy Gardens where more than 300 cases were infected was attributed to faecal-oral, then airborne, spread through pressure differentials between contaminated effluent pipes, bathroom floor drains and flushing toilets . The first large identifiable superspreading event during the present 2019-nCoV outbreak has apparently taken", "Title: CDC Summary 21 MAR 2020,\nPassage: For people who are ill with COVID-19, but are not sick enough to be hospitalized, please follow CDC guidance on how to reduce the risk of spreading your illness to others. People who are mildly ill with COVID-19 are able to isolate at home during their illness. Title: Hospital Triage System for Adult Patients Using an Influenza-Like Illness Scoring System during the 2009 Pandemic\u2014Mexico", "Passage: to calculate patients' ILI-scores . Clinicians used an ILI-score $16 , their judgment of patients' severity of illness and proximity to the hospital to decided whether to admit the patient and treat them with oseltamivir. Patients with intermediate ILI-scores were discharged from the ER, treated with oseltamivir and followed daily by phone for 10 days. Those with low ILI-scores were discharged without antiviral treatment, and instructed to return if their symptoms worsened. Title: Influenza pandemic intervention planning using InfluSim: pharmaceutical and non- pharmaceutical interventions", "Passage: Severe cases seek medical help on average one day after onset of symptoms, whereby the waiting time until visiting a doctor is exponentially distributed. Very sick and extremely sick patients who visit a doctor may be offered antiviral treatment. Very sick patients are advised to withdraw to their home until the disease is over whereas extremely sick cases are immediately hospitalized . Death rates of extremely sick and hospitalized cases are age-dependent. Whereas asymptomatic and moderately sick patients who have passed their duration of infectivity are considered healthy immunes, very sick and extremely sick patients first become convalescent before they Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Mild patients generally use a nasal catheter and a mask for oxygen. Adjust the oxygen flow as appropriate according to the patient's condition and doctor's instruction, and Requirements to the medical staff request 6. Medical personnel enter the isolation area with proper self-protection through designated channels.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The VEE replicon systems are particularly appealing as the VEE targets antigen-presenting cells in the lymphatic tissues, priming rapid and robust immune responses . VEE replicon systems can induce robust mucosal immune responses through intranasal or subcutaneous immunization , and subcutaneous immunization with virus-like replicon particles expressing HA-induced antigen-specific systemic IgG and fecal IgA antibodies . VRPs derived from VEE virus have been developed as candidate vaccines for cytomegalovirus . A phase I clinical trial with the CMV VRP showed the vaccine was immunogenic, inducing CMV-neutralizing antibody responses and potent T cell responses. Moreover, the vaccine was well tolerated and Title: Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice", "Passage: Venezuelan equine encephalitis virus replicon , lacks its structural protein genes and expresses green fluorescent protein under its subgenomic promoter. Transformed Escherichia coli containing the WNV and VEE replicon plasmids were grown at 37\u02daC. E. coli stocks containing the packaging vector were grown at 25\u02daC. WNV, VEE, and Semliki Forest virus replicon plasmids were linearized with Xba1, Not1, or Spe1 , respectively. RNA was in vitro transcribed using mMESSAGE mMACHINE mRNA kit according to the manufacturer's instructions. Title: Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice", "Passage: experimental procedure, allowing for more efficient optimization of other parameters, we used FlyFectin in subsequent experiments at an RNA to reagent ratio of 1 \u03bcg RNA to 4 \u03bcL FlyFectin. Transfection efficiency for these parameters was quantified using a VEE replicon RNA that expresses high levels of GFP under the subgenomic promoter. Both VEE and WNV efficiently replicate in C6/36 cells . The VEE system was used because it is more specific and sensitive than using an antibody to detect cells transfected with WNV replicon in C6/36 cells, which are highly autofluorescent. The percentage of GFP-positive cells was determined by Title: Viral vector-based influenza vaccines", "Passage: VEE is an appealing vaccine vector, as it was previously shown that VEE mainly targets antigen-presenting cells in the lymphoid tissues and therefore primes rapid and robust immune responses. 103 SIN, SFV and VEE have all been tested as influenza vaccine vectors . An SFV vaccine expressing the HA and NP genes could protect mice from infection with A virus; 99 the same held true for a SIN replicon expressing either the HA gene or an immunodominant CD8 C T-cell NP epitope. 104, 105 VEE was more extensively evaluated as an influenza vaccine vector, VEE-H1 vaccination protected mice from infection", "Title: Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting\nPassage: Determining the transmission likelihood. We assume cases were classified correctly from case investigation as imported or locally-acquired based on recent travel history. Following this assumption, locally acquired cases could have both infected others and been infected themselves. However imported cases could only infect others, as we assume their infection was acquired outside of the country. There were no confirmed relapse cases in the dataset, and all cases were treated with primaquine and chloroquine after being detected. Treatment is initiated before cases are confirmed by microscopy . Active case detection is initiated locally following a confirmed case and in active foci Title: Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico", "Passage: There was no significant difference between cases and population controls, regardless of age. When comparing cases versus intradomestic controls, we observed a statistically significant difference in time spent in area out of the municipality but in the State . Title: Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting", "Passage: Supplementary Note 2: Sensitivity analysis 71 We explored the sensitivity of our approach by varying the threshold likelihood for linking cases, , 72 and the threshold gain in marginal likelihood used to define the number of edges to create, K. We We assume cases were classified correctly from case investigation as imported or locally-acquired 85 based on recent travel history. Following this assumption, locally acquired cases could have both 86 infected others and been infected themselves. Imported cases could only infect others, as we assume 87 their infection was acquired outside of the country. We also assume a case showing Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,", "Passage: The model requires data on imported-and-reported cases of SARS-CoV-2 infection, daily air travel volume, and surveillance capacity. We obtained data on imported-and-reported cases aggregated by destination from the World Health Organization technical report issued February 4, 2020 . We assumed a case count of 0 for locations not listed. We used February 4 as the cutoff for cumulative imported-and-reported case counts because exported cases from Hubei Province dropped rapidly after this date , likely because of travel restrictions for the province implement on January 23. We defined imported-and-reported cases as those with known travel history from China; of those, 83%", "Title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression\nPassage: Time-of-addition experiments revealed that maximal effects were achieved when glycyrrhizin was continuously present starting with a 1 h pre-incubation period . Addition of glycyrrhizin post infection showed reduced antiviral effects while pre-incubation alone or glycyrrhizin addition during the adsorption period did not significantly affect H5N1 replication. Title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression", "Passage: antiviral plus immunomodulator treatment reduced H5N1-induced mortality in mice . Therefore, antiinflammatory and immunomodulatory effects exerted by glycyrrhizin may be beneficial for treatment of H5N1. Also, glycyrrhizin is a known antioxidant and antioxidants were already shown to interfere with influenza A virus replication and virus-induced pro-inflammatory responses . Title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression", "Passage: Experimental results suggested that glycyrrhizin might be able to affect seasonal influenza A virus disease by antiviral and immunomodulatory effects . Mice were prevented from lethal H2N2 infection by glycyrrhizin although no influence on virus replication was detected. The mechanism was suggested to be induction of interferon-c in T-cells by glycyrrhizin . Moreover, glycyrrhizin was shown to influence seasonal influenza A virus replication through interaction with the cell membrane . However, these effects were observed only in concentrations $200 mg/ml when glycyrrhizin was added during the virus adsorption period. Since glycyrrhizin addition during the adsorption period did not influence H5N1 Title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression", "Passage: as constituents of anti-influenza treatment strategies that may save lives in an influenza pandemic situation . Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1-caused disease.", "Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China\nPassage: The employed recombination detection methods revealed that SAIBK is a chimera virus, with recombination by the SC021202 strain as a major parent and the H120 vaccine strain as a minor parent. The first and second recombination regions were located at positions 7231 to 9126 and 13437 to 14473 in genes 1a and 1b, respectively. There were two other recombination regions detected at positions 951 to 1067 and 5393 to 5605 of SAIBK, which were recombined with the SC021202 strain as a major parent and the H52 vaccine strain as a minor parent. The recombination detection results suggested that SAIBK is Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China", "Passage: The complete genome of the SAIBK strain is 27,534 nucleotides in length, including the poly tail. It has a classical IBV genome organization with 10 open reading frames : Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China\nPassage: Phylogenetic analysis of the complete genome results indicated that the SAIBK strain clusters into the same branch as the IBV YN strain and the SC021202 strain . The S1 subunit of the IBV genome is the major determinant of serotype , and S1 analysis indicated that the SAIBK strain has a 4/91-like serotype. Title: GI-type T4SS-mediated horizontal transfer of the 89K pathogenicity island in epidemic Streptococcus suis serotype 2", "Passage: As the name implies, 89K is approximately 89 kb in length, flanked by a perfect 15 bp direct repeat, and contains a putative phage-related integrase gene at its 3\u2032 end. These architectural features strongly suggest that it may have been acquired by horizontal gene transfer . Meanwhile, the internal modular organization of 89K indicates that it was generated by multiple recombination events because it carries several unrelated gene blocks found in widely divergent species, making it difficult to ascertain its initial origin. A better understanding of the molecular biology of 89K will undoubtedly provide important insight into the emergence, virulence,", "Title: Microbial Proteases Applications\nPassage: conditions. This involvement of proteases may lead them to produce a therapeutic agent against deadly diseases, such as cancer and AIDS . Proteases similar in sequences and structures are grouped into clans and families, which are available in the MEROPS database . The proposed review highlights the proteolysis, function, and wide range of sources among different bacteria of microbial proteases. It also discusses the broad range of applications and upcoming advancement for the discovery of new and fresh proteases, especially alkaline proteases from bacteria . Title: Microbial Proteases Applications", "Passage: Proteases have been successfully produced by researchers from different microbial sources. Microbes account a two-thirds share of commercial protease around the globe . Since the advent of enzymology, microbial proteolytic proteases have been the most widely studied enzyme. These enzymes have gained interest not only due to their vital role in metabolic activities but also due to their immense utilization in industries . The proteases available in the market are of microbial origin because of their high yield, less time consumption, less space requirement, lofty genetic manipulation, and cost-effectiveness, which have made them suitable for biotechnological application in the market Title: Microbial Proteases Applications", "Passage: of existing life on earth, such as animals, plants, and microbes. By a process of fermentation, proteases can be isolated and purified in a relatively shorter period of time, exhibiting high substrate specificity and catalytic activity . It is estimated that proteases account for 1-5% of the genome of infectious organisms and 2% of the human genome . According to researchers, proteases control the activation, synthesis, and turnover of proteins to regulate physiological processes . Different physiological processes, such as formation, birth, aging, and even death are regulated by proteases . Proteases are involved in normal and pathophysiological processes or Title: Early Days of Food and Environmental Virology", "Passage: reported , but these are not necessarily agents of human infection, nor are they necessarily infectious as detected. We were able to show that some proteases and some microbes would attack enteroviruses ; CA9 was especially susceptible to enzyme attack . By differential radionuclide labeling, we demonstrated that CA9 and PO1 in lake water were inactivated by Pseudomonas aeruginosa, which selectively used their coat protein, but not the RNA, as substrate .", "Title: Innovations in research ethics governance in humanitarian settings\nPassage: 6) Ensure that potential participants are free to refuse or withdraw from the research at any stage without penalty.. authority or partner is encouraged. If relevant and possible, consultation with a body representing the community is desirable. 7. If the decision for exemption from review is taken by the medical directors, the MSF responsibility to ensure that ethical requirements are met is similar to reviewed projects. This exemption, in addition, does not exempt MSF from compliance with regulatory requirements in the country from where the data originate. National or institutional ethical review may still be required. Title: Responding to the COVID-19 pandemic in complex humanitarian crises", "Passage: The Sphere Handbook, a collection of rights-based guidelines for humanitarian response, is the foremost authority on minimum standards for humanitarian assistance . However, despite the indisputable evidence for the efficacy of hand hygiene for reducing both bacterial and viral pathogen transmission, humanitarian WASH standards are based on evidence pertaining to the prevention of illnesses transmitted by the faecal-oral route, with the focus on hand hygiene proximate to latrines . And yet, latrines in crisis settings are often shared and distant from residential shelters, conferring a high risk of gender-based violence . Gender-based violence around latrines is an important deterrent for Title: Innovations in research ethics governance in humanitarian settings\nPassage: or other difficult circumstances, where there is great vulnerability and pressing humanitarian needs. Title: Innovations in research ethics governance in humanitarian settings", "Passage: First, the impact of any new framework should be continuously assessed. While, in this case, we can already sense after six months implementation, that it has been adopted very easily and seems to be much more \"intuitive\" than the previous framework, a more rigorous evaluation of its acceptance, implementation and impact on the quality of research protocols would be useful not only for MSF, but also for other organisations that are facing the same challenges and might wish to adopt and/or adapt it.", "Title: Multiplexed Nucleic Acid Programmable Protein Arrays\nPassage: These results indicate that M-NAPPA can be used for preliminary high throughput screening of novel protein-protein interactions. The screen can then be followed by a verification step using deconvoluted spots via NAPPA to identify the specific proteins that are involved. Title: Multiplexed Nucleic Acid Programmable Protein Arrays\nPassage: Third, we showed that M-NAPPA can be used in protein-protein interaction and serological screening studies. The results from M-NAPPA agreed strongly with those observed with non-multiplexed NAPPA . These data indicate that M-NAPPA presents a labor-and cost-effective strategy to initially screen for hits. Title: Evaluation of Targeted Next-Generation Sequencing for Detection of Bovine Pathogens in Clinical Samples", "Passage: the enteric and respiratory syndromes, for cases of E. coli infection, the PPA was 70% and the NPA was 100%, and for C. perfringens, the PPA was 56% and the NPA was 100%. For respiratory cases, the PPA for Mannheimia haemolytica was 78% and the NPA was 67%, and for Pasteurella multocida, the PPA was 71% and the NPA was 63%. The PPA for Histophilus somni was 100% and the NPA was 70%, and the PPA and NPA for Mycoplasma bovis were both 100%. Title: Multiplexed Nucleic Acid Programmable Protein Arrays", "Passage: To test whether M-NAPPA can be used to detect proteomic serological response, we screened ten serum samples from patients with type 1 diabetes that had been previously characterized using NAPPA arrays . A dozen hits were observed with M-NAPPA and NAPPA . Forty-nine of the 53 antigens identified by NAPPA were also detected by M-NAPPA. Four antigens, however, were detected with only one platform . These uncommon discrepancies may be due to variations in surface chemistry, plasmid concentration, printing or array processing.", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: There are elements with zero genes that fulfill many criteria for early life: ribozymes, catalytic RNAs closely related to viroids. They were recovered in vitro from 10 15 molecules , 220 nucleotides in length, by 10 rounds of selection. Among the many RNA species present in this collection of quasispecies RNAs were catalytically active members, enzymatically active ribozymes. The sequence space for 220-mer RNAs is about 3 \u00d7 10 132 . Title: Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype", "Passage: further evidence for the quasispecies behavior of RNA viruses under certain conditions. It is important to note, however, that the group selection observed in this study resulted from relatively large population size in passages that reached high MOI by the time cell monolayers were lysed for subsequent passage. It is possible that in conditions where MOI is low, or when population bottlenecks occur , that the emergence of such minority variants would be delayed or impeded. Title: Differential Shape of Geminivirus Mutant Spectra Across Cultivated and Wild Hosts With Invariant Viral Consensus Sequences", "Passage: Animal and plant RNA viruses exist as viral quasispecies that adapt to changing environments by evolving rapidly . Viral quasispecies are defined as distributions of nonidentical but related genomes subjected to a continuous process of genetic variation, competition, selection and genetic drift, and which act as a unit of selection . Their high genetic diversity in host populations is partially explained by the low replication fidelity of viral RNA-dependent DNA or RNA polymerases , which lack proofreading activity . Eukaryotic single-stranded DNA viruses do not encode DNA polymerases and replicate their genomes using unknown host cell polymerases. High mutation frequencies Title: Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype\nPassage: variants to the overall fitness of the entire population. Our results underscore the importance of characterizing RNA virus quasispecies during adaptation and virus evolution.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: The filamentous phage particle is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups . The regularity of the phage pVIII lattice and its diversity of chemically addressable groups make it an ideal scaffold for bioconjugation . The most commonly used approach is functionalization of amine groups with NHS esters , although this can result in unwanted acylation of pIII and any displayed biomolecules. Carboxyl Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: The filamentous phage particle is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups . The regularity of the phage pVIII lattice and its diversity of chemically addressable groups make it an ideal scaffold for bioconjugation . The most commonly used approach is functionalization of amine groups with NHS esters , although this can result in unwanted acylation of pIII and any displayed biomolecules. Carboxyl Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: the phage filament Hess et al., 2012) , this pioneering FIGURE 3 | Chemically addressable groups of the filamentous bacteriophage major coat protein lattice. The filamentous phage virion is made up of \u223c2,500-4,000 overlapping copies of the 50-residue major coat protein, pVIII, arranged in a shingle-type lattice. Each monomer has an array of chemically addressable groups available for bioorthogonal conjugation, including two primary amine groups , three carboxyl groups and two hydroxyl groups . The 12 N-terminal residues generally exposed to the immune system for antibody binding are in bold underline. Figure adapted from structural data of Marvin, 1990 , Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: the phage filament Hess et al., 2012) , this pioneering FIGURE 3 | Chemically addressable groups of the filamentous bacteriophage major coat protein lattice. The filamentous phage virion is made up of \u223c2,500-4,000 overlapping copies of the 50-residue major coat protein, pVIII, arranged in a shingle-type lattice. Each monomer has an array of chemically addressable groups available for bioorthogonal conjugation, including two primary amine groups , three carboxyl groups and two hydroxyl groups . The 12 N-terminal residues generally exposed to the immune system for antibody binding are in bold underline. Figure adapted from structural data of Marvin, 1990 ,", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: stations, long-distance bus stations and passenger terminals. As of January 17, a total of nearly 0.3 million people had been tested for body temperature . In Wuhan, there are about 2.87 million mobile population . We assumed that there was 0.1 million people moving out to Wuhan City per day since January 10, 2020, and we believe that this number would increase until 24 January, 2020. This means that the 2.87 million would move out from Wuhan City in about 14 days. Therefore, we set the moving volume of 0.2 million per day in our model. Since the population of Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: Wuhan was about 11 million at the end of 2018 , the rate of people traveling out from Wuhan City would be 0.018 per day. However, we assumed that the normal population mobility before January 1 was 0.1 times as that after January 10. Therefore, we set the rate of people moving into and moving out from Wuhan City as 0.0018 per day . Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020\nPassage: cases as of 17 January 2020 . The former study from the United States assumes that the catchment area population is 10 million . Title: Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey", "Passage: This study was performed in seven urban regions and two rural areas of China with over one million people in each region. Regarding the urban sites, Beijing as the capital of China locates in the northeast; Shanghai is a municipality in the east of China; Wuhan and Zhengzhou are both in the centre of China; Xi'an in the northwest of China is the provincial capital of Shanxi province; and Shenzhen of the Guangdong province is in the southeast of China. As for the rural sites, Jingzhou county and Zhengzhou county, from Hubei and Henan provinces, respectively, both locate in the", "Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: Any statement that is factually inaccurate but stated as question of hearsay \"Some are asking if Ebola is spread through the air\" Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: what to do, or question the veracity of the advice offered, they are more likely to respond by denying the risk or transferring it to others . Whilst most of the participants in the general population groups regarded swine flu as \"bit of a joke, really\" others reported feelings of anxiety, fear or panic. In particular, reports of flu-related deaths gave rise to more serious concern. Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research", "Passage: Some participants questioned the extent to which the H1N1 virus really represented a pandemic or a \"true emergency\", referring to the fact that their own personal experiences did not confirm this impression with regard to either severity or spread . Most participants regarded the disease as relatively mild and as similar to other types of influenza , felt that the danger or risk was exaggerated, and did not take the government's urgent messages seriously . However, others saw the disease as more severe or potentially serious and sometimes deadly , and referred to the relatively high risk to young people Title: Avian influenza outbreak in Turkey through health personnel's views: a qualitative study", "Passage: things. She slept with the doll for many nights. Why didn't anyone underline this occasion? Why was the people's psychological status not taken into account? Why wasn't attention paid to the problems related to the housing infrastructure or the lack of clean water? I still can't accept this; it still affects me.\"", "Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies\nPassage: involving 82 patients in South Korea, and the median incubation period was estimated to be 7 days with a range of 2 to 17 days . At the end of 2015, there were 1621 confirmed MERS with a 36% mortality rate . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Although DCs appear to suffer the equivalent of a 'common cold' from MERS-CoV infection, in humans, the virus can be a more serious and opportunistic pathogen associated with the death of up to 40 % of reported cases. It has yet to be established whether infections thought to have been acquired from an animal source produce a more severe outcome than those spread between humans . Studies have established that the mean incubation period for MERS is five to six days, ranging from two to 16 days, with 13 to 14 days between when illness begins in one person and Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: families and healthcare settings . Clinical pictures of this infection varied from asymptomatic to mild respiratory symptoms to severe respiratory distress and death . Severe ailment can often cause respiratory catastrophes that need mechanical ventilation and support in ICUs across different healthcare settings . Studies have suggested an incubation period of 16 days with a mean of 5-6 days , while the median time until death is 11-13 days among severely ill patients . e gold standard test for the detection of this virus is real-time reverse-transcription polymerase chain reaction assays . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: subsequently spreads to another . Among those with progressive illness, the median time to death is 11 to 13 days, ranging from five to 27 days . Fever and gastrointestinal symptoms may form a prodrome, after which symptoms decline, only to be followed by a more severe systemic and respiratory syndrome .", "Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case\nPassage: The histopathologic features in different organs are shown in Fig. 2 . Lung showed diffused alveolar damages including intraalveolar edema, focal intra-alveolar hemorrhage, necrosis of alveolar line cells, focal desquamation of pneumocytes in alveolar spaces, interstitial mononuclear inflammatory cell infiltrates, and extensive hyaline membranes. Trachea showed focal denudation of the epithelium with edema, and mononuclear inflammatory cell infiltrates. Spleen showed depletion of lymphocytes with congestion and organized infarcts. Axillary lymph-node was congested with depletion of lymphocytes. The central nervous system showed extensive edema with focal neuronal necrosis in hippocampus. Diastem between Purkinje cells layer and particle cells layer showed focal Title: Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung", "Passage: All patients underwent high-resolution CT of the chest upon initial evaluation. A radiologist who specializes in diffuse parenchymal lung disease reviewed the CT scans. The extent and prevalence of abnormalities were measured in the areas as follows: from the lung apex to the carina, from the carina to the upper pulmonary vein, and from the upper pulmonary vein to the base of the lung. HRCT images were assessed to determine the extent of parenchymal abnormalities, including ground-glass opacity , reticulation, honeycombing, consolidation, and emphysema. The extent of these abnormalities was determined using a 10 % scale for six zones . Title: Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis", "Passage: Four-micrometer-thick sections were cut from the lung tissue blocks and stained with H&E for the histopathological examinations in addition to Periodic acid-Schiff stain, Grocott's methenamine silver stain and Gram stain to identify any infectious pathogens in the presence of bronchopneumonia. Bronchopneumonia was conclusively diagnosed based on histopathological evidence, such as neutrophil infiltration, fibrinopurulent exudate accumulation or abscess formation in the broncho-bronchioloalveolar space. For immunohistochemical detection of cytomegalovirus antigens, the sections were incubated with a mouse monoclonal anti-CMV antibody for 30 minutes. Secondary antibody peroxidase-linked polymers were then applied, and the sections were incubated with a solution consisting of 20 mg Title: Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine\u2010origin influenza type A/H1N1 and acute respiratory failure", "Passage: 10% formalin-fixed, routinely processed, paraffin-embedded blocks, were stained with hematoxylin-eosin. The following methods of histochemical staining were carried out: Grocott's methenamine silver stain, Brown-Brenn, and Ziehl-Neelsen. The following pathological changes were analyzed: a) necrotizing bronchiolitis, b) alveolar collapse, c) dilatation of the airspaces, d) hyaline membrane, e) fibroplasia, f) squamous metaplasia, g) multinucleated cells, h) alveolar hemorrhage, i) acute inflammatory exudates, j) atypical pneumocytes. Pathological changes were graded, using two sections, according to a five-point semiquantitative severity-based scoring system as: 0 = normal lung parenchyma, 1 = changes in 1-25%, 2 = changes in 26-50%, 3 = changes in 51-75%,", "Title: Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery\nPassage: Role of NA in virus movement. Generally, influenza virus NA is thought to mediate progeny virus budding from host cells 25 . Nevertheless, NA inhibitors reportedly suppress virus infection, indicating a major role of NA in infection . However, the specifics of this functional role remained unclear. We hypothesised that NA contributes to the movement of virus particles toward endocytosis regions. To test this hypothesis, we examined the effect of a NA inhibitor, zanamivir, on Aichi2 virus crawling and gliding motions on fetuin-coated surfaces. This NA inhibitor completely blocked virus crawling and gliding, resulting in the immobilisation of virus particles Title: Characteristics of human infection with avian influenza viruses and development of new antiviral agents", "Passage: Viral neuraminidase enables progeny virus to be cleaved from its receptor and spread to other cells. The neuraminidase inhibitors, which are cyclopentane or pyrrolidine derivatives, can prevent the further spread of influenza by blocking the release of newly formed particles . Four commercial neuraminidase inhibitors have been approved for use in humans . The first two are widely used in most countries and are effective against influenza infection. Particularly for oseltamivir, early administration can not only shorten the duration of ill- Table 2 . Main Characteristics of current available antivirals . npg ness but also facilitate symptom resolution . Neuraminidase Title: Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release", "Passage: a deletion of two amino acids in the stalk region , but also contained similar glycosylation sites with other N2s 12 . NMR spectroscopy was used to assess NA activity of the wild type G1 virus , a reverse genetics virus where the two amino acid deletions were restored and a reverse genetics virus with a mutation in P431K which this substitution could change the orientation of the NA 430 loop and influence Sia binding 24 . The main role of viral NA is to cleave Sia from the epithelial surface as well as facilitate viral penetration through the sialylated Title: Progress of small molecular inhibitors in the development of anti-influenza virus agents", "Passage: NA is a viral enzyme that is made up of four identical subunits and is anchored to the membrane of the virus . NA plays a key role in the spreading of the virus. The terminal neuraminic acid residues of the glycoproteins of the newly formed virion progeny form glycosidic linkages with the neuraminic acid receptor on the host-cell surface; this glycosidic linkage is cleaved by NA, which thereby assists in the release of the virion progeny from the infected cells . Therefore NA is an attractive target for anti-influenza research, and inhibitors of NA containing a Neu core have", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Text: The prevalence of chronic airway inflammatory disease is increasing worldwide especially in developed nations . This disease is characterized by airway inflammation leading to complications such as coughing, wheezing and shortness of breath. The disease can manifest in both the upper airway and lower airway which greatly affect the patients' quality of life . Treatment and management vary greatly in efficacy due to the complexity and heterogeneity of the disease. This is further complicated by the effect of episodic exacerbations of the disease, defined as worsening of disease symptoms including wheeze, cough, breathlessness and chest tightness . Such exacerbations Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The possibility that bats were an animal host of MERS-CoV was initially widely discussed because of the existing diversity of coronaviruses known to reside among them . Conclusive evidence supporting bats as a source for human infections by MERS-CoV has yet to be found, but bats do appear to host ancestral representatives . However, these are not variants of the same virus nor always within the same phylogenetic lineage as MERS-CoV; they are each a genetically distinct virus. Bat-to-human infection by MERS-CoV is a purely speculative event. The only piece of MERS-CoV-specific evidence pointing to bats originates from amplification of Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Since that first report, a slow discovery process over the following two to three years revealed a virus that had infected over 90 % of adult dromedary camels in the KSA , also DCs across the Arabian Peninsula and parts of Africa that are a source of DC imports for the KSA . To date, MERS-CoV has not been detected in DCs tested in zoos or herds from other parts of the world . Occasionally, virus is transmitted from infected DCs to exposed humans. Subsequent transmission to other humans requires relatively close and prolonged exposure . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: of a virus that initially and predominantly causes respiratory disease . Camels are known to produce high levels of MERS-CoV RNA in their URT and lungs . Providing support for a droplet transmission route and perhaps indicating the presence of RNA in smaller, drier droplet nuclei, MERS-CoV RNA was identified in a high volume air sample collected from a barn housing an infected DC . The precise source from which humans acquire MERS-CoV remains poorly studied but it seems likely that animal and human behavioural factors may play roles . These factors may prove important for human cases who do", "Title: Estimating the number of infections and the impact of non-\nPassage: study have implemented all major non-pharmaceutical interventions. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: through intensive counselling, and demonstration of proper wearing of masks or hand washing. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: countries, and might have modest effectiveness against the pandemic strain, because of the emergence of antiviral resistance or other reasons . Furthermore, few of these pharmaceutical measures can be applied at pandemic scale. Only non-pharmaceutical interventions including use of face masks, improved hand hygiene, cough etiquette, social distancing measures, and travel restrictions would be available to the majority of the world's population. Interpandemic influenza is associated with thousands of deaths every year in Hong Kong and likely hundreds of thousands worldwide every year , therefore simple personal protective measures could be beneficial during annual epidemics if found to be effective Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: The face masks and hand washing interventions will include an intensive counselling session to describe and demonstrate proper use of the respective hygiene aids.", "Title: CDC Summary 21 MAR 2020,\nPassage: On March 16, the White House announced a program called \u201c15 Days to Slow the Spread,\u201dpdf iconexternal icon which is a nationwide effort to slow the spread of COVID-19 through the implementation of social distancing at all levels of society. Title: CDC Summary 21 MAR 2020,\nPassage: most important response strategy to try to delay the spread of the virus and reduce the impact of disease. Title: Quantifying social distancing arising from pandemic influenza\nPassage: Things changed on the weekend of 22-23 March, when 20 people died of influenza; infection control measures were reimposed around the end of March. We assume that, from 25 March, the perceived severity of the disease was high enough to reduce transmission. These measures were continued throughout the first wave . Title: Quantifying social distancing arising from pandemic influenza", "Passage: A second wave began shortly after the infection control measures were lifted , and was clearly apparent by mid-June. Even though infection control measures were not reimposed, we assume that the high incidence was a sufficient threat to alter people's behaviour. We define this period of altered behaviour as running from mid-June to 12 August.", "Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: to define two major genotypes or groups, A and B, which are further classified into four subgroups . HMPV A2, the most frequently observed subgroup, is further divided into two proposed sub-lineages . Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: used to define two major genotypes or groups, A and B, which are further classified into four subgroups . HMPV A2, the most frequently observed subgroup, is further divided into two proposed sub-lineages . Title: Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis", "Passage: Genotyping of hMPV was performed in 27 cases, being ten cases of hMPV group A and 17 of hMPV group B . The viral strains belonged to sublineages A2 , B1 and B2 . Group A strains predominated until 2011 , while later, the most frequent was genotype B . After excluding seven patients with bacterial coinfection, there were not significant differences in the genotype of hMPV between six patients who developed ARDS and 15 who did not . Title: Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis\nPassage: Based on genetic and antigenic variability, hMPV strains have been classified in two groups or lineages and four sublineages . The virus has been reported as a common respiratory pathogen in childhood, associated mainly with upper but also with lower respiratory tract infections . During the annual epidemics, hMPV has been associated with a significant number of hospital admissions in young children .", "Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1\nPassage: on endothelial cells compromises BBB integrity and enhances monocytes adhesion and transmigration across the BBB . It is thus possible that reduced expression of DC-SIGNR, particularly the membranebound isoforms, on placental capillary endothelial cells might favour HIV-1 binding to CCR5 receptor, instead of DC-SIGNR receptor, facilitating the migration of maternal HIV-1-infected cells across the placental barrier resulting in IU transmission of HIV-1. Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1\nPassage: DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission. Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: it is not surprising that mutations increasing the affinity of DC-SIGN for pathogens have appeared that can compensate for mutations that reduce its expression. Interestingly, HIV-1 itself can also affect DC-SIGN expression. Indeed, HIV-or antibody-stimulated DC-SIGN signalling in monocytes-derived dendritic cells reduced DC-SIGN expression and prevented cell maturation . In infants harbouring the WT sequence, levels of DC-SIGN expression were significantly lower in infants born from HIV-1-positive mothers than those born from HIV-1-negative mothers . However, the impact of HIV-1 was negligible or not noticeable in infants carrying the promoter variants since baseline DC-SIGN expression levels were already low in Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: In vitro studies have shown that the interaction between DC-SIGN and HIV-1 can enhance short-term viral transfer to other susceptible cell types such as T lymphocytes . Based on these findings, a Trojan horse model has been proposed whereby was compared in CD163+ and CD1632 subsets from infants bearing or not promoter variants and born from HIV-1-negative mothers or from HIV-1-positive mothers . Results in C and D are mean 6 S.E.M. values of MFI and difference between subsets or variants was calculated with Student's t test. doi:10.1371/journal.pone.0040706.g002 HIV-1 may subvert DC-SIGN-expressing submucosal dendritic cells to promote dissemination from the", "Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019\nPassage: care workers. A considerable proportion of participants reported symptoms of depression ), anxiety ), insomnia ), and distress ). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers Patient Health Questionnaire scores among physicians vs nurses: 4.0 vs 5.0 ; P = .007; median Generalized Anxiety Disorder scale scores among men vs women: 2.0 vs 4.0 ; P < .001; median Insomnia Severity Index scores among frontline vs second-line workers: 6.0 vs 4.0 ; P < .001; median Impact of Event Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019", "Passage: and distress was assessed by the Chinese versions of the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, the 7-item Insomnia Severity Index, and the 22-item Impact of Event Scale\u2013Revised, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. RESULTS: A total of 1257 of 1830 contacted individuals completed the survey, with a participation rate of 68.7%. A total of 813 were aged 26 to 40 years, and 964 were women. Of all participants, 764 were nurses, and 493 were physicians; 760 worked in hospitals in Wuhan, and 522 were frontline health Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019", "Passage: this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19. Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019", "Passage: Abstract: IMPORTANCE: Health care workers exposed to coronavirus disease 2019 could be psychologically stressed. OBJECTIVE: To assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China. DESIGN, SETTINGS, AND PARTICIPANTS: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from 1257 health care workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 were eligible. MAIN OUTCOMES AND MEASURES: The degree of symptoms of depression, anxiety, insomnia,", "Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections\nPassage: immunocompromised patients and people with underlying comorbidities . The overall CFR of MERS is approximately 34.4% . Most fatalities have been associated with pre-existing medical conditions like chronic lung disease, diabetes, and renal failure, as well as weakened immune systems , making such individuals high risk. As a result of the immunological changes that occur during pregnancy, women who are pregnant are included in this high-risk group. Pregnant women may develop severe disease and fatal maternal and/or fetal outcomes as a result of MERS-CoV infection; however, little is known of the pathophysiology of this infection during pregnancy. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: Host resilience to emerging coronaviruses\nPassage: MERS-CoV patients had increased morbidity and mortality if they were obese, immunocompromised, diabetic or had cardiac disease .", "Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: Other bacteria that were developed as DNA vaccine carriers include Listeria monocytogenes , Shigella spp. , and Yersinia enterolica . Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Briefly, as a DNA vaccine carrier, bacteria are divided into two major groups: non-pathogenic bacteria and attenuated pathogen bacteria. The attenuated bacteria that have been studied as the DNA vaccine carrier include Salmonella spp. , Yersinia enterocolitica , Shigella spp. , and Listeria monocytogenes . Pathogen bacteria target the mucous membranes as their infection route and as a result, they are suitable for mucosal administration. However, the main disadvantage includes the likelihood of causing infection, particularly in infants and immunocompromised patients . Therefore, non-pathogen bacteria such as lactic acid bacteria may be preferable for development as DNA vaccine carriers. A Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Briefly, as a DNA vaccine carrier, bacteria are divided into two major groups: non-pathogenic bacteria and attenuated pathogen bacteria. The attenuated bacteria that have been studied as the DNA vaccine carrier include Salmonella spp. , Yersinia enterocolitica , Shigella spp. , and Listeria monocytogenes . Pathogen bacteria target the mucous membranes as their infection route and as a result, they are suitable for mucosal administration. However, the main disadvantage includes the likelihood of causing infection, particularly in infants and immunocompromised patients . Therefore, non-pathogen bacteria such as lactic acid bacteria may be preferable for development as DNA vaccine carriers. A Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: DNA vaccines are facing challenges in terms of an effective delivery system that effectively targets the immune system. As live vectors, bacteria are new promising agents for vaccine delivery. Bacteria have unique natural characteristics that promote immune responses. However, the main concern about bacteria as vaccine carrier is patient safety. Although some attenuated recombinant strains have been developed, non-pathogenic bacteria such as LAB are considered more suitable DNA vaccine carriers.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: In the current study, we propose an improved ANFIS model based on a modified flower pollination algorithm using the salp swarm algorithm . The FPA is an optimization algorithm proposed by Yang , which was inspired by the flow pollination process of the flowering plants. The FPA was employed in various optimization applications, for example to estimate solar PV parameter , solving sudoku puzzles , feature selection , antenna design , and other applications . Moreover, SSA is also an optimization algorithm proposed by Mirjalili et al. inspired by the behavior of salp chains. In recent years, the SSA was Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: An improved ANFIS model is proposed using a modified FPA algorithm, using SSA. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: On the other hand, the updating phase of the followers' positions in the SSA algorithm is applied to improve the global pollination phase in the FPA algorithm. In this improvement, there is a random variable used to switch between both phases. If r > 0.5, then the operators of the SSA is used; otherwise, the operators of the FPA are used. In general, The FPASSA starts by constructing the population ; afterward, the objective function is calculated for each solution. The solution with the lowest error value is saved to the next iteration. This sequence is repeated until meeting the Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: The proposed method called FPASSA is a hybrid of FPA and SSA, in which the SSA is applied as a local search method for FPA. The proposed FPASSA starts by receiving the historical COVID-19 dataset. Then a set of solutions is generated where each of them represents the value for the parameters of the ANFIS model. Then the quality of each solution is calculated using the fitness value, and the solution that has the best fitness value is chosen to represent the best solution. Then the probability of each solution is computed. Then the current solution will be updated, either", "Title: SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells\nPassage: Despite extensive testing of candidate MVA vaccines in humans, the basis for the hostrestriction of MVA, which is important to fully understand its attenuation, remains unknown. The large number of deletions, truncations and mutations that occurred during the long passage history of MVA in CEF severely complicates efforts to determine those changes important for its host-range defect. Indeed, a comparison of MVA with its parent CVA revealed 71 orthologous ORFs predicted to encode identical gene products, whereas the remaining 124 ORFs encode gene products with amino acid changes, insertions or deletions . One attempt to investigate the genetic changes responsible Title: SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells", "Passage: Homologous recombination was carried out by infecting CEF with 1 PFU/cell of virus, followed by transfection with assembled PCR products using Lipofectamine 2000 . After 24 h, cells were harvested and lysed by three freeze-thaw cycles. The lysates were diluted 10-fold and used to infect CEF monolayers. Fluorescent recombinant plaques were distinguished from the parental plaques and clonally purified five times. The purities of the recombinant viruses were confirmed by PCR amplification and sequencing of the modified region. MVA and recombinant viruses were propagated in CEF. Title: SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells", "Passage: at MOI of 0.001 and 0.01 . In HeLa and A549 cells, MVA-SPI-1 also exhibited an increase in staining relative to MVA, but the effect was less than in BS-C-1 and MRC-5 cells and was best discerned at a MOI of 0.1 . Title: SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells", "Passage: chicken embryo fibroblasts for the purpose of producing a safe smallpox vaccine . Initial analysis of the MVA genome revealed six major deletions compared to the parent virus . These large deletions as well as numerous additional genetic changes were confirmed by genome sequencing . Notwithstanding the loss of considerable genetic material and the consequent inability to efficiently produce infectious virus in most mammalian cells , MVA retains the ability to express viral as well as recombinant proteins regulated by VACV promoters in non-permissive cells at levels comparable to replicating VACV and to induce both humoral and cellular immune responses", "Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China\nPassage: About 971 of the 2025 cases were positive for at least one viral pathogen. Among them, IAV, RSV, HRV and PIVs were detected in 348 , 296 , 209 and 169 cases, respectively. Single infection was observed in 669 cases, and multiple infection was found in 302 . Our results also showed that RSV, IAV and HRV were the main pathogens in single viral infection cases . The monthly positive rates varied from 32\u00c15% to 75\u00c10% with a mean of 45\u00c11% . In the year 2009, when influenza A was pandemic worldwide, the positive rate started to increase in March Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: 25\u00c14 to 47\u00c19%. 40 The relatively lower co-infection rates ranging from 0\u00c124 to 26\u00c19% were reported in the studies conducted in various cities of China. 22, In most of these studies, immunofluorescence kits were used to test a lower number of respiratory viruses. It was worth to note that in the study by Peng et al. 32 in Wuhan, China, 69\u00c15% of co-infection rate was reported with immunofluorescence kit. These variations might be attributed to geographic differences, diagnostic methods for viral agents and study design. 12, 32, 34, 41, 42 Pathogens in those negative patients need to be further investigated Title: Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012\u20132013: A PCR/Electrospray Ionization Mass Spectrometry Study", "Passage: and PCR/ESI-MS. Throat swabs from 15 patients with bacterial infections and 27 individuals without active infections were included as control samples. Respiratory viruses were found in 23.6%, 47.2%, and 47.9% of the 267 cases by virus isolation, PCR/ESI-MS, and both methods, respectively. When both methods were used, the influenza A virus and rhinoviruses were the most frequently identified viruses, whereas human coronaviruses, human metapneumovirus , enteroviruses, adenoviruses, respiratory syncytial virus, and parainfluenza viruses were identified in small proportions of cases . Coinfection was observed in 4.1% of cases. In the control group, only 1 sample tested positive for a respiratory Title: Volatile fingerprinting of human respiratory viruses from cell culture", "Passage: Infections of the lower respiratory tract, including both influenza and pneumonia, are among the top 10 leading causes of death in the United States , and pneumonia remains one of the world's leading causes of death for children under the age of five . According to the Centers for Disease Control and Prevention , approximately 30% of acute respiratory infections of viral etiology in the United States are inappropriately treated with antimicrobial therapies that are not effective against viral pathogens . Furthermore, it is estimated that a causative pathogen is identified in only approximately 40% of pneumonia cases overall, and", "Title: Genetic diversity and molecular epidemiology of human rhinoviruses in South Africa\nPassage: were not eligible for enrolment. Title: Stakeholder views on the acceptability of human infection studies in Malawi", "Passage: Inclusion and exclusion criteria for HIS participants were seen as an important consideration for acceptability among all stakeholder groups. Participants in focus groups and interviews were asked openly about criteria they saw as important and for their views on criteria being considered by the MARVELS team. Views on groups of who should be either targeted for participation or excluded reflected concerns related to informed and voluntary participation, community interest and misconceptions, equitable opportunities for participation between different population groups, burden on livelihoods or other activities, and ensuring research value and validity through a sample population considered relevant and unbiasedprinciples that Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: Should more than a third of the expected household members refuse to participate, the particular household will be excluded from the study. However, this will not apply if members are away from the household for extended periods due to work or school. Title: Stakeholder views on the acceptability of human infection studies in Malawi\nPassage: \"If we say that participants should be determined by a certain level of education, we are being biased. Someone may be able to understand but not be educated to the standards you want.\"", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: There are limited studies using AAVs as vaccine vectors for influenza. An AAV expressing an HA antigen was first shown to induce protective in 2001 . Later, a hybrid AAV derived from two non-human primate isolates was used to express influenza NP and protect against PR8 challenge in mice . Most recently, following the 2009 H1N1 influenza virus pandemic, rAAV vectors were generated expressing the HA, NP and matrix 1 proteins of A/Mexico/4603/2009 , and in murine immunization and challenge studies, the rAAV-HA and rAAV-NP were shown to be protective; however, mice vaccinated with rAAV-HA + NP + M1 had Title: Viral vector-based influenza vaccines", "Passage: being made to AAV to increase immunogenicity. 220 A limited number of studies evaluating AAV as a vector for influenza vaccination has been performed . Initially, an AAV expressing the HA gene or NP gene was shown to be protective in mice. 221, 222 A more recent study tested AAV vaccines expressing the HA, NP or M1 genes of H1N1pdm09 in mice. Whereas AAV-HA afforded full protection from H1N1pdm09 infection, AAV-NP protected mice partially and AAV-M1 did not afford protection. Simultaneous vaccination with all 3 constructs afforded protection from homologous challenge infection. 223 Recently, in an alternative vaccination approach, AAV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: the most robust protection. Also, mice vaccinated with rAAV-HA + rAAV-NP + rAAV-M1 were also partially protected against heterologous challenge . Most recently, an AAV vector was used to deliver passive immunity to influenza . In these studies, AAV was used to deliver an antibody transgene encoding a broadly cross-protective anti-influenza monoclonal antibody for in vivo expression. Both intramuscular and intranasal delivery of the AAVs was shown to protect against a number of influenza virus challenges in mice and ferrets, including H1N1 and H5N1 viruses . These studies suggest that rAAV vectors are promising vaccine and immunoprophylaxis vectors. To this Title: Viral vector-based influenza vaccines", "Passage: Adeno-associated virus is a parvovirus that is replication-deficient in humans. Like adenovirus, AAV has a broad cell, tissue and host tropism and therefore is a potential good vector vaccine. 218 However, drawbacks of using AAV include: limited capacity for transgenes, presence of pre-existing immunity in humans and the technical challenge of producing high titer stocks. Initially, AAV was not explored as a vaccine vector as it was considered to be poorly immunogenic, however vaccination studies in mice showed that AAV-2 expressing an HSV-2 glycoprotein was immunogenic and a potent inducer of Tcell and antibody responses, 219 and currently modifications are", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: additional studies or reports not retrieved by the initial searches. Studies that examined the mechanisms of diagnostic tests, drug therapy or vaccine efficacy against SARS, MERS and 2019-nCoV were excluded. A Google search for 2019-nCoV diagnostics yielded five webpage links from government and international bodies with official information and guidelines , three webpage links on diagnostic protocols and scientific commentaries, and five webpage links on market news and press releases. Six protocols for diagnostics using reverse transcriptase polymerase chain reaction from six countries were published on WHO's website . Google search for 2019-nCoV vaccines yielded 19 relevant articles. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: There are eleven studies that focus on SARS-CoV diagnostic testing . These papers described diagnostic methods to detect the virus with the majority of them using molecular testing for diagnosis. Comparison between the molecular test and serological test showed that the molecular test has better sensitivity and specificity. Hence, enhancements to the current molecular test were conducted to improve the diagnosis. Studies looked at using nested PCR to include a pre-amplification step or incorporating N gene as an additional sensitive molecular marker to improve on the sensitivity . Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: Clinicians working with local public health departments must arrange to have specimens from patients under investigation sent to the CDC laboratory. At this time, the CDC has the only laboratory that can definitively test for 2019-nCoV, though laboratory testing capacity is being rapidly expanded. Polymerase chain reaction assays conducted on samples from a patient's upper and lower respiratory tracts will be used to confirm potential cases. In addition, serum antibody titers can be analyzed for confirmation of infection or evidence of immunity. Up-to-date information about the needed specimens and handling requirements to test for 2019-nCoV are available on the CDC Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s ; with bacterial infections previously considered as the likely culprit for acute exacerbation . However, with the advent of PCR technology, more viruses were recovered during acute exacerbations events and reports implicating their role emerged in the late 1980s . Rhinovirus and respiratory syncytial virus are the predominant viruses linked to the development and exacerbation of chronic airway inflammatory diseases . Other viruses such as parainfluenza virus , influenza virus and adenovirus have also been implicated in acute Title: Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits", "Passage: In this study, the commonly identified viruses in patients with COPD exacerbations requiring ED visits were PIV3, Inf A virus, and human rhinovirus. This result was similar to the finding of Cameron et al from a study in Australia in which the most frequently detected viral etiologies were Inf A, PIV3, and rhinovirus. 21 In a recent review of eight studies, picornavirus was the most common virus in western countries and influenza virus was most common in Asia. 7 H. influenzae was the most common bacterial pathogen in COPD exacerbations in a previous study. 4 Pseudomonas aeruginosa and Klebsiella pneumoniae Title: Th17 profile in COPD exacerbations", "Passage: In the past, it was believed that only bacteria were capable of generating exacerbations in patients with COPD. 48, 52 However, the occurrence of these in the winter and symptoms similar to cold led to the belief that viruses were also associated with the complications of this obstructive pathology of the airways. 53 On the other hand, viral infections of the respiratory tract have been shown to influence the lung microbiome in patients with COPD, which indicates that both microorganisms can coexist and predispose to exacerbations. 54 The most prevalent viruses during acute exacerbations of COPD are rhinovirus, coronavirus, influenza,", "Title: Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators\nPassage: for adults, except for certain groups in some countries such as HCWs and pregnant women. The surprisingly higher uptake reported among participants from Oman needs further research to validate, and if confirmed, to explore reasons for this better coverage. The results of studies from Australia and Canada revealed a coverage rate of pertussis vaccine among adults to be around 10%, despite the recommendation of Tdap for those who are likely to come in contact with children, and for pregnant women . Nevertheless, unfortunately findings from other studies show that public health recommendations alone are not enough to increase the vaccination Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: Ltd), scheduled for administration at 6, 10, and 14 weeks, is received with significant delays . These data support the WHO's recommendation that countries using whole cell pertussis vaccine continue to do so given that the majority of outbreaks have been concentrated in countries using the acellular pertussis vaccine . Recent studies suggest that protection from acellular pertussis vaccine is not as strong or long lasting as that conferred by the whole cell pertussis vaccine . Title: Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators\nPassage: Overall, only 16% respondents reported receiving pertussis vaccine, the remaining 84% denied taking the vaccine. The coverage varied very widely across the countries ranging from 7% among Saudi participants to 75% among Omani participants. The uptake of pertussis vaccine among \"at risk\" people was 31% . Title: Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators", "Passage: recommended for individuals with preexisting diseases and elderly adults , and pertussis vaccine is generally advised for HCWs and pregnant women.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: The proposed method called FPASSA is a hybrid of FPA and SSA, in which the SSA is applied as a local search method for FPA. The proposed FPASSA starts by receiving the historical COVID-19 dataset. Then a set of solutions is generated where each of them represents the value for the parameters of the ANFIS model. Then the quality of each solution is calculated using the fitness value, and the solution that has the best fitness value is chosen to represent the best solution. Then the probability of each solution is computed. Then the current solution will be updated, either Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: The rest of this study is organized as follows. The preliminaries of ANFIS, FPA, and SSA are described in Section 2. Section 3 presents the proposed FPASSA, and Section 4 presents the experimental setup and results. We conclude this study in Section 5. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: After finishing the training phase, the testing phase is started with the best solution to compute the final output. The performance of the proposed method is evaluated by comparing the real data with the predicted data using the performance measures. Finally, the FPASSA produces a foretasted value for confirmed cases of COVID-19 in China in the next day. The steps of the proposed FPASSA are presented in Algorithm 1. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: In this section, the performance of the proposed FPASSA to predict the DS1 and DS2 is discussed. It can be concluded from Table 3 that the performance of FPASSA outperformed the compared methods in all measures, whereas the FPA is ranked second. The results of DS2 indicate that the FPASSA is ranked first in terms of RMSE, MAPE, R 2 , and the CPU time. Whereas, the PSO is ranked second, followed by the FPA, GA, then ABC. These results denote that the proposed method can optimize the parameters of the ANFIS model effectively and produce good results in terms", "Title: CDC Summary 21 MAR 2020,\nPassage: cases in the United States by age group found that 80% of deaths were among adults 65 years and older with the highest percentage of severe outcomes occurring in people 85 years and older. Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years . Title: Clinical characteristics and outcomes during a severe influenza season in China during 2017\u20132018\nPassage: in the 14-59 and > 60 groups. Title: Global Mortality Impact of the 1957\u20131959 Influenza Pandemic", "Passage: Age-specific excess mortality rates were highest at both extremes of the age spectrum . However, when excess mortality was compared to baseline mortality rates, the age groups with highest relative burden were 15-24 years , followed by 5-14 years . In contrast, children aged <5 years and seniors aged \u226565 years only experienced a minor elevation over baseline . The sharp mortality elevation in schoolaged children and young adults was consistent throughout Europe , even though the all-age impact of the pandemic on mortality was generally low in this region.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: A single study has examined the ability of MERS-CoV to survive in the environment . Plastic or steel surfaces were inoculated with 10 6 TCID 50 of MERS-CoV at different temperature and relative humidity and virus recovery was attempted in cell culture. At high ambient temperature and low RH MERS-CoV remained viable for 24 h . By comparison, a well known and efficently transmitted respiratory virus, influenza A virus, could not be recovered in culture beyond four hours under any conditions . Aerosol experiments found MERS-CoV viability only decreased 7 % at low RH at 20\u00b0C. In comparison, influenza A Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: virus decreased by 95 % . MERS-CoV survival is inferior to that previously demonstrated for SARS-CoV . For context, pathogenic bacteria can remain viable and airborne for 45 min in a coughed aerosol and can spread 4 m. MERS-CoV's ability to remain viable over long time periods gives it the capacity to thoroughly contaminate a room's surfaces when occupied by an infected and symptomatic patient . Whether MERS-CoV can remain adrift and infectious for extended periods remains unknown. Such findings expand our understanding of the possibilities for droplets to transmit respiratory viruses in many settings, including hospital waiting rooms, emergency Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Individual human case studies report long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms. In one instance, a HCW shed viral RNA for 42 days in the absence of disease . It is an area of high priority to better understand whether such cases are able to infect others. Over three quarters of MERS cases shed viral RNA in their LRT specimens for at least 30 days, while only 30 % of contacts were still shedding RNA in their URT specimens . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: families and healthcare settings . Clinical pictures of this infection varied from asymptomatic to mild respiratory symptoms to severe respiratory distress and death . Severe ailment can often cause respiratory catastrophes that need mechanical ventilation and support in ICUs across different healthcare settings . Studies have suggested an incubation period of 16 days with a mean of 5-6 days , while the median time until death is 11-13 days among severely ill patients . e gold standard test for the detection of this virus is real-time reverse-transcription polymerase chain reaction assays .", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: After application of the overlay, plates were monitored periodically using an inverted fluorescence microscope until the first signs of GFP expression were witnessed . From that time forward, a square subset of the center of each well was imaged periodically, using a CellInsight CX5 High Content Screening Platform with a 4X air objective . Microscope settings were held standard across all trials, with exposure time fixed at 0.0006 s for each image. One color channel was imaged, such that images produced show GFP-expressing cells in white and non-GFP-expressing cells in black . Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: Because plaque assays restrict viral transmission neighbor-to-neighbor in two-dimensional cellular space , we were able to track the spread of GFP-expressing virus-infected cells across tissue monolayers via inverted fluorescence microscopy. For each infection trial, we monitored and re-imaged plates for up to 200 hr of observations or until total monolayer destruction, processed resulting images, and generated a time series of the proportion of infectious-cell occupied plate space across the duration of each trial . We used generalized additive models to infer the time course of all cell culture replicates and construct the multi-trial dataset to which we eventually fit our Title: Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy", "Passage: express cytoplasmic fluorescent proteins driven e.g., by the chicken \u03b2-actin promoter with cytomegalovirus enhancer or human ubiquitin C promoter . Many different mouse lines are available that contain reporter genes for cytoplasmic fluorescent proteins such as EGFP and mCherry . Due to strong and continuous expression rate of the fluorescent proteins long-term tracking of dividing cells without extensive bleaching is possible. In addition, with a superior signal-to-noise ratio visualization of small cellular structures with low cytoplasm content is feasible. Although the approach to adoptively transfer fluorescent cells of interest into donor mice for functional imaging studies is fast and flexible, Title: Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy", "Passage: Recently, MP-IVM was used to study the mechanism of retrovirus spread in vivo within secondary lymphoid tissues by visualizing MLV-infected cells and MLV particles directly in living animals. In a first study, in vitro transduced B cells were adoptively transferred into mice for MP-IVM at the popliteal lymph nodes . In contrast to other studies visualizing infected cells expressing cytoplasmic GFP after reporter virus infection, full-length MLV encoding for a capsid fusion with GFP helped to analyze the subcellular distribution of a structural retroviral protein in vivo. MLV Gag-GFP revealed a polarized distribution in static MLV-infected cells indicating the existence", "Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations", "Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: should be considered everyone's problem. The recent Zika virus epidemic followed many similar patterns highlighting that we all share the responsibility in responding to infectious outbreaks. Many of the country-level factors, particularly the WHO key indicators were associated with controlling the epidemic. International political and public health leaders should assess the infrastructure of countries affected by communicable diseases. Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak", "Passage: This study is subject to certain limitations. Perhaps the most substantial of which is the difficulty to quantify many factors affecting control of the outbreak. For example, the West African people educated their communities, facilitating the change of social practices, such as greetings with physical contact and modifying long-standing traditional burial practices . Education messages on fighting the epidemic were communicated through messaging in radio, billboards, etc. Title: Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases", "Passage: Emerging and re-emerging infectious diseases pose some of the greatest health risks to human populations worldwide. Increasingly they are a feature of our time, stoked by changes in human demographics, mobility, land use and climate, and compounded by poor standards of public health in parts of the world . Importantly, new surveillance and intervention strategies are now becoming possible, guided by quantitative interpretation of epidemiological data, potentially strengthening the hand of primary prevention efforts. Title: Preventing Emerging and Re-emerging Infections in the Eastern Mediterranean Region: Gaps, Challenges, and Priorities", "Passage: According to the International health regulations of 2005, strengthening or promoting surveillance and response capacities, points of entry capacities, legislation issues, coordination among various national key partners, bio-risk and bio-security and quality management in laboratories are necessary . Strengthening routine vaccination coverage will continue to be the top priority. The Region will focus on improving national managerial capacity and human resource capacity building, empowering decision-making, and supporting countries to reach unreached targets through various evidence-based approaches. Strengthening the monitoring and evaluation systems to use data for action will be among the priority activities. Similarly, strengthening the Regional surveillance networks in", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: Host resilience to emerging coronaviruses", "Passage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\". Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: MERS-CoV was found and characterized because of its apparent association with severe, and therefore more obvious, illness in humans; we were the canaries in the coal mine. Sero-assays and prospective cohort studies have yet to determine the extent to which milder or asymptomatic cases contribute to MERS-CoV transmission chains. However, transmission of MERS-CoV is defined as sporadic , intra-familial, often healthcare associated, inefficient and requiring close and prolonged contact In a household study, 14 of 280 contacts of 26 MERS-CoV positive index patients were RNA or antibody positive; the rate of general transmission, even in outbreaks is around 3 %", "Title: Oxidative Stress in Poultry: Lessons from the Viral Infections\nPassage: The theory of oxidative stress existed since the last 60 years. However, extensive research in the last three decades has clarified myriads of misconceptions and explored leading roles of oxidative stress in the pathogenesis of many viral diseases . A wide range of the reactive species is produced as a result of the metabolic process in the body. These RS can be reactive oxygen species or reactive nitrogen species . Previously, RS were only considered to be toxic compounds: however, recent studies have highlighted their involvements in complex cellular signaling pathways and have improved their importance in several biological systems Title: Oxidative Stress in Poultry: Lessons from the Viral Infections", "Passage: Owing to the production-dependent oxidative stresses, exploring the molecular mechanisms of ROS production in living organisms is imperative. ROS are primarily produced from the mitochondria, endoplasmic reticulum, plasma membrane, and peroxisomes . Since most of the oxidative processes take place in the mitochondria in an effort to generate energy ), more than 90% of total ROS in eukaryotes is produced by the mitochondria . In the living organisms, most of the consumed oxygen is converted to water in the electron-transport chain by the cytochrome c oxidase without any contribution to ROS production . These ROS include superoxide anion , hydroxyl Title: The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease", "Passage: There are also several metabolic parameters and complications, which are dysregulated in obesity, and contribute to and amplify oxidative stress. Hyperglycemia induces oxidative stress through activation of the polyol and hexosamine pathways, production of advanced glycation end-products , and increase of diacylglycerol synthesis. Hyperlipidemia induces ROS formation by increasing lipid oxidation and protein carbonylation. Leptin and angiotensin II, both of which are secreted by adipocytes, are inducers of ROS generation. Leptin promotes inflammation and lipid peroxidation, while angiotensin II stimulates AT1R-NADPH oxidases. Dysregulation of all of these metabolic parameters with adipose tissue expansion contributes to oxidative stress . increases selectively Title: Oxidative Stress in Poultry: Lessons from the Viral Infections", "Passage: complex . This process of ROS production is critical to promote cellular responses . The O 2 \u2212 , produced by the immune cells, can lead to the formation of other ROS such as HOCl, H 2 O 2 , peroxynitrite , and OH . The OH radicals are produced from O 2 \u2212 by Fenton reaction -). Another possible mechanism is the triggering of ROS production by the virus-induced cytokines. Taken together, ROS may be generated from the activation of XO, NADPH oxidase, lipoxygenases, and cyclooxygenase or from the leakage of electrons from ETC .", "Title: A novel framework for inferring parameters of transmission from viral sequence data\nPassage: of neutral genetic markers has shown that the transmission bottleneck is dependent upon the route of transmission, whether by contact or aerosol transmission . In natural human influenza populations, where modification of the virus is not possible, population genetic methods have been used to analyse bottleneck sizes. Analyses of transmission have employed different approaches, exploiting the observation or non-observation of variant alleles or using changes in allele frequencies to characterise the bottleneck under a model of genetic drift . A recent publication improved this latter model, incorporating the uncertainty imposed upon allele frequencies by the process of within-host growth . Title: Insights into the transmission of respiratory infectious diseases through empirical human contact networks", "Passage: In fact, the influenza spreading behavior can be clearly divided into two categories: in the US schools, disease outbreak appears to be relatively strong and early ; in the schools of SCAU, USTB as well as FRPS, a considerably low transmission was observed . Title: Transmission Dynamics and Prospects for the Elimination of Canine Rabies", "Passage: Transmission is the most important process underlying infectious disease dynamics , but it is also the least understood. Rates of transmission are usually inferred from population patterns of disease incidence, but populationlevel analyses do not capture between-individual variation in transmission resulting from differences in behaviour, genetics, immune status, and environmental and stochastic factors, which play an important role in determining disease dynamics . Contact tracing has been used to directly measure case-to-case transmission, and applications of the technique to emerging infections such as SARS have generated important insights into disease transmission and control in human populations , but transmission processes Title: A novel framework for inferring parameters of transmission from viral sequence data", "Passage: Viral transmission is a critical component of disease and a key factor in viral evolution. In outlining a novel framework for the interpretation of data from viral transmission events we hope to bring a greater clarity to the population genetic theory of how these events operate and a greater power in the interpretation of experimental data, so as to engender a greater understanding of this important topic of research.", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: deoxyribozymes can form from ribonucleotides . Thus, DNA can arise from RNA chemically, without the key protein enzyme, the reverse transcriptase. Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: The selected ribozymes were able to replicate, cleave, join, and form peptide bonds. They can polymerize progeny chemically, allow for mutations to occur and can evolve. One molecule serves as catalyst, the other one as substrate. Replication of ribozymes was demonstrated in the test tube . Ribozymes can form peptide bonds between amino acids . Thus, small peptides were available by ribozyme activity. Consequently, an RNA modification has been proposed as peptide nucleic acid , with more stable peptide bonds instead of phosphodiester bonds . Replication of RNA molecules can be performed chemically from RNA without polymerase enzymes. In addition, Title: The elusive quest for RNA knots", "Passage: even during the origins of life. The RNA world concept posits a period of time when RNA, or something chemically similar, was responsible for all living processes including heredity and metabolism. RNA-RNA interactions have often been proposed to be critical to maintaining the physical integrity of networks of distinct sequences. Typically these interactions have focused solely on secondary structure interactions, but many environments on an early Earth could have experienced rather extreme temperature fluctuations that could disrupt weak basepairing. More severe entanglements such as knotsbut without covalent bondingwould have been a means to preserve spatial sympatry of RNA network individuals Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: These studies raise the question of how RNA molecules can become longer, if the small polymers become smaller and smaller, replicate faster and outcompete longer ones. This may be overcome by heat flow across an open pore in submerged rocks, which concentrates replicating oligonucleotides from a constant feeding flow and selection for longer strands. This has been described for an increase from 100 to 1,000 nucleotides in vitro. RNA molecules shorter than 75 nucleotides will die out . Could a poor environment lead to an increase of complexity? This could be tested. Ribozymes were shown to grow in size by", "Title: Interplay between cost and effectiveness in influenza vaccine uptake: a vaccination game approach\nPassage: The case \u03b2 A > \u03b2 B leads to infection dominance of influenza A over B virus . This situation can be controlled by TIV vaccine alone as it targets two strains of A virus. Individuals would then mostly prefer TIV vaccine over QIV vaccine as the price of TIV is lower than the price of QIV . As a consequence, we perceive the sensitivity of choosing TIV vaccine only along the direction of C T . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: The general types of influenza vaccines available in the United States are trivalent inactivated influenza vaccine , quadrivalent influenza vaccine , and live attenuated influenza vaccine . There are three types of inactivated vaccines that include whole virus inactivated, split virus inactivated, and subunit vaccines. In split virus vaccines, the virus is disrupted by a detergent. In subunit vaccines, HA and NA have been further purified by removal of other viral components. TIV is administered intramuscularly and contains three or four inactivated viruses, i.e., two type A strains and one or two type B strains. TIV efficacy is measured by Title: Innate Immune Sensing and Response to Influenza", "Passage: A comparative study of immune response to trivalent inactivated influenza vaccine and live attenuated influenza vaccine using systems biology approach revealed salient common as well as contrasting features between them. While LAIV induced the expression of several interferon-related genes, which are similar to live viral vaccines, the TIV induced a signature composed of genes highly expressed in plasma B cells . For TIV, of the 44 genes identified to accurately predict the outcome of immunization as either high or low antibody titers, one gene-CAMKIV-had no known function in regulating immunity, but was negatively correlated with antibody titers. Consistent with this, Title: Evaluation of Approaches to Identify the Targets of Cellular Immunity on a Proteome-Wide Scale", "Passage: For the in vivo evaluation of IVTT products, mice were immunized intramuscularly with 50 mg/100 ml of VR2516 PyCSP DNA vaccine and boosted 3 weeks later with PyCSP IVTT products formulated with 100 ml Aluminium Hydroxide gel adjuvant as follows: A) 15 ml of IVTT reaction ; B) 15 ml of IVTT reaction purified through NI-NTA resin ; C) 15 ml of IVTT reaction purified through MagneHis Protein Purification System ; D) 15 ml of IVTT reaction absorbed in 10 ml of PolybeadH Poly microspheres ; and E) 15 ml of IVTT reaction associated to 10 ml of Protein G", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: One drawback of an Ad5 vector is the potential for preexisting immunity, so alternative adenovirus serotypes have been explored as vectors, particularly non-human and uncommon human serotypes. Non-human adenovirus vectors include those from non-human primates , dogs, sheep, pigs, cows, birds and others . These vectors can infect a variety of cell types, but are generally attenuated in humans avoiding concerns of preexisting immunity. Swine, NHP and bovine adenoviruses expressing H5 HA antigens have been shown to induce immunity comparable to human rAd5-H5 vaccines . Recombinant, replication-defective adenoviruses from low-prevalence serotypes have also been shown to be efficacious. Low prevalence Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: Experimental adenovirus-based vaccine vectors are promising alternatives to conventional vaccine platforms. In particular, human adenovirus serotype 5 vectors are well-characterized and are being developed against several infectious disease models including influenza, hepatitis C, dengue and viral hemorrhagic fever viruses . Several candidates have demonstrated unique protective efficacy and can generate robust immune responses in both animal models and clinical trials . Pre-existing immunity against AdHu5 is, however, frequent in the human population and has been associated with undesirable clinical outcomes and the suspension of clinical trials . One promising alternative is the development and evaluation of rare human, chimpanzee, or Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: To obtain AdHu5-HA vaccine, HEK 293 cells were transfected with 10 mg of linearized pAdenoX-HA DNA in calcium phosphate solution and cells were cultured until the appearance of cytopathic effects . Similarly, VR1BL E1 cells were transfected with 10 ug of linearized pFPAV227-HA DNA combined with Lipofectin and cells were cultured until CPE were apparent. Amplified adenoviruses containing cell lysates were harvested, freeze-thawed three times, and purified by CsCl gradients. The integrity of the H05-HA transgene cassette was confirmed through EcoRI restriction digests and by sequencing with multiple primer sets. Total virus particles was determined by OD260 and total infectious Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: points. Although not explored in the current study, previous studies have evaluated the impact of pre-existing immunity to PAV3 and the potential reuse of PAV3-based vectors against different pathogens. Groups of outbred pigs with high PAV3 neutralizing antibody titres were vaccinated with a PAV3-based vaccine and vector re-administration did not result in hepatotoxicity or reduced transgene expression . Doses of 10 13 particles/kg AdHu5 vector can also bypass pre-existing immunity, however, several pathologies including liver damage indicated by elevated transaminase, low platelets count, and lymphocytopenia were observed in nonhuman primates administered similar doses .", "Title: Protocol for development of a risk assessment tool for planning and management of religious mass-gathering events of India\u2014a health system-strengthening initiative\nPassage: for other types of MGs ; therefore, restriction of their use mitigated the associated illnesses. In the context of limited resources, it has been suggested that one can choose to alleviate more likely events even if their potential impacts are smaller. Events that are catastrophic, but extremely unlikely, can then be given less priority . During religious gatherings in India, some special events and unforeseen events occur at the places of religious MGs besides fixed places of worshipping. Special events like idol procession, chariot pulling, fire walking, and animal sacrificing happen pulling larger crowds within the MGs and causing more Title: Accuracy of using automated methods for detecting adverse events from electronic health record data: a research protocol", "Passage: number of AE negative patients required, assuming the worst case scenario. Title: Innovations in research ethics governance in humanitarian settings\nPassage: Implementation of this new policy will start in 2014, including submission of generic survey protocols to the ERB. Title: Estimating the number of infections and the impact of non-\nPassage: banned The government bans all public events.39 9/3/2020", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: The first three cases detected were reported in France on 24 January 2020 and had onset of symptoms on 17, 19 and 23 January respectively . The first death was reported on 15 February in France. As at 21 February, nine countries had reported cases : Belgium , Finland , France , Germany , Italy , Russia , Spain , Sweden and the UK . Title: The origins of the great pandemic", "Passage: A second location, from which the influenza outbreak may first have been reported, is to be found in northern France. Lt J.A.B. Hammond and two colleagues encountered an outbreak of 'purulent bronchitis' in late 1916 and early 1917 at a hospital centre forming part of the British army encampment at Etaples. An initial paper was published by this group in The Lancet in July 1917 . This publication precipitated a rapid follow-up article, also in The Lancet, from an independent military group reporting similar observations at Aldershot, in the south of England . Looking back 2 years later, this second Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: The name Spanish flu comes from the first news reports of influenza-like-illness in Madrid in the late spring of 1918. However, this pandemic gained its nickname because the first mentions of the virus were published in Spain, where the press faced no censorship during World War I, owing to the country's neutrality . Many people fell ill with respiratory symptoms in May 1918, including King Alfonso XIII, which was well documented in the press . Because respiratory disease outbreaks occurred in neighboring France as early as April 1918, it is likely that the virus was introduced into Spain via Spanish Title: Estimating the number of infections and the impact of non-\nPassage: 31. The Local. France bans gatherings of more than 100 people as coronavirus death toll rises -", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: or worse, and secondary bacterial infections have been reported . Disease can progress to acute respiratory distress syndrome and multiorgan system failure . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported . General supportive care is key to managing severe cases . Children under Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: Host resilience to emerging coronaviruses", "Passage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\". Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5", "Title: Techniques to Study Antigen-Specific B Cell Responses\nPassage: For HIV-1, the discovery of broadly neutralizing antibodies that protect against infection across diverse viral isolates has intensified efforts to understand the developmental pathway of the rare B cells that produce these antibodies . Insights into the ontogeny of these rare B cells could allow the design of a step-wise vaccine regimen that stimulates the germ-line precursor to expand and mature to produce circulating bnAbs which could protect against HIV acquisition . For RSV, stabilized versions of the fusion protein in the pre-fusion conformation have led to insights in the B cell's response to infection and has generated potentially safer Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: For HIV-1, the discovery of broadly neutralizing antibodies that protect against infection across diverse viral isolates has intensified efforts to understand the developmental pathway of the rare B cells that produce these antibodies . Insights into the ontogeny of these rare B cells could allow the design of a step-wise vaccine regimen that stimulates the germ-line precursor to expand and mature to produce circulating bnAbs which could protect against HIV acquisition . For RSV, stabilized versions of the fusion protein in the pre-fusion conformation have led to insights in the B cell's response to infection and has generated potentially safer Title: Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals", "Passage: Given the predicted low-titer inoculum driving HIV-1 sexual transmission, a vaccine capable of eliciting antibodies that neutralize a broad spectrum of viral strains could potentially reduce or prevent infection. It has been anticipated that the identification of broadly neutralizing mAbs from HIV-1 infected individuals, and the characterization of their cognate epitopes will be instrumental in the design of immunogens capable of eliciting such a broad neutralizing response . This idea has led to a major international cooperative effort within consortia of laboratories with complementary expertise in human immunology, structural biology and vaccine design . Title: Wide Prevalence of Heterosubtypic Broadly Neutralizing Human Anti-Influenza A Antibodies", "Passage: vaccinees , or bone marrow of H5N1-infected ''bird-flu'' survivors . BnAbs with similar properties have also been recovered from immortalized IgGexpressing memory B cells of seasonal vaccinees . An unexpected finding from these studies is the frequent contribution of VH1-69 heavy chain genes to these BnAbs, suggesting that a large fraction of the human naive B cell repertoire has the capability of responding to this conserved epitope . These observations raise additional questions as to whether such BnAbs are present in human serum and at ''protective'' levels, whether they exist as ''natural'' Abs, and/or whether are they generated during the", "Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy\nPassage: AP3 had longer half-life than T20. Although T20 has shown efficacy in inhibiting HIV-1 infection, its major weakness lies in its short half-life in plasma . As a result, T20 has to be administered subcutaneously twice daily at 90 mg per dose, often causing serious injection-site reactions 25, 26 . Here, we performed pharmacokinetic studies by intravenous administration of AP3, AP2, and T20, respectively, to SD rat at a dose of 1 mg/kg, in order to compare their in vivo circulation time. As expected, T20 exhibited a shorter half-life and lower AUC from systemic circulation, while AP3 and AP2 demonstrated Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: AP3 had longer half-life than T20. Although T20 has shown efficacy in inhibiting HIV-1 infection, its major weakness lies in its short half-life in plasma . As a result, T20 has to be administered subcutaneously twice daily at 90 mg per dose, often causing serious injection-site reactions 25, 26 . Here, we performed pharmacokinetic studies by intravenous administration of AP3, AP2, and T20, respectively, to SD rat at a dose of 1 mg/kg, in order to compare their in vivo circulation time. As expected, T20 exhibited a shorter half-life and lower AUC from systemic circulation, while AP3 and AP2 demonstrated Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: much higher concentration and longer circulation time . The pharmacokinetic profiles of AP3 and AP2 fit a non-compartment model. The pharmacokinetic parameters were calculated with PK Solver. The in vivo elimination half-life of AP3 was about 2.8-fold longer than that of T20 . This result provided the theoretical basis for reducing the injection frequency and dose of the fusion inhibitor, in conjugation with the improved antiviral potency of AP3. Therefore, replacement of T20 with AP3 may significantly reduce injection-site reactions and the drug cost, which would promote the clinical applications of the HIV fusion inhibitor in resource-poor regions or countries. Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: much higher concentration and longer circulation time . The pharmacokinetic profiles of AP3 and AP2 fit a non-compartment model. The pharmacokinetic parameters were calculated with PK Solver. The in vivo elimination half-life of AP3 was about 2.8-fold longer than that of T20 . This result provided the theoretical basis for reducing the injection frequency and dose of the fusion inhibitor, in conjugation with the improved antiviral potency of AP3. Therefore, replacement of T20 with AP3 may significantly reduce injection-site reactions and the drug cost, which would promote the clinical applications of the HIV fusion inhibitor in resource-poor regions or countries.", "Title: Antibody Engineering for Pursuing a Healthier Future\nPassage: Dot Blot assays are used to measure protein concentrations semi-quantitatively. It is slightly different from the WBA. Proteins in the sample are not separated by electrophoresis but are spotted directly on a membrane and hybridized with an antibody probe . This technique is cost effective and uses avidin-biotin technology with diaminobenzidine as a chromogen. It is used for the analysis and quantitation of 14-3-3 protein in cerebrospinal fluid samples from cases of Creutzfeldt-Jakob disease , and for disease control of other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease . Title: Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening", "Passage: technologies allow changes in the localization of GFP-tagged proteins, in response to small molecules, to be detected at the subcellular level in living cells cultured in 384-well plates. Therefore, GFP is suitable as both a reporter of transcriptional activation, and of functional protein translocation in the cell, in response to various stimuli. Title: Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening", "Passage: the blood stream in animals. Some intra-and extracellular reporter gene assays may detect the reporter protein's activity without killing the cells or animals in which the assay is performed. This allows time-course experimentation by sampling of the medium of cultured cells, or the blood plasma of research subjects. As such, report bioassays are potentially suitable for high throughput screening of small molecule drug candidates. Bioassays are used to determine the concentration or biological activity of molecules such as hormones, growth factors, and enzymes. Moreover, they can be used for measuring the effects of candidate drugs on an organism, cultured cells, Title: Animal board invited review: advances in proteomics for animal and food sciences", "Passage: second-dimensional molecular sieving by molecular mass . After staining with visible/colorimetric or fluorescent dyes, protein spots are detected and evaluated in abundance by means of dedicated software. Alternatively, modern methods of pre-electrophoretic protein labelling with fluorescent dyes allow direct detection of separated protein spots . Protein spots of interest, usually those that vary in intensity in a treatment-or disease-dependent comparison, are enzymatically digested into peptides. On the basis of their size and fragmentation pattern, subsequent MS analysis attributes them to particular proteins, aided by computer-based search in dedicated large databases.", "Title: Modeling the effect of comprehensive interventions on Ebola virus transmission\nPassage: containment strategy, usually inefficient 33 . This agrees with the estimate of \uf0f2 in Table 1 , which is not small, implying that isolated individuals still have a high capacity to transmit the virus. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: number and finally be helpful to control the transmission. Title: Modeling the effect of comprehensive interventions on Ebola virus transmission\nPassage: limit the contact with isolated individuals. Title: Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour", "Passage: Many strategies, such as mask wearing , ventilation , hand washing and surface cleaning , can limit the spread of influenza A in a confined room. Wearing a mask can control the spread of disease via the long-range airborne, fomite and close contact routes. A high ventilation rate helps to dilute the virus concentration in the air, and the respiratory dose from the long-range airborne route will be obviously reduced. Hand washing can reduce the infection risk directly via fomites and indirectly via the long-range airborne route because of the lower rate of resuspension from surfaces to the air. The", "Title: Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015\nPassage: Influenza epidemics in temperate latitudes are usually characterized by the dominance of influenza B or one of two subtypes of influenza A, A/H3N2 or A/H1N1. Goldstein et al. found that the epidemic sizes of influenza A/H3N2, A/H1N1, and B infections varied from year to year in temperate regions and discovered that type A was the most virulent of the three types of influenza virus and was associated with seasonal epidemics in temperate regions. Rambaut et al. confirmed that the epidemiological data on influenza A demonstrated an inconsistent seasonal pattern of influenza virus infection across years, with high activity during Title: Influenza, evolution, and the next pandemic", "Passage: Influenza A viruses are categorized into two groups. Group 1 includes H1, H2 and H5 subtypes, whereas Group 2 includes H3 and H7 subtypes ). This phylogenetic understanding has informed recent age-specific analyses of mortality patterns before, during and after the 1918 pandemic . Worobey et al. have used a hostspecific molecular clock approach to demonstrate that high mortality in young adults may have been due to childhood exposure to a doubly heterosubtypic putative H3N8 virus that circulated from 1889 to 1900 . They think that young children were protected by childhood exposure to a newly emerged H1variant or N1 Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features", "Passage: Novel strains of infl uenza virus arise due to antigenic shifts and drifts. These strains have very different surface glycoproteins which did not exist in human strains before. A pandemic occurs when such a virus emerges in humans with effi cient human to human transmission. As there is very little or no immunity against it, the virus quickly infects a large number of individuals in all age groups. A pandemic has been expected for long and it was feared that H5N1 avian infl uenza virus which caused severe disease in clusters of humans was the most likely candidate virus to Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features\nPassage: virus genes or by animal to human transmission. A pandemic occurs when a new type of infl uenza A virus is introduced in humans that can cause a serious illness and is capable of sustained human to human transmission.", "Title: Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013)\nPassage: While NMR spectroscopy and X-ray crystallography are the most informative and heavily used methods for understanding protein structure, each has inherent flaws. This is especially evident regarding disordered protein structures, where crystallization requires mostly static structures for diffraction, and NMR is unable to distinguish between different conformational states in an ensemble. Mass spectrometry represents a complementary technique that can be used to generate useful information when examining disordered proteins. Title: Murphy's law\u2014if anything can go wrong, it will: Problems in phage electron microscopy", "Passage: Contrast. Poor contrast seems to be a pervasive, if not the main problem of \"digital\" electron microscopy . Indeed, many \"digital\" micrographs are lamentably dark and poorly contrasted. This is not an intrinsic limitation of \"digital\" microscopes or cameras, but rather due to inappropriate parameters or complete misunderstanding of the dynamic signal range during image acquisition. Title: Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells", "Passage: To observe thicker samples under cryo-conditions without the need to generate sections, soft X-ray cryo-tomography can be also used , reviewed in ). It is a powerful method that takes advantage of the high penetration power of X-rays without using any fixative or contrasting reagent . Its intermediate resolution in comparison with the high resolution of cryo-ET, has limited its use when fine ultrastructural details are needed. However, 15 nm spatial resolution has been already attained with this method . Title: Picornavirus uncoating intermediate captured in atomic detail\nPassage: beamsize of between 0.03 \u00c2 0.03 mm 2 and 0.06 \u00c2 0.07 mm 2 , depending on the size of the crystals. On I24, the X-ray beam was homogenized with a 0.25-mm carbon plate and focused downstream from the crystal. Using 0.1 s exposure times and 100% beam transmission, typically 4-15 useful images could be collected from a crystal .", "Title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection\nPassage: respiratory mucosa may also be involved in the protection against the lethal influenza challenges , even though the exact mechanisms remain to be determined further. The immunization with adenovirus vector encoding NP induced both cellular and antibody responses. It has been shown recently that influenza virus-infected cells can be eliminated by anti-M2e IgG-mediated cellular cytotoxicity or phagocytosis since these cells express M2 on their surface after infection . Similarly, the NP-specific antibodies may interact with the viral NP expressed on cell surface of infected cells and mediate cell lysis by antibody-dependent cellular cytotoxicity. Title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection", "Passage: virus titers at day 5 post-challenge were detected at similar levels in all immunization groups . It is probable that rAd/NP may induce long-lasting innate immunity that contributes complementarily with other specific immune arms to the control of the disease by uncharacterized mechanisms . As a result, the protection may not necessarily correlate with virus titers detected in the lungs upon lethal challenge. Overall, these results indicate that i.n. immunization of rAd/NP can confer complete protection against the lethal homologous virus challenge while allowing competent virus replication to perpetuate even to day 5 post-challenge. Title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection", "Passage: NP-specific serum IgGs and that PR8-challenge following rAd/NP immunization significantly increases PR8-specific serum IgG levels, compared to that of pre-challenge levels, in intranasally immunized mice, but not in sublingually immunized mice. Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: The ability of human adenoviruses to induce strong innate and adaptive immune responses makes them powerful adjuvants that facilitate the immune response against an encoded antigen. Recombinant adenoviruses have been shown to elicit significant immune responses to bacterial , viral and tumour-associated antigens . While these results are encouraging, immunity eventually develops against virus capsid proteins. This severely reduces the immunogenicity of adenovirus-based vaccines in mice, , primates and humans . This problem is also significant since a large portion of the Western world has marked levels of anti-adenovirus serotype 5 antibodies and is also prominent in regions of sub-Saharan", "Title: Estimation in emerging epidemics: biases and remedies\nPassage: The exact relationship between the generation time G and serial interval S is thus model-dependent, but it always holds that they have the same mean. As for the variances, nothing can be said in complete generality. However, for all existing models we are aware of, it holds that V ! V, with equality requiring rather specific assumptions. So, except in specific cases, the observed serial interval distribution will be a biased estimate of the generation time distribution and will have a larger variance. The quantitative effects of using a distribution with equal mean but larger variance than the true one Title: Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic", "Passage: interval is most sensitive to the mean exposed period, 1=s, and thus this is more accurately estimated. Although the parameter estimates from the three models are different, the estimated serial interval distributions corresponding to mean parameter estimates are all very similar , thus so are the mean serial intervals. The fit using N~4 is the best in terms of the mean likelihood. Title: Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic", "Passage: The estimated serial interval distributions and credible intervals are shown in Figure 5 for the two different values of j, along with kernel density plots for the mean serial intervals. In the original analysis a Weibull distribution was fitted and is shown for comparison; the estimated mean serial interval was 3:6 days . From the serial interval distributions we estimate the mean serial interval to be 3:6 days assuming j~2 and 3:8 days assuming j~4. The mean likelihood of the j~4 fit is approximately three times that of the j~2 fit. Figure 6 shows the expected number of serial interval Title: Estimation in emerging epidemics: biases and remedies", "Passage: value which should be less than the true expected generation time, which is 15. Theory again predicts that the backward generation time should have mean 12.57, which is not far from what is observed. The variance of the true generation time is 75 and both variance estimates from the simulation samples tend to be much less, somewhat above 50 . This also leads to the useful conclusion that serial intervals are affected by the same \"contraction\" as generation times when ascertained \"backwards\", at least in the chosen parameter setting.", "Title: Host resilience to emerging coronaviruses\nPassage: Corticosteroids are broadly immunosuppressive and have many physiological effects . Several recent studies have suggested that other compounds could be useful in increasing host resilience to viral lung infections. A recent paper demonstrates that topoisomerase I can protect against inflammation-induced death from a variety of viral infections including IAV . Blockade of C5a complement signaling has also been suggested as a possible option in decreasing inflammation during IAV infection . Other immunomodulators include celecoxib, mesalazine and eritoran . Another class of drugs that have been suggested are statins. They act to stabilize the activation of aspects of the innate immune Title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus", "Passage: The use of statins, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors has been proposed to regulate the IAV-induced cytokine storm in severe infections . Retrospective studies conducted separately in Mexico, Netherlands, UK and USA reported an association of reduced IAV-related pneumonia and lower case fatality due to lower respiratory tract IAV infections with statin treatment . However, this association was contested in two additional studies that found no benefit of statin treatment on IAVinduced disease burden . This uncertainty regarding the IAV therapeutic potential of these widely used compounds warrants further investigations at the basic science level and Title: Statin Treatment and Mortality: Propensity Score-Matched Analyses of 2007\u20132008 and 2009\u20132010 Laboratory-Confirmed Influenza Hospitalizations", "Passage: acute respiratory disease syndrome associated with sepsis . In contrast, a recent in vitro study showed that statin treatment can protect host cells against influenzainduced inflammation by reducing the production of tumor necrosis factor-\u03b1, interleukin-8, and interferon-\u03b3, and therefore inhibit influenza A virus replication . Further studies to evaluate the effect of immunomodulatory agents in reducing influenza-related complications may still be warranted, but they may be better suited for settings where these drugs are not used widely. Title: Key mechanisms governing resolution of lung inflammation", "Passage: 5-7 days postinfection . In the past decade, it has been increasingly recognised that as well as reducing lipid burden and modifying cardiovascular disease, HMG Co-A reductase inhibitors have hitherto unappreciated anti-inflammatory effects that are potentially harnessable for management of inflammatory disease. A recent trial suggested that atorvastatin reduced cough severity in stable bronchiectasis with associated increase in apoptotic neutrophils seen in sputum, and there is renewed interest in their role in modulating acute inflammatory conditions . A recent systematic review examined a number of studies exploring the role of statins in CAP and concluded that they modulate neutrophil response,", "Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity\nPassage: Currently, one urgent and critical challenge is to treat infected patients and save their lives. Several studies have roughly described the overall clinical features of 2019-nCoV patients . However, the more specific and classified clinical characteristics of the infected patients still require further investigation, particularly for those with severe symptoms, which is roughly estimated to be approximately 15-20 percent of totally confirmed cases based on the local data in our hospital. Clinically, for those severe patients, the main symptoms of 2019-nCoV pneumonia are fever, decreased white blood cell and lymphocyte count, increased C reaction protein and abnormally expressed cytokines . Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Those with one of the following pathogenic evidence is the confirmed case: positive for the 2019-nCoV by the real-time PCR test for nucleic acid in respiratory or blood samples . 2) viral gene sequencing shows highly homogeneity to the known 2019-nCoV in respiratory or blood samples . Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Throughout the period of home care, healthcare personnel should perform regular follow-up through face-to-face visits or phone interviews to follow the progress of symptoms and, if necessary, specific diagnostic tests should be conducted . Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: There are eleven studies that focus on SARS-CoV diagnostic testing . These papers described diagnostic methods to detect the virus with the majority of them using molecular testing for diagnosis. Comparison between the molecular test and serological test showed that the molecular test has better sensitivity and specificity. Hence, enhancements to the current molecular test were conducted to improve the diagnosis. Studies looked at using nested PCR to include a pre-amplification step or incorporating N gene as an additional sensitive molecular marker to improve on the sensitivity .", "Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells\nPassage: In 2010, Dr. Yount and co-workers reported that the antiviral activity of IFITM3 is dependent on S-palmitoylation on the protein . The S-palmitoylation is a post-translational modification on proteins by C 16 saturated-fatty acids covalently attached to certain cysteine residues via a thioester linkage . The modification is reversibly catalyzed by protein acyltransferases and acylprotein thioesterases, and confers unique properties to the protein, such as membrane binding and targeting, immunoreactivity, Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: In 2010, Dr. Yount and co-workers reported that the antiviral activity of IFITM3 is dependent on S-palmitoylation on the protein . The S-palmitoylation is a post-translational modification on proteins by C 16 saturated-fatty acids covalently attached to certain cysteine residues via a thioester linkage . The modification is reversibly catalyzed by protein acyltransferases and acylprotein thioesterases, and confers unique properties to the protein, such as membrane binding and targeting, immunoreactivity, Title: The intracellular dynamic of protein palmitoylation", "Passage: but, instead, likely inhibits membrane binding by blocking palmitoylation. This phosphoregulation of palmitoylation might be relevant to many palmitoylated peripheral proteins and could represent a mechanism to promote a shift toward the depalmitoylated state of a protein in the absence of active depalmitoylation. Negatively charged phosphate groups are likely to inhibit palmitoylation of neighboring cysteines by interfering with membrane interactions before palmitoylation . Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: In this study, we investigated the S-palmitoylation of IFITM5 and its role in the interaction with FKBP11 in mouse osteoblast cells. Cells transfected by a plasmid DNA encoding mouse IFITM5 were grown in the presence of an established chemical reporter, 17-octadecynoic acid , or an inhibitor for the S-palmitoylation, 2-bromopalmitic acid . The biochemical assays using these compounds revealed that the wild-type IFITM5 is S-palmitoylated. To identify the Spalmitoylation site in IFITM5, we prepared cysteine-substituted mutants, IFITM5-C86A, -C52A/C53A, and -C52A/53A/86A . The chemical reporter assay suggested that at least two out of three cysteines in IFITM5 are S-palmitoylated. The interaction", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: MVA as a leading viral-vectored candidate vaccine. Title: Virus-Vectored Influenza Virus Vaccines\nPassage: magnitude of the antigen-specific effector functions . MVA is also a potent activator of early innate immune responses further enhancing adaptive immune responses . Between early smallpox vaccine development and more recent vaccine vector development, MVA has undergone extensive safety testing and shown to be attenuated in severely immunocompromised animals and safe for use in children, adults, elderly, and immunocompromised persons. With extensive pre-clinical data, recombinant MVA vaccines expressing influenza antigens have been tested in clinical trials and been shown to be safe and immunogenic in humans . These results combined with data from other clinical and pre-clinical studies support Title: Viral vector-based influenza vaccines", "Passage: MVA holds great promise as a vaccine vector and was initially shown to be a promising influenza vaccine in 1994 by Sutter et al. 37 This vaccine was engineered to express the HA and nucleoprotein gene from influenza virus A/PR/8/34. In addition, recombinant MVA expressing other proteins from various influenza strains were generated and tested in animal models. Title: Viral vector-based influenza vaccines", "Passage: various subtypes of influenza A virus. This vaccination regimen proved immunogenic in pigs, but the protective potential was not tested in this species. 58 An MVA-NPCM1 vaccine was subsequently tested in phase 1/2a clinical trials and was shown to induce virus-specific CD8 C T-cells in humans and protect from experimental challenge infection with an A virus. 58, 60, 61 Furthermore, this vaccination regimen was again shown to be safe and immunogenic in the elderly, 62 and could be co-administered with TIV. 63 Universal influenza vaccines on basis of MVA Because of the variable nature of influenza viruses and the extensive", "Title: Techniques to Study Antigen-Specific B Cell Responses\nPassage: detailed analysis of B cell subsets with pathogenic potential in humans could lead to a better understanding of how to prevent and treat autoimmune diseases. Title: Techniques to Study Antigen-Specific B Cell Responses\nPassage: detailed analysis of B cell subsets with pathogenic potential in humans could lead to a better understanding of how to prevent and treat autoimmune diseases. Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: The study of B cell responses has not only informed vaccine design but has also advanced our understanding of antibodymediated autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus . Up to 20% of mature, na\u00efve B cells have receptors with the capacity to bind self-antigens . Although these cells are potentially pathogenic, the deletion of B cells with high affinity to self-antigen through apoptosis, anergy of B cells with low affinity to self-antigen, and the absence of T cell help combine together to protect against autoimmune disease in mice . The study of autoantigen-specific B cells and a Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: The study of B cell responses has not only informed vaccine design but has also advanced our understanding of antibodymediated autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus . Up to 20% of mature, na\u00efve B cells have receptors with the capacity to bind self-antigens . Although these cells are potentially pathogenic, the deletion of B cells with high affinity to self-antigen through apoptosis, anergy of B cells with low affinity to self-antigen, and the absence of T cell help combine together to protect against autoimmune disease in mice . The study of autoantigen-specific B cells and a", "Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population\nPassage: Of the 29 swabs received, 18 had a corresponding research swab that was positive for a respiratory pathogen. Seven corresponding self-swabs were concordant with the positive research swabs for influenza, and eight corresponding self-swabs were concordant with the research swab for noninfluenza pathogens . The kappa statistic between research and self-swab was 0.84. There were no differences in demographic variables, including education level or days between drop-off and receipt of swabs, among participants whose self-and research-staff obtained swabs correlated versus those whose swabs did not correlate . Of the self-swab samples that had a corresponding positive research swab, the longest Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: the self-swab using the research swab as the gold standard was assessed. All analyses were conducted using SPSS Statistics V22.0 . Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: To assess feasibility, we determined the proportion of households agreeing to perform the self-swab, the proportion returning the swab, and the number of days elapsed between when the participants received the kit and when the swab arrived in the laboratory. All swabs obtained by research staff were analyzed by a commercially available multiplex reverse transcription polymerase chain reaction assay according to the manufacturer's instructions . The assay has a limit of detection of 1-200 tissue culture infective dose 50/mL for influenza, and an LOD of 4-30,000 TCID50/mL for non-influenza viral pathogens, of which only rhinovirus/enterovirus has an LOD of more Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: mailer that followed the US Postal Service guidelines for biological substances. 9 Participants were advised that if the swab was not sent the day it was obtained, it should be stored in the refrigerator. The research staff followed up by telephone the next day to confirm that the self-swab was obtained and sent. Each participant obtaining the self-swab received a round-trip New York City MetroCard when the specimen was received.", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: Text: On 29 December 2019 clinicians in a hospital in Wuhan City, China noticed a clustering of cases of unusual pneumonia with an apparent link to a market that sells live fish, poultry and animals to the public. This event was reported to the World Health Organisation on 31 December . Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine Title: Note from the editors: novel coronavirus (2019-nCoV)", "Passage: Text: The situation has continued to evolve rapidly since then and just a few weeks later, as at 23 January, 614 laboratory-confirmed cases and 17 deaths have been reported including some cases detected outside mainland China . Meanwhile, on 7 January 2020, the novel coronavirus, currently named 2019-nCoV, was officially announced as the causative agent by Chinese authorities . In order to support public health action, viral genome sequences were released by Chinese researchers on 10 January and 2 days later, four further sequences were also made available on the Global Initiative on Sharing All Influenza Data . While more Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir.", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: The identical antibodies used in the ELISA-array format were also tested in a conventional ELISA format to determine the difference in sensitivity and specificity of the two methods. The conventional ELISAs were performed at the same time as the ELISA-array assays to ensure similar reaction conditions. The conventional ELISAs were performed in an identical maner to the ELISA-array, except that antibodies were coated at a concentration of 2 \u03bcg/mL in PBS , and substrate TMB was used instead of Super Signal ELISA Femto Maximum sensitive substrate . Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Antigen binding was performed in PBS at 37\u00b0C for 2 h, followed by washing 3 times. Incubation of ELISA plates with biotinylated detecting antibody cocktails was performed in PBS at 37\u00b0C for 2 h. After washing, specific binding of the detecting antibodies was reported by streptavidin-HRP and stained with Super Signal ELISA Femto Maximum sensitive substrate . Visualization of the plate was performed in AE 1000 cool CCD image analyzer. The signal intensity and background of each spot was read out and recorded with \"Monster\"software. The positive signals were defined as a signal value > 400 and a signal value Title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera", "Passage: All reagents were added to the immunoplates at a volume of 100 \u00b5L/well unless otherwise stated. Passive adsorption onto ELISA plates was performed at 4 \u2022 C overnight and all subsequent incubations were performed at 37 \u2022 C in a humidified chamber for 1 h. Following coating, plates were washed 3 times with 300 \u00b5L of PBS containing 0.1% Tween 20; the same washing procedure followed each subsequent stage of I-ELISAs. Plates were blocked with 200 \u00b5L 10% non-fat milk powder in PBS. After incubation, plates were washed, and control and test sera diluted 1:400 in 2% non-fat milk powder Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: ELISA-array. The ELISA-array assay is based on a \"sandwich\" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use.", "Title: Use of simple clinical and laboratory predictors to differentiate influenza from dengue and other febrile illnesses in the emergency room\nPassage: Among 148 patients diagnosed with dengue infection patients aged \u226418 years), 64 were dengue fever without warning signs, 77 were dengue fever with warning signs, and 7 were severe dengue, based on 2009 WHO case definitions . An individual patient might have received more than one The mean time lapse from onset of symptoms to ER presentation was 3.7 \u00b1 1.8 days, and the mean fever duration was 4.0 \u00b1 2.3 days. The 3 most common symptoms other than fever in dengue patients were malaise , rashes , and joint pain . Marked thrombocytopenia and leukopenia were found in 109 Title: A Combined Syndromic Approach to Examine Viral, Bacterial, and Parasitic Agents among Febrile Patients: A Pilot Study in Kilombero, Tanzania", "Passage: Male enrollment was more common than female enrollment. The median age of enrollment was 23 years . The most common presenting complaints, other than fever, were headache , lethargy , cough , and vomiting . Of all enrolled participants, 116 were admitted for inpatient care and treatment . Patient-level data, inclusive of particular clinical and epidemiologic data as well as diagnostic results, are included in a supplemental file . Title: Use of simple clinical and laboratory predictors to differentiate influenza from dengue and other febrile illnesses in the emergency room", "Passage: Of 526 patients aged \u226418 years) influenza infections, 447 were 2009 pandemic H1N1 and 79 were seasonal H3N2. The mean interval between onset of illness and the patient's arrival at the ER was 1.7 \u00b1 1.2 days, and the mean fever duration was 2.8 \u00b1 1.6 days. Besides fever, the 3 most common symptoms were cough , rhinorrhea , and sore throat . Mild thrombocytopenia was detected in 38 of the 238 patients with an available peripheral platelet count. Of 364 patients receiving oseltamivir, 107 started therapy >48 h after illness onset. The 3 most common influenza-associated complications were pneumonia Title: A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania", "Passage: The most common presenting complaints, other than fever, were headache , cough and abdominal pain . The mean axillary temperature was 38.4\u02daC which was consistent across all age groups. Given similarity in fever distributions among younger children, older children and adults, we could define fever tertiles of all enrolled febrile participants, defined as mild fever , moderate fever , and severe fever . Each tertile comprised approximately 33% of all enrolled participants.", "Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study\nPassage: Information about pre-existing conditions was available for 20 case-patients. Four case-patients had no reported pre-existing conditions or risk factors for severe disease. Pre-existing conditions reported were: morbid obesity/obesity , lung disease , heart disease , pregnancy , diabetes , immunodeficiency , cerebral palsy , prematurity in an infant and genetic disorder . Three case-patients were reported to have more than one pre-existing condition/risk factor. Antiviral therapy was prescribed for 10 case-patients . Antibiotics were prescribed for 10 case-patients . Four case-patients received both antiviral and antibiotic therapy. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Data on pre-existing conditions were reported for seven cases; five had no pre-existing conditions while one was reported to be obese and one had pre-existing cardiac disease. No data on clinical signs e.g. dyspnea etc. were reported for any of the 38 cases. Title: Estimating the number of infections and the impact of non-\nPassage: before testing became widespread. Title: Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008\nPassage: Underlying chronic medical conditions were reported in 11 children, whereby 7 of these had more than Information about the influenza vaccination status was available from 17 patients; none had been vaccinated against influenza. Out of the 11 children from risk groups with chronic underlying disease the vaccination status was not available in 2 patients, and 1 child was < 6 months of age and therefore too young to be immunized.", "Title: Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine\nPassage: Respiratory viral infections, caused by influenza virus, respiratory syncytial virus , human parainfluenza viruses , and coronaviruses, remain a global public health concern . WHO has acknowledged the magnitude of this problem and has highlighted the need for research focused on the prevention of respiratory viral infections. However, except for influenza virus, there are no authorized vaccines available for the prevention of emerging/re-emerging respiratory viral infections . Vaccination is based on the adaptive immune responses that provide protection against a specific pathogen. Safe and controlled activation of the immune system results in a specific memory in the vaccinated hosts and Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: Ongoing studies could identify effective candidates. An active instrument against infection is needed since RSV infection can cause serious complications in infants, young children and the elderly. Title: Vaccination against Paediatric Respiratory Pathogens\nPassage: ARIs are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review focuses on the most recent data about vaccines against respiratory pathogens. The use of influenza, pneumococcal, pertussis and measles vaccines is essential to reduce ARIs burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of RSV virus biology and immunology as well as the development of new techniques to generate vaccine Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: Despite a consensus on the need for an RSV vaccine, there is no licensed product available yet, mainly due to the early age of infection, the capacity of RSV to evade innate immunity, and the failure of RSV-induced adaptive immunity to prevent re-infection . Several clinical trials are now ongoing to assess the safety and effectiveness of different RSV vaccine candidates . Owing to the substantial burden of RSV disease worldwide, RSV vaccine continues to be a necessity for most infants, children and also the elderly. The ideal vaccine should produce long-lasting immunity characterized by a robust Th1-mediated response and", "Title: Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses\nPassage: due to lack of a translatable research model . Title: Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses", "Passage: glands was variable, the number of mother ferrets was always three ferrets per time point. Feces from infant ferrets were collected at the time of anal temperature collection. Each feces was placed directly in RLT buffer or placed directly at -80\u00b0C from the animals' anus to avoid surface contamination. Samples were stored in -80\u00b0C before processing for viral loads or RNA. Samples for RNA were either placed in RNA later or homogenized in TRIzol . Sample aliquots for histopathology were stored in formalin until processing. Title: Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses", "Passage: As the mothers of inoculated infants began to display clinical signs of influenza including temperature increases, weight loss, and mortality, we went on to analyze the upper and lower respiratory tracts of the infants and their mothers to determine virus transmission and pathogenesis. Viral burden in infant NW was first detected Day 1 post-infant-inoculation . The NW of nursing-mothers were positive for influenza virus Day 3 post-infant-inoculation. Viral titers remained high in mother NW Day 6-7 at more than 6 TCID 50 /ml . Residual virus persisted in the mothers' NW by Day 10 . Virus transmission between adult ferrets Title: Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses", "Passage: We next determined if transmission of the virus from infants to mother led to lower respiratory tract infection. Examination of viral titers in the lower respiratory tract of the mothers found virus levels above 6 TCID 50 /ml in both the trachea and lungs post-infant-inoculation in 2 out of 3 mothers investigated . H&E staining of mother lungs revealed delayed, airway-localized inflammation . Day 3/4 post-infant-inoculation, mother lungs showed areas of minimal infiltrating leukocytes . Increased leukocyte infiltration was observed Day 7 post-infant-inoculation where sites of inflammation were dense in mononuclear cells with lymphocyte-like morphology. Infected mother lungs were compared", "Title: Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia\nPassage: Annual immunization is the most important preventive measure . However, two classes of antiviral drugs are available and play an important role in the treatment and prevention of influenza : the neuraminidase inhibitors , oseltamivir and zanamivir, which are active against both influenza A and B viruses; and the M2 inhibitors, amantadine and rimantadine, which are active against all influenza A strains, but have no activity against influenza B viruses. In general, the duration for therapy with an NI is 5 days, and with the M2 inhibitors is three to 5 days. Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: A number of monoclonal and polyclonal antibodies, targeted against a variety of influenza viral proteins, are also in development . Similarly, convalescent plasma has shown potential benefit in the treatment of severe influenza, and further trials are underway . Another area of intense interest is the modification of the host antiviral response to influenza virus infection. There are ongoing preclinical and clinical studies of a variety of other immunomodulatory agents for treatment of influenza, including celecoxib , statins, etanercept, pioglitazone, azithromycin , and interferons . Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Treatment of severe influenza presents multiple challenges. The mainstay of therapy for patients with influenza is initiation of antiviral medication as soon as possible after illness onset . Currently available FDAapproved antiviral medications include neuraminidase inhibitors ; cap-dependent endonuclease inhibitor ; and adamantanes . NAIs and baloxavir have activity against both influenza A and B viruses. Adamantanes only have activity against influenza A viruses and are not recommended for treatment of influenza due to widespread resistance among currently circulating strains of seasonal influenza A viruses. Notably, FDA-approved antiviral medications for treatment of influenza are approved for early treatment of uncomplicated Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Although neuraminidase inhibitors are currently recommended for antiviral treatment of influenza in hospitalized patients based on observational studies, including in critically ill patients, there are a number of novel strategies and products for treating influenza in various stages of development. One approach under investigation is triple-combination antiviral drug therapy, which combines amantadine, ribavirin, and oseltamivir for treatment of influenza in critically ill and high-risk patients. Unfortunately, studies to date have not shown a benefit of TCAD over oseltamivir monotherapy . Several novel antiviral compounds are in various stages of investigation, including small-molecule polymerase inhibitors such as pimodivir and favipiravir .", "Title: The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada\nPassage: Influenza vaccination is the primary strategy to prevent influenza-related morbidity and mortality, especially for older adults, who are at higher risk of severe outcomes . In this age group, influenza vaccines are 24-63% effective in preventing laboratory-confirmed influenza . Due to frequent changes in circulating virus strains, annual vaccination is recommended. Title: The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada", "Passage: It remains unclear whether true vaccine interference is occurring from repeated vaccination or whether the differences between studies are an artefact of residual confounding . Individuals may be more inclined to be vaccinated for the first time if they were infected by influenza in the prior season. Vaccine responses may be enhanced with recent prior infection , such that those who were vaccinated repeatedly may appear to have lower VE. However, measuring immunity arising from previous infection is challenging . In addition, while pooling of multiple seasons can increase statistical power, it can mask important variation at the individual season Title: CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice", "Passage: Influenza A virus is a seasonal virus which affects 32,000 individuals in the US and 600,000 worldwide each year . Those at most risk from complications include young children, pregnant women, asthma sufferers, immune compromised individuals and the elderly. The elderly account for up to 80% of hospitalisations and 95% of influenza associated mortality . To help reduce these severe outcomes, public health authorities recommend that individuals over 65 should receive yearly influenza vaccination. However, several clinical trials and cohort studies have reported low rates of vaccine efficacy in the elderly, as judged by statistically significant reductions in influenza associated Title: The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada", "Passage: However, the impact of repeated vaccination on vaccine effectiveness is uncertain. A randomised trial conducted in the 1970s at a British boarding school found higher influenza incidence among students who had received multiple previous vaccines than among those who received only the current season's vaccine . Results from a larger RCT among adults in the 1980s did not lead to the same conclusion . Based on the antigenic distance hypothesis put forth by Smith et al., negative or positive interference can result from prior season vaccination depending on differences in the antigenic distances between prior and current vaccine strains and", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: an anti-IgE antibody elicited antibodies that bound purified IgE molecules , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. For example, immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes . Phage displaying or chemically Rubinchik and Chow conjugated to sperm antigen peptides or peptide mimics and gonadotropin-releasing hormone are also in development. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: an anti-IgE antibody elicited antibodies that bound purified IgE molecules , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. For example, immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes . Phage displaying or chemically Rubinchik and Chow conjugated to sperm antigen peptides or peptide mimics and gonadotropin-releasing hormone are also in development. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination . The phage particle is immunogenic without adjuvant in all species tested to date, including mice , rats , rabbits , guinea pigs , fish , non-human primates , and humans . Various routes of immunization have been employed, including oral administration as well as subcutaneous , intraperitoneal , intramuscular , intravenous , and intradermal injection ; no published study has directly Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination . The phage particle is immunogenic without adjuvant in all species tested to date, including mice , rats , rabbits , guinea pigs , fish , non-human primates , and humans . Various routes of immunization have been employed, including oral administration as well as subcutaneous , intraperitoneal , intramuscular , intravenous , and intradermal injection ; no published study has directly", "Title: Primate-to-Human Retroviral Transmission in Asia\nPassage: The recent SARS epidemic vividly demonstrates how the economic infrastructure and dense population of Asia facilitate the rapid international spread of disease. The combination of large primate reservoirs, prevalent humanprimate contact, a growing immunocompromised population, and advanced infrastructure in Asia increases the likelihood of a primateborne zoonosis emerging on this continent. Title: Primate-to-Human Retroviral Transmission in Asia\nPassage: than any other context. Title: Primate-to-Human Retroviral Transmission in Asia\nPassage: mucosal splashes with saliva from primates are likely mechanisms of transmission . Title: Transmission Potential of Chikungunya Virus and Control Measures: The Case of Italy", "Passage: the generation interval probability distribution function and the number of gonotrophic cycles of the mosquito. This method can not be applied in our study, as the undertaken control measures have contributed to alter the gonotrophic cycles of the mosquito in a indeterminable manner. We found that the probability of observing a major outbreak after the introduction of an index case depends on the ratio of mosquitoes to humans and was estimated to be in the range of 32%-76%. These results confirm the high risk to Europe of tropical vector-borne diseases as a consequence of globalization, which has been modifying the", "Title: CDC Summary 21 MAR 2020,\nPassage: Highlights of CDC\u2019s Response Title: CDC Summary 21 MAR 2020,\nPassage: Risk of exposure: Title: CDC Summary 21 MAR 2020,\nPassage: Updated March 21, 2020 Title: CDC Summary 21 MAR 2020,\nPassage: COVID-19 Pandemic", "Title: Genetic diversity of swine influenza viruses isolated from pigs during 2000 to 2005 in Thailand\nPassage: estimation years. All of the sequences belonging to one particular lineage for each segment were used for regression analysis. Title: Genetic diversity of swine influenza viruses isolated from pigs during 2000 to 2005 in Thailand\nPassage: The H3 Hb Thai isolates were estimated to have derived from a hypothetical common ancestor in 1976, which had acquired an H3 HA gene from a human-like H3N2 swine strain circulating in the early 1970s. Similar evolutional pattern was observed in the N2 tree . N2 gene of the H1N2 isolate, Sara13021, which HA gene was of classical swine origin, also belonged to the cluster Hb. The branch points of common ancestors for those clusters of N2 genes were estimated to be 1998 for Ha and 1976 for Hb respectively. Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study", "Passage: N2 viruses had circulated the previous years some degree of herd immunity against the new strain was expected. The H1N2 viruses were not associated with severe influenza illness that season. In 2002, a new lineage A/Fujian/411/02-like emerged in Asia and caused significant outbreaks on every continent . Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus\nPassage: The current outbreak of swine infl uenza that originated in Mexico in March 2009 has spread to more than 80 countries causing more than 3,99,232 laboratory confi rmed cases of pandemic infl uenza H1N1 globally and over 4735 deaths reported to World Health Organization as of 11 October 2009 . The WHO declared pandemic alert stage 6 on 11 June 2009, indicating an ongoing infl uenza pandemic . The 2009 swine fl u virus designated H1N1 A/swine/California/04/2009 is not zoonotic swine fl u and is not transmitted from pigs to humans, but rather from person to person and has higher", "Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data\nPassage: Compared to the original search volume, which used 21 cities without sampling, the revised index represents the output of the combination of cities with the high-quality search volume and valuable information obtained from historical cases. Thus, the revised index can predict HFMD cases more reliably. Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data", "Passage: In order to analyze the spatial distributions of different types of keywords across the province, the total search volume for each type of keyword was first determined at the city level. The results show that the search volumes of each type of keyword have a similar spatial distribution across the entire province. Cities suffering from more HFMD cases had a higher search volume for all types of keywords , while cities showing fewer HFMD cases had a lower search volume for all types of keywords. General keywords had a much higher search volume than keywords related to treatment and prevention. Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data", "Passage: was found to be 0.8, but 10 cities showed a correlation of close to or larger than 0.8. When these cities were selected as sample cities to estimate the total search volume for the entire province via B-SHADE, the correlation improved from 0.8 to 0.864. Thus, the revised search volume was found to be more similar to the real cases. Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data\nPassage: revised search volume to examine the predictive effects of the revised search volume.", "Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats\nPassage: Historical reviews Brown et al., 2008a; Jones et al., 2008) of emerging infectious disease events have shown that most are of zoonotic origin, among zoonotic EID events, most originated in wildlife and an estimated 10-40 new human viruses are expected to emerge by 2020. Jones et al. found that 'Wildlife host species richness is a significant predictor for the emergence of zoonotic EIDs with a wildlife origin'. When plotted on a global map, the areas at greatest risk for zoonotic pathogen emergence were the equatorial tropics. These investigators and others suggest that surveillance efforts can be rationally focused both geographically Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats", "Passage: Historical reviews Brown et al., 2008a; Jones et al., 2008) of emerging infectious disease events have shown that most are of zoonotic origin, among zoonotic EID events, most originated in wildlife and an estimated 10-40 new human viruses are expected to emerge by 2020. Jones et al. found that 'Wildlife host species richness is a significant predictor for the emergence of zoonotic EIDs with a wildlife origin'. When plotted on a global map, the areas at greatest risk for zoonotic pathogen emergence were the equatorial tropics. These investigators and others suggest that surveillance efforts can be rationally focused both geographically Title: Disease ecology and the global emergence of zoonotic pathogens", "Passage: It follows that for intervention to be globally effective, in addition to rebuilding public health infrastructure based on the comprehensive view of infectious disease ecology presented here, at least three elements are required: Title: Emerging zoonotic diseases: An opportunity to apply the concepts of nidality and one-medicine\nPassage: There is an overall lack of knowledge regarding the natural history and ecology of these zoonotic organisms . There is an abysmal lack of understanding among the general public and media of the natural occurrence of many biological organisms in the agricultural and animal industry setting as well as in free-ranging animal populations. The natural history, normal ecology, and epidemiology of potential agents of bioterrorism provide scenarios for explaining risk to the human population at large. Understanding the natural history of these organisms and their role in agriculture and free-ranging animal populations provides a context for health care providers to", "Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: setting activity and study objectives. Title: A Simulation Optimization Approach to Epidemic Forecasting\nPassage: study comparing the effects of different objective functions would be beneficial. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity . Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: The emergence of a significant respiratory illness linked to a novel coronavirus represents a test of the global capacity to detect and mange emerging disease threats. Its emergence in China adds an additional dimension in the light of previous experience with SARS. The timing of the outbreak immediately before the Chinese Lunar New Year with its attendant population movements adds extra risk and urgency to the response.", "Title: Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1\nPassage: Eleven CEACAM1 splice variants have been reported in humans 20 . CEACAM1 isoforms can differ in the number of immunoglobulin-like domains present, in the presence or absence of a transmembrane domain and/or the length of their cytoplasmic tail . The full-length human CEACAM1 protein consists of four extracellular domains domain and three immunoglobulin constant region 2-like domains), a transmembrane domain, and a long cytoplasmic tail. The long cytoplasmic tail contains two immunoreceptor tyrosine-based inhibitory motifs that are absent in the short form 20 . The most common isoforms expressed by human immune cells are CEACAM1-4L and CEACAM1-3L 21 . CEACAM1 Title: Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1", "Passage: Eleven CEACAM1 splice variants have been reported in humans 20 . CEACAM1 isoforms can differ in the number of immunoglobulin-like domains present, in the presence or absence of a transmembrane domain and/or the length of their cytoplasmic tail . The full-length human CEACAM1 protein consists of four extracellular domains domain and three immunoglobulin constant region 2-like domains), a transmembrane domain, and a long cytoplasmic tail. The long cytoplasmic tail contains two immunoreceptor tyrosine-based inhibitory motifs that are absent in the short form 20 . The most common isoforms expressed by human immune cells are CEACAM1-4L and CEACAM1-3L 21 . CEACAM1 Title: Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog", "Passage: and 4. The cloned CEACAM25 splice variants also code for proteins with only one N domain followed by a transmembrane domain. Three out of four clones encode cytoplasmic domains which contain the predicted ITAM motif . In one clone, the absence of the 53 nucleotide cytoplasmic domain exon 1 leads to a frame shift and the usage of an alternative stop codon located in cytoplasmic domain exon3 . Using supposedly CEACAM28specific primers, two products were amplified which differ in their length by 276 bp. Cloning and sequencing revealed that the CEACAM28 gene codes for a protein with one N domain, Title: The Transmembrane Domain of CEACAM1-4S Is a Determinant of Anchorage Independent Growth and Tumorigenicity", "Passage: CEACAM1 is a member of the carcinoembryonic antigen gene family of Ig-like cell-cell adhesion molecules . Like other members of this family, CEACAM1 is a type I transmembrane protein with a heavily glycosylated extracellular region composed of four Ig-like domains, a transmembrane domain and a cytoplasmic tail . In the rat liver there are two allelic variants of CEACAM1 which differ by 16 amino acids in their N-terminal domains and two major splice variants, designated 4L and 4S, that are distinguished by differences in the length of their cytoplasmic tails of 70-72 amino acids and 10-12 amino acids, respectively .", "Title: Viral vector-based influenza vaccines\nPassage: testing rAd5 vectors expressing the HA genes from avian viruses of the A, A and A subtype 199, 206 combinations thereof) showed that mice could be protected from homologous challenge infection. Heterosubtypic immunite was never observed, however it was shown that simultaneous vaccination with 5 different rAd5-HA vaccines was feasible and protected from challenge infection with viruses of all subtypes under investigation. 207 Comparable to expressing modified influenza antigens in other vectors with the goal of inducing universal influenza immunity , a rAd expressing a modified HA gene was constructed. This HA gene was modified to shield the immunodominant head Title: Virus-Vectored Influenza Virus Vaccines", "Passage: mice with this construct induced robust neutralizing antibody responses and protected mice from challenge with a heterologous virus, A/Hong Kong/1/1968 . Replication defective rAd5 vaccines expressing influenza HA have also been tested in humans. A rAd5-HA expressing the HA from A/Puerto Rico/8/1934 was delivered to humans epicutaneously or intranasally and assayed for safety and immunogenicity. The vaccine was well tolerated and induced seroconversion with the intranasal administration had a higher conversion rate and higher geometric meant HI titers . While clinical trials with rAd vectors have overall been successful, demonstrating safety and some level of efficacy, rAd5 as a vector Title: An in vivo system for directed experimental evolution of rabbit haemorrhagic disease virus", "Passage: RHDV serum diluted 1/5,000 in standard carbonate buffer. After incubation at 37\u02daC for 1 hour, plates were washed and incubated with a mixture of the mabs 1H3, 5D11 and 2B4 at 37\u02daC for 1 hour. Finally, horseradish peroxidase-labelled rabbit anti-mouse IgG was used to detect the binding of the mabs to the virus. For each virus, the OD 492 value obtained with the non-binding mab 5F5 was set as 0% inhibition. RHDV Bs89 was used as the reference strain for the mabs 2B4, 2G3, 1H8, 2A10 and 1H3, while the antigenic variant RHDVa Pv97 was the reference strain for the Title: A Single Residue Substitution in the Receptor-Binding Domain of H5N1 Hemagglutinin Is Critical for Packaging into Pseudotyped Lentiviral Particles", "Passage: 293T cells transfected with H5 HA were detached with and resuspended in PBS, blocked in 10% horse serum and then labelled with a polyclonal rabbit anti-H5N1 antibody at a 1:400 dilution for 1 hr at 4uC. Unbound antibodies were removed by washing three times with cold PBS, followed by staining with a phycoerythrin -conjugated, donkey-anti-goat secondary antibody for 30 min at 4uC. Data were collected from at least 5000 cells on an LSRII flow cytometer and post-acquisition analyses of cell surface expression of H5-HA was performed using FlowJo software .", "Title: Consequences of delays and imperfect implementation of isolation in epidemic control\nPassage: Roughly 400 infectious diseases have been identified since 1940. New pathogens are emerging at higher rates, despite the increase in awareness and vigilance. A grave public health concern is when and how the next outbreak will occur 1 ; threats of imminent global outbreaks are real 2 . The 1917 Spanish influenza, which killed 50 million people, was the worst-ever pandemic on record -and that was back at a time when travel by ship was the fastest means of transportation around the globe. In today's tightly connected world, an epidemic can potentially travel at jet-speed. Indeed, Swine flu was first Title: European Monitoring Systems and Data for Assessing Environmental and Climate Impacts on Human Infectious Diseases", "Passage: outbreaks has already been examined . Both heavy rainfall and periods of sustained low rainfall appear to be associated with outbreaks. Similarly, cholera outbreaks have been analysed to examine global differences in seasonality . Title: Merging Economics and Epidemiology to Improve the Prediction and Management of Infectious Disease", "Passage: Bovine Spongiform Encephalopathy, Bluetongue or Foot and Mouth disease , and diseases of wildlife-potentially white-nose syndrome in bats . In the USA, many other wildlife diseases and zoonoses have been linked to live animal imports . Trade and travel affect the likelihood that pathogens are spread internationally by altering the number and variety of infectious-susceptible contacts Jones et al. 2008; Suhrcke et al. 2011; Daszak 2012; Kilpatrick and Randolph 2012) . In the same way, the decisions people make to engage with others in their own community affect the spread of disease nationally. Since people take account of potential disease Title: Exposure science in an age of rapidly changing climate: challenges and opportunities", "Passage: will have an increasingly important role as a driver of changes in the ecology of these diseases, influencing both disease incidence and distribution. Severe storms, heat waves, and weather patterns have been linked to outbreaks of many environmentally-sensitive infectious diseases. West Nile Virus transmission intensity has been associated with warmer than normal summer temperatures. 48 Rift Valley Fever outbreaks in East Africa have been correlated with ENSO events. 49 Plague transmission in the Southwest and Rocky Mountain region has been linked to temperature and rainfall patterns leading to increases in wild rodent populations. 50 Waterborne disease outbreaks have been associated", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Respiratory viruses primarily infect and replicate within airway epithelial cells . During the replication process, the cells release antiviral factors and cytokines that alter local airway inflammation and airway niche . In a healthy airway, the inflammation normally leads to type 1 inflammatory responses consisting of activation of an antiviral state and infiltration of antiviral effector cells. This eventually results in the resolution of the inflammatory response and clearance of the viral infection . However, in a chronically inflamed airway, the responses against the virus may be impaired or aberrant, causing sustained inflammation and erroneous infiltration, resulting in the exacerbation Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: eosinophilic infiltration in the asthmatic airway. The effect is also further compounded by the participation of Th1 and ILC1 cells in the COPD airway; and Th2 and ILC2 cells in the asthmatic airway.", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: As at 09:00 on 21 February, few COVID-19 cases had been detected in Europe compared with Asia. However the situation is rapidly developing, with a large outbreak recently identified in northern Italy, with transmission in several municipalities and at least two deaths . As at 5 March 2020, there are 4,250 cases including 113 deaths reported among 38 countries in the WHO European region . Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: As at 09:00 on 21 February 2020, 47 confirmed cases of COVID-19 were reported in the WHO European Region and one of these cases had died . Data on 38 of these cases are included in this analysis. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Date: 2020-03-05 Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068164/", "Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: Nasal swabs were collected from the subjects and stored in DNA/RNA shield . Collected samples were spinned and the swab removed. Residues containing the nasal samples were stored at -20 \u00b0C prior to molecular analysis. Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: We also compared and contrasted the clinical and community results. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses found in the clinical sample. These three infections resulted in 41 viruses detected in 15 subjects clinically, and eight infections detected in five people in the community. Together they infected 94% of clinical subjects, and 7% in the community . The most common virus detected in community samples was Coronavirus OC43; this virus was detected in 13.3% people in the community and not in any of the clinical samples. However a different strain, coronavirus OC 229 Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Abstract: OBJECTIVE: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical surveillance in Nigeria. RESULTS: Children were selected via convenience sampling from communities and a tertiary care center during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority of subjects were under 6 years old, of whom 46 were infected . A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% of clinical subjects, and 6.7% of community subjects . Coronavirus OC43 was the most common virus detected in community members . A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of", "Title: In Vitro Viability and Cytotoxicity Testing and Same-Well Multi-Parametric Combinations for High Throughput Screening\nPassage: cytotoxicity caused by the test compound . Viability and cytotox-icity data can therefore help reconcile aberrant data points or explain decreases in genetic reporter signals due to cell death. Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs\nPassage: Cytotoxicity in mock infected cell plates was measured 48 or 72 h after treatment with compounds using the CellTiter Glo luminescent cell viability assay kit according to the manufacturer's instructions . Luminescence was read on the Infinite 1 M1000 Tecan plate reader . Title: In Vitro Viability and Cytotoxicity Testing and Same-Well Multi-Parametric Combinations for High Throughput Screening", "Passage: A host of new assays have been described and utilized which measure biomarkers of cellular stress or specific signaling events more proximal to initial cytotoxic insult . These methods offer early indication of potential cytotoxicity, but are typically relegated to secondary screening because they are more difficult to employ as endpoint assays due to the transient nature of the biomarker and kinetic differences associated with cell death progression . Therefore assay chemistries predicated upon the detection of changes in membrane integrity remain the gold standard for in vitro cytotoxicity testing. Title: In Vitro Viability and Cytotoxicity Testing and Same-Well Multi-Parametric Combinations for High Throughput Screening", "Passage: Depending upon the goals of the screen, either viability or true cytotoxicity assay chemistries can be employed. Cytotoxicity assays based on membrane integrity changes are positive-readout assays most typically indicated for shorterterm exposure models . These assays may not always accurately estimate the absolute degree of early or late stage cytotoxicity due to the kinetics of biomarker emergence or degradation. Viability assays measure the level of biomarker activity inversely correlated with cytotoxicity and therefore may be used at any endpoint during a compound/cell incubation period.", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Notwithstanding this progress, there remains a disproportionate burden of disease in low-and middle-income countries, where more than 90% of pneumonia cases and deaths occur. The incidence in high-income countries is estimated at 0.015 episodes per child year, compared to 0.22 episodes per child year in low-and middle-income countries . On average, 1 in 66 children in high-income countries is affected by pneumonia per year, compared to 1 in 5 children in low-and middle-income countries. Even within low-and middleincome countries there are regional inequities and challenges with access to health care services: up to 81% of severe pneumonia deaths occur outside Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: a hospital . In addition to a higher incidence of pneumonia, the case fatality rate is estimated to be almost 10-fold higher in low-and middle-income countries as compared to high-income countries . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: odds of severe pneumonia by 2.7 times in low-and middle-income countries and 1.3 times in highincome countries. Markers of undernutrition are strong risk factors for pneumonia in low-and middle-income countries only, with highly significant odds ratios for underweight for age , stunting and wasting . Household crowding has uniform risk, with odds ratios between 1.9 and 2.3 in both low-and middle-income countries and high-income countries. Indoor air pollution from use of solid or biomass fuels increases odds of pneumonia by 1.6 times; lack of measles vaccination by the end of the first year of age increases odds of pneumonia by Title: Economic burden of pneumococcal infections in children under 5 years of age", "Passage: that the mortality rate was 119 per 100,000 and the case-fatality rate was 5% for pneumococcal pneumonia; however, for pneumococcal meningitis, the case-fatality rate was as high as 59% despite the mortality rate of 10 per 100,000. Within the European region identified by WHO, the mortality rate was 25 per 100,000 and the case-fatality rate was 5% for pneumococcal pneumonia, whereas these rates were 3 per 100,000 and 38% , respectively, for pneumococcal meningitis. The differences in quality and accessibility of healthcare services may create differences between countries.", "Title: The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy\nPassage: CHC was classically treated with recombinant PEG-IFNalpha in combination with Ribavirin . The treatment duration was long and wearing, with PEG-IFN-alpha being administered 3 times a week, severe side effects occurring frequently, and still only approximately half of the patients being cured. Since 2014 HCV therapy improved drastically, as several direct acting antivirals targeting HCV NS3/4A protease, NS5A, or NS5B RNA-polymerase were approved. These inhibitors, either alone or in combination with RBV, now heal over 90% of patients treated. Direct acting antivirals are more effective than PEG-IFN-alpha in eliminating HCV, but also treatment duration is shorter , they can be Title: Advanced Molecular Surveillance of Hepatitis C Virus", "Passage: The arrival of the second generation of direct-acting antivirals in 2011 resulted in improved SVR and a revolution in the field of anti-HCV therapy. Despite the development of drug resistance, the initial NS3-4A protease inhibitors telaprevir and boceprevir undoubtedly possessed advantages over dual IFN/RBV treatment . The success of both drugs was subsequently eclipsed by the licensing of simeprevir and sofosbuvir . The field of HCV therapy is rapidly evolving, and as a result, a large number of new antiviral drugs are currently being evaluated in advanced clinical trials . Title: Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus", "Passage: There are approximately 71 million people globally who are chronically infected with hepatitis C virus . A significant number of those with chronic infection will develop cirrhosis, hepatocellular carcinoma or liver failure, resulting in approximately 400,000 deaths each year . Recently approved combination regimens of DAAs, such as sofosbuvir plus ledipasvir or velpatasvir and glecaprevir plus pibrentasvir, have not only drastically improved efficacy outcomes, but have decreased treatment side effects compared to the interferon-containing regimens of the past . Indeed, these regimens have produced sustained virologic response rates greater than 90%, and with treatment duration of 8-12 weeks, depending on Title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection", "Passage: Hepatitis C virus is a positive-stranded RNA virus in the family Flaviviridae, and it is estimated 130-170 million people are infected with HCV worldwide . Acute HCV infection is spontaneously cured in 20%-30% of patients, but the majority of infected patients fail to clear the virus and develop chronic persistent infection . In addition to a combination regimen of pegylated interferon -\u03b1 and ribavirin, direct acting antiviral drugs against HCV have been developed, and a high rate of sustained virological response has been achieved by using these antiviral drugs . However, the high cost of these drugs results in limited", "Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus\nPassage: It has been shown that upon interacting with its receptor, CD40, CD40L induces profound effects on T cells, DCs, B cells, endothelial cells, as well as many cells of the hematopoietic and non-hematopoietic systems. Moreover, when CD40L engages CD40 on the surface of DCs, it promotes cytokine production, the induction of cell surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells , enabling DCs to mature and effectively induce the activation and differentiation of T cells. When CD40L engages CD40 on the surface of B cells, it promotes germinal center formation, immunoglobulin isotype switching, somatic hypermutation to Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: It has been shown that upon interacting with its receptor, CD40, CD40L induces profound effects on T cells, DCs, B cells, endothelial cells, as well as many cells of the hematopoietic and non-hematopoietic systems. Moreover, when CD40L engages CD40 on the surface of DCs, it promotes cytokine production, the induction of cell surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells , enabling DCs to mature and effectively induce the activation and differentiation of T cells. When CD40L engages CD40 on the surface of B cells, it promotes germinal center formation, immunoglobulin isotype switching, somatic hypermutation to Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: enhance antigen affinity, and lastly, the formation of long-lived plasma cells and memory B cells .Various studies have been conducted to utilize gene delivery of CD40L to DCs and tumor cells for tumor immunotherapy. It was found that expression of CD40L in a small proportion of tumor cells was sufficient to generate a long-lasting systemic anti-tumor immune response in mice that was shown to be dependent on cytotoxic T lymphocytes . Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus\nPassage: enhance antigen affinity, and lastly, the formation of long-lived plasma cells and memory B cells .Various studies have been conducted to utilize gene delivery of CD40L to DCs and tumor cells for tumor immunotherapy. It was found that expression of CD40L in a small proportion of tumor cells was sufficient to generate a long-lasting systemic anti-tumor immune response in mice that was shown to be dependent on cytotoxic T lymphocytes .", "Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic\nPassage: shedding was low or missed by swab timing. These 7 cases are termed \"pH1N1+ILI. \" Donors with ILI symptoms but negative PCR and no seroconversion are termed \"non-pH1N1 febrile illness. \" Six pH1N1 infections were detected by seroconversion in donors asymptomatic or reporting symptoms milder than ILI. They are termed \"mild/asymptomatic. \" Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: Responses of 153 donors are shown in Figure 1A ; To assess linkage to reduction in symptoms, baseline T-cell results were compared for donors later infected with pH1N1 who had ILI versus those with mild/ asymptomatic infections . There was a trend toward greater T-cell responses in the mild/asymptomatic group, but the difference was not statistically significant. We also compared our 2 small groups of infected donors for IFN-\u03b3 responses to the peptides with which other investigators found T-cell differences: NP pools only rather than total ELISPOT in the case of Hayward et al , and NP, M, PB1 9-mer Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: of a certain human leukocyte antigen -B family react to this peptide, but not all donors. Thus, this marker could not be used alone for screening purposes but perhaps as part of a group of markers. We describe it as an interesting case study and proof-of-concept for this type of testing. ). One hundred thirty-seven donor sera were tested; each circle represents 1 donor. The solid red circles represent values above a 3% threshold considered positive. Open black circles are considered negative. Values <0 reflect more binding to untransfected cells than to transfected cells , which is presumably nonspecific. Title: Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case\u2013control study", "Passage: The patients were separated into two groups depending whether they were positive or negative for influenza A/H1N1, thereby forming the groups, influenza A/H1N1 and ILI, respectively. In both the A/H1N1 and ILI groups, the majority was male , whereas in the AHC group, 61.93% were female. The mean age of the A/H1N1 and ILI groups was <45 years , compared to that of the AHC group, 56.82% of who were 45-64 years of age.", "Title: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey\nPassage: least 17700 deaths worldwide and the Centers for Disease Control and Prevention reported 59 millions infected people in the USA ). Title: Low-Cost HIV-1 Diagnosis and Quantification in Dried Blood Spots by Real Time PCR", "Passage: It is estimated that 33.2 million people were infected with HIV-1 at the end of 2007; 2.5 million were children under 15 years of age, the majority of whom acquired infection through mother-tochild transmission ). Antiretroviral therapy is effective at blocking MTCT and can markedly improve the outcome of pediatric HIV-1 infection. However, efforts to provide widespread access to ART have been hampered by the limited availability of infant diagnostic methods. Methods to diagnose and monitor HIV-1 infection in resource-poor settings are usually limited to serologic assays and CD4/CD8 counts. However, antibody based assays can reliably guide diagnosis and management Title: HIV/AIDS prevention in China: A challenge for the new millennium", "Passage: about 30,000 HIV cases nationwide, although their official count was later revised 25-fold upwards to 840,000. By 2003 the United Nations had estimated that the number of cases was closer to 1.5 million . In the first half of 2001 alone, China's HIV incidence rate increased by 67% , and at least 80,000 people now have full-blown AIDS . The Chinese Academy of Preventive Medicine finally acknowledged in 2001 that they may soon have the largest HIV infected population in the world, possibly 6 million cases by 2005 . With infection rates now rising at about 30% per year, the Title: Worldwide circulation of HSV-2 \u00d7 HSV-1 recombinant strains\nPassage: America, and Africa, with a few from Asia or of unknown origin. Men comprised 38% of the cohort with 50% women and 12% unknown, while 44% were HIV-1 infected, 45% HIV-1 uninfected, and 11% unknown.", "Title: Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017\nPassage: According to the California Code of Regulations, meningitis cases are reportable to the California Department of Public Health within 1 day of identification of etiology . In the fall of 2017, a cluster of aseptic meningitis cases from a northern California high school were reported to the CDPH. The Viral and Rickettsial Disease Laboratory at the CDPH detected EV from 19 of 30 patients by real-time reverse transcription-PCR , as previously described . We generated and analyzed partial capsid ) sequences using methods developed by Minnaar et al. . Fifteen of 19 EV-positive patients were confirmed to have echovirus 30 Title: The combination of decoy receptor 3 and soluble triggering receptor expressed on myeloid cells-1 for the diagnosis of nosocomial bacterial meningitis", "Passage: Diagnosis of bacterial meningitis was based on a positive result of CSF culture. Nosocomial meningitis was defined as negative bacterial infection when the patient was admitted to the hospital, clinical evidence of an infection was found after 48 hours on admission or within one month after discharge from the hospital where the patient had received an invasive neurosurgical procedure. Otherwise, the patient was considered to have community-acquired meningitis . External ventricular drain-related meningitis was diagnosed with bacterial infection being found within 7 days of external ventricular drain removal . Title: Description of two measles outbreaks in the Lazio Region, Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection", "Passage: In Italy, measles is a disease subject to mandatory notification, and according to the routine procedure, physicians must report suspected measles cases to their LHU within 48 hours of diagnosis. The local health authorities then report confirmed measles cases to the ASP monthly. At the beginning of the outbreaks this procedure was modified and physicians were asked to report suspected measles cases to both the local health authorities and ASP offices within 24 hours of diagnosis. Personnel of the LHUs performed epidemiological investigation of suspected cases including laboratory investigation and contact tracing. Title: Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China", "Passage: before the onset of any symptom. The epidemiological investigations were performed through direct contacts in the relevant village, community, or school, or through direct contacts for mass gathering events. The clinically confirmed and laboratory-confirmed cases were both regarded as cases, and reporting personnel were required to report such cases to the NIDMIS within 6 hours.", "Title: Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity\nPassage: transduction, cell differentiation, and development to cell cycle control and metabolism. Enzymes and receptors can be switched \"on\" and \"off \" by phosphorylation and dephosphorylation. It was estimated that 10-50% of proteins are phosphorylated. Phosphorylation often occurs on serine, threonine, and tyrosine residues in eukaryotic proteins . Analysis of the entire cellular phosphoproteome has been an attractive study subject since the discovery of phosphorylation as a key regulatory mechanism of cell life. Unfortunately, phosphoproteins analysis is not straightforward for five main reasons. First, the stoichiometry of phosphorylation is generally relatively low, because only a small fraction of the available intracellular Title: Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics", "Passage: CK2 inhibitors were found to depress GH-induced activation of STAT5, consistent with CK2 playing a role in GH signaling. With kinases like CK2 that are constitutively active, the regulation of ligand-dependent signaling likely requires a change in the conformation of protein substrates or altered subcellular localization of substrates or kinases to permit phosphorylation. Therefore, for potential substrates of CK2, it may be informative to determine whether any GH-dependent changes in subcellular localization of the substrates can be detected. Title: Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics\nPassage: ACLY is the primary enzyme responsible for the synthesis of cytosolic acetyl-coenzyme A in many tissues. Phosphorylation of ACLY Ser455 by Akt has been shown to activate ACLY . Title: Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics", "Passage: To gain insight into the reliability of the identification of the novel GH-dependent phosphosites, we performed immunoblotting with phosphospecific antibodies. Sites with available antibodies included three sites in proteins associated with the mTOR pathway , one site identified in a protein in the insulin and focal adhesion categories , and one site identified in a protein involved in regulation of actin cytoskeleton . Of these, PRAS40 Thr247 and NHE1 Ser707 fell into the category of Akt/PKA substrate sites. We also tested for phosphorylation at two additional Akt/PKA substrate consensus sites, NDRG1 Ser330 and ACLY Ser455. All of these sites were", "Title: Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1\nPassage: spillover . In humans, VEEV causes a febrile illness typified by fever, malaise, and vomiting. In some cases, infection progresses to the central nervous system and neurological symptoms, such as confusion, ataxia, and seizures, manifest. The mortality rate among cases with neurological symptoms can be as high as 35% in children and 10% in adults, with long-term neurological deficits often being seen in survivors . In 1995, an outbreak of VEEV in Colombia and Venezuela resulted in over 100,000 human cases . In addition to natural outbreaks, VEEV is also a concern from a bioterrorism perspective, as it can be Title: Treatment of Neuroterrorism", "Passage: Diseases caused by alphaviruses are mainly neurological and include Venezuelan equine encephalomyelitis and Eastern and Western equine encephalomyelitis. This disease occurs naturally in North, Central, or South America, but human illness is rare, and most infections result in nonspecific symptoms of fever, headache, and myalgia. Less than 6% of infected adults or children will develop encephalitis, however the mortality rate of those can be as high as 50 to 75% for Eastern equine encephalitis , which is the most severe of these infections, and survivors frequently have neurological sequelae . Title: Treatment of Neuroterrorism", "Passage: Venezuelan equine encephalitis virus is an alphavirus that is most commonly found in Central and South America. It is transmitted to humans by mosquitoes. In case of a bioterrorist attack, the distribution would be made through aerosols . The virus usually leads to an initial severe febrile illness in nearly everyone exposed at 1 to 6 days after exposure. Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas\nPassage: within the VEE subtype, subtype II Everglades virus , which is found only in Florida, can cause neurologic disease in humans and equids . Subtype IIIA, Mucambo virus, also causes febrile disease in humans .", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Ninety-five percent of infected adults are symptomatic after infection, and of these, most become disabled for weeks to months as a result of decreased dexterity, loss of mobility, and delayed reaction. Eighteen months after disease onset, 40% of patients are found to still have anti-CHIKV IgM . The chronic stage of CHIKF is characterized by polyarthralgia that can last from weeks to years beyond the acute stage . CHIKV has been shown to attack fibroblasts, explaining the involvement of muscles, joints, and skin connective tissues. The high number of nociceptive nerve endings found within the joints and muscle connective tissues Title: Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses", "Passage: rashes, arthralgia and myalgia. The typical clinical sign of the disease is poly-arthralgia, which is a very painful condition affecting joints and may persist for several months to years in some cases . Being an arthropodborne virus, the mode of transmission is the mosquitoes of the Aedes spp. It is generally accepted that CHIKV originated from Africa, where it is primarily maintained in a yellow fever-like zoonotic sylvatic cycle and depends upon non-human primates and arboreal, peridomestic mosquitoes as reservoir hosts. However, the spread of CHIKV in Asia and urban endemics are associated with a dengue-like ''human-mosquito-human'' direct transmission cycle, Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: Text: Chikungunya virus , a mosquito-borne pathogen listed by National Institute of Allergy and Infectious Diseases as a Category C Priority Pathogen that causes Chikungunya fever , has been spreading throughout Asia, Africa, and parts of Europe in recent times . CHIKV is an arthropod-borne virus and is transmitted to humans primarily by Aedes aegypti, the infamous yellow fever propagator . CHIKV infection is marked by severe joint pain, contorting its victims into unusual postures . The disease gets its name from the Kimakonde vernacular language of Tanzania and Mozambique, and the word chikungunya means ''that which contorts or bends Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: can explain pain associated with CHIKF .", "Title: Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection\nPassage: Endothelial cells create a physical barrier on the luminal surface of blood and lymphatic vessels. This barrier must be traversed by blood-borne pathogens and immune cells trafficking between tissues and the bloodstream. Many herpesviruses require systemic spread for persistence within a host, and therefore must cross such an endothelial cell barrier. To date, herpesviruses have been implicated as potential initiators of arterial injury, endothelial dysfunction, and local inflammation, possibly contributing to the pathogenesis of atherosclerosis . Human cytomegalovirus , a betaherpesvirus, infects endothelial cells in vivo. Studies have shown that infected endothelial cells play a role in HCMV dissemination and Title: Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection", "Passage: Endothelial cells serve as a natural site of infection and possible viral reservoir of HCMV , suggesting a role for HCMVinfected endothelial cells in viral spread and persistence. Additionally, recent reports implicate circulating endothelial progenitor cells as potential reservoirs of KSHV and possible precursors of KS spindle cells . However, the specific mechanisms by which infected endothelial cells contribute to the pathogenesis of these human viruses remains unclear. Murine cHV68 pathogenesis involves dissemination from the lung to lymph nodes, spleen, and peritoneum . In light of this systemic spread, cHV68 likely encounters an endothelial cell barrier. Title: The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract", "Passage: Endothelial cells in the past were considered as collateral damage when the process of DAD was initiated as a loss of the endothelial integrity with subsequent microvascular leakage was a key feature in bacterial sepsis and in viral infection such as H5N1 . In the 2009 pandemic autopsy studies demonstrated viral antigen in endothelial cells and if the same can be demonstrated in H5N1 infection this may explain the extrapulmonary dissemination of virus in these infections . It has also been shown that polarized endothelial cells can be infected in vitro . Intriguingly recent publications have shown that endothelial cells Title: Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection\nPassage: infection.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Text: The prevalence of chronic airway inflammatory disease is increasing worldwide especially in developed nations . This disease is characterized by airway inflammation leading to complications such as coughing, wheezing and shortness of breath. The disease can manifest in both the upper airway and lower airway which greatly affect the patients' quality of life . Treatment and management vary greatly in efficacy due to the complexity and heterogeneity of the disease. This is further complicated by the effect of episodic exacerbations of the disease, defined as worsening of disease symptoms including wheeze, cough, breathlessness and chest tightness . Such exacerbations Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Another recent area of interest is the relationship between asthma and COPD exacerbations and their association with the airway microbiome. The development of chronic airway inflammatory diseases is usually linked to specific bacterial species in the microbiome which may thrive in the inflamed airway environment . In the event of a viral infection such as RV infection, the effect induced by the virus may destabilize the equilibrium of the microbiome present . In addition, viral infection may disrupt biofilm colonies in the upper airway microbiome to be release into the lower airway and worsening the inflammation . Moreover, a viral", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: virus is usually described by the media as 'deadly' and although this is true in the sense that it has caused deaths, the nuances of uncertain case fatality rates in the early stages of an outbreak are not being communicated. The current estimated case fatality rate seems to be around 3% which is significant but not comparable to the 10% rate for SARS or 34% reported for MERS. These misperceptions are still driving public anxiety. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In the only study to examine the effect of sample type on molecular analysis, 64 nasopharyngeal aspirates , 30 tracheal aspirates, 13 sputa and three BAL were examined. The tracheal aspirates and BAL returned the highest viral load values followed by NPA and sputum. Unsurprisingly, higher viral loads generally paralleled whole genome sequencing and culture success and, in NPA testing, were significantly correlated with severe disease and death . This study demonstrated the importance of LRT sampling for whole genome sequencing. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Clinically suspected MERS cases may return negative results by RT-rtPCR. Data have shown one or more negative URT samples may be contradicted by further URT sampling or the use of LRT samples, which is preferred . Higher viral loads occur in the LRT compared to the URT. This fits with the observation that the majority of disease symptoms are reported to manifest as systemic and LRT disease . However, on occasion, even LRT specimens from MERS cases may initially be negative, only to later become positive by RT-PCR . This may be due to poor sampling when a cough is Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: absent or non-productive or because the viral load is low . Despite this both the largest human MERS-CoV studies and smaller ones , use samples from the URT. It is then noteworthy that one study reported an association between higher loads in the URT and worse clinical outcome including intensive care and death . At writing, no human data exist to define whether the virus replicates solely or preferentially in the LRT or URT, or replicates in other human tissues in vivo although MERS-CoV RNA has been detected from both the URT and LRT in a macaque monkey model .The Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms. LRT samples are also best for attempting isolation of infectious virus, although the success of culture is reduced when disease persists . Recommended sample types include bronchoalveolar lavage , tracheal/tracheobronchial aspirate, pleural fluid and sputum . Fresh samples yield better diagnostic results than refrigerated material and if delays in testing of \u226572 h are likely, samples should be frozen at \u221270\u00b0C . If available, lung biopsy or autopsy tissues can also be tested .", "Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines\nPassage: In general, there are several advantages of baculovirus-expressed vaccines, such as baculovirus-expressed virus-like particles and baculovirus surface display, over inactivated vaccines. One advantage of baculovirus-expressed vaccines is the complete elimination of any fear that may arise from the incomplete inactivation of the highly pathogenic viruses during the manufacturing process of inactivated vaccines, which is a concern that inactivated vaccines hold. Such extra peace of mind is attributed to two facts, namely no EV71 virus genomic material is present in baculovirus-expressed vaccines; and baculoviruses are harmless, largely owing to their non-replicable nature in mammalian cells . Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines", "Passage: Baculoviruses are a group of insect-specific pathogens, with each species and/or strain targeting a very limited host range . A particular strain of this virus, namely Baculovirus Autographa californica nuclear polyhedrosis virus , capable of infecting a broad range of lepidopteran hosts, was isolated, and eventually formed the basis for modern day recombinant baculovirus vectors, which are widely used for protein expression . The baculovirus expression system has been widely exploited in modern-day research for protein expression due to its superiority over the traditional expression systems, in particular the E. coli expression system . Such superiority of BVES could be Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines", "Passage: Firstly, live wild-type baculoviruses alone are proven to induce immune responses, both innate and cell-mediated immunity, upon their inoculation into the body . Hence, displaying the antigens on the baculovirus surface and using such recombinant baculoviruses live may reduce the need for adjuvants. Secondly, although baculoviruses are unable to replicate within mammalian host cells, they are capable of transducing them . Lastly, the Ie1 promoter used to regulate the expression of foreign genes in the baculovirus surface display is an active promoter not just in insect cells, but also in mammalian cells . Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus", "Passage: Since its inception more than 30 years ago, the baculovirus expression vector system has been widely used to express heterologous foreign proteins . Autographa californica nucleopolyhedrovirus -Sf9 and Bombyx mori nucleopolyhedrovirus -silkworm are two typical BEVSs . The BmNPV-silkworm offers several advantages in comparison with the AcMNPV-Sf9 system .", "Title: Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus\nPassage: To identify the most-effective rVSV/EBOV vector design for induction of EBOVGP-specific immune responses, the vectors outlined in Figure 1A were compared for their ability to elicit EBOVGP-specific cell-mediated immune and binding antibody responses in mice . Groups of BALB/c mice were immunized intramuscularly at study week 0 . Ten days after primary immunizations, splenocytes were collected from 5 mice/group and tested for EBOVGP-specific IFN-\u03b3 secretion by ELISpot assay. The remaining 5 mice/ group were boosted intramuscularly at study week 3 with 10 7 PFU of each rVSV/EBOV vector. Ten days after boosting, splenocytes were collected and tested as described above. Title: BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1((-/-)) Mice from Monkeypoxvirus Lethal Challenge", "Passage: with B6R alone. Nevertheless, our studies reveal that protection can be afforded even when a small number of mice are used. Further studies should be considered that increase the dose of vector administered to the mice. Also, since the combination of all 3 vectors gave 80% protection against mortality and morbidity, various vector permutations should be considered to elucidate the most efficacious combination and ratio of vectors. Title: Viral vector-based influenza vaccines\nPassage: were capable of inducing protective immunity against infection with homologous viruses in mice. Although recombinant baculovirus vector vaccines were tested in mice, efficacy data in other animal models is still lacking. Short-term production of baculovirus-based influenza virus vaccines for use in clinical trials is therefore not likely. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Baculovirus vectors have been tested as influenza vaccines, with the first reported vaccine using Autographa californica nuclear polyhedrosis virus expressing the HA of PR8 under control of the CAG promoter . Intramuscular, intranasal, intradermal, and intraperitoneal immunization or mice with AcCAG-HA elicited HA-specific antibody responses, however only intranasal immunization provided protection from lethal challenge. Interestingly, intranasal immunization with the wild type AcNPV also resulted in protection from PR8 challenge. The robust innate immune response to the baculovirus provided non-specific protection from subsequent influenza virus infection . While these studies did not demonstrate specific protection, there were antigen-specific immune responses and", "Title: Nanorobot Hardware Architecture for Medical Defense\nPassage: Time for incubation of pandemic syndromes may vary from one contagious plague to another, and first symptoms can be predicted given clinical information and previous historic occurrences, using statistical models. The size of an outbreak is directly correlated and influenced by the delay for recognition about the contaminated area. The incubation period of disease is the time from exposure to the infectious agent to the onset of disease, and depending on the infection dose of influenza, it can vary about 2 to 5 days . For influenza, the contamination can happens through inhalation, ingestion, or direct contact through hand shaking Title: Introducing the Outbreak Threshold in Epidemiology", "Passage: as the fact that the incubation period is around 5 days, by which point it had easily caused more secondary cases. However, in subsequent outbreaks super-spreaders might not be infected early on, allowing more time to contain the spread. Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Astrovirus, rotavirus, and caliciviruses are important causes of healthcare associated infections and institutional outbreaks . The incubation period is important for accurate surveillance for healthcare associated infections and implementation of effective outbreak control measures . The incubation period is frequently used to determine the infecting exposure in foodborne outbreaks and can assist in diagnosis when laboratory resources are unavailable. Kaplan's criteria were developed and are frequently employed to determine whether an outbreak was caused by norovirus; the incubation period is one of the key elements of these criteria. Other applications of a precisely described incubation period include predictive models that Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Despite its importance, the incubation periods of enteric viruses are not well characterized in the medical literature. Statements of the incubation period tend to be a single number ) or a poorly defined range ). It is difficult to translate these statements of incubation period into the realities of prevention and control. The single number estimate could represent the mean, median, upper limit, or some other measure of the incubation period. The range could represent an exhaustive range of all observations, or some unspecified quantile . Furthermore, the strength of the evidence behind these estimates is often unclear. Statements of", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Computed tomography can play a role in both diagnosing and categorizing Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: CT: computed tomography Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Our diagnostic process is limited as chest CT along is not diagnostic of COVID-19 Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: scanning can reduce the radiation damage to patients.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: contrast, the combination therapies led to 50% and 90% survival, depending on the Zanamivir concentration. Statistical analysis showed that the Zanamivir mono-therapy 1 mg/kg BW/day did not show a significant benefit , whereas the mono-therapy with 3 mg/kg BW/day significantly increased the survival rate compared with placebo treated mice . Both Zanamivir concentrations experienced significant benefit in survival by the combination with carrageenan . Similarly, the combination therapies resulted in remarkably increased survival when compared to the carrageenan mono-therapy. No statistically significant difference was observed between the combination containing 3 mg/kg BW/day Zanamivir and that containing 1 mg/kg BW/day . Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Two virus strains were selected for those experiments, one being the most sensitive to carrageenan pdm) and one being the least sensitive . In both cases the isobolograms show a synergistic interaction of carrageenan and Zanamivir . Thus, it was shown that Zanamivir and carrageenan target individual influenza viruses with different efficiencies, most probably due to their different antiviral strategies. As a result, the combination provides synergistic activity with higher protection against a broader spectrum of influenza virus strains than the individual compounds. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: We found that the combination of carrageenan with 3 mg/kg BW/day Zanamivir used for treatment of H7N7 infected mice resulted in significantly enhanced survival of mice in comparison to both mono-therapies . The significantly enhanced survival compared to the placebo treated group was also found after a delayed treatment start 48 hpi. Furthermore, in the H1N1pdm model the combination of carrageenan with 1 mg/kg BW/day Zanamivir showed statistically significant enhanced survival in comparison to placebo treatment even after a treatment start 72 hpi. This is a remarkable finding since NIs are normally not effective when applied 72 hpi. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: virus which has caused more than 175 deaths until October 2014 . Second, they are of special interest for the carrageenan/Zanamivir combination approach. They have shown to differ in in-vitro susceptibility to carrageenan, Zanamivir and the combination thereof . While H1N1pdm was highly sensitive to inhibition by both substances alone, H7N7 required much higher concentrations of carrageenan and Zanamivir, respectively, to achieve similar inhibition efficiencies. Therefore, both virus strains were chosen to further explore the efficiency of the combination therapy in a mouse model.", "Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: Ltd), scheduled for administration at 6, 10, and 14 weeks, is received with significant delays . These data support the WHO's recommendation that countries using whole cell pertussis vaccine continue to do so given that the majority of outbreaks have been concentrated in countries using the acellular pertussis vaccine . Recent studies suggest that protection from acellular pertussis vaccine is not as strong or long lasting as that conferred by the whole cell pertussis vaccine . Title: Neonatal Pertussis, an Under-Recognized Health Burden and Rationale for Maternal Immunization: A Systematic Review of South and South-East Asian Countries", "Passage: In 2011, the Tdap vaccine was recommended in unvaccinated pregnant women by the US Advisory Committee on Immunization Practice . The WHO recommended that national programs consider the vaccination of pregnant women with one dose of Tdap when infant morbidity or mortality from pertussis is high or increasing . Pertussis vaccination practices differ across the Asia-Pacific region, with only some countries recommending booster dosing. Countries usually adapt their recommendations from the WHO based on local information about risk groups, disease burden and cost-effectiveness, but these data are limited in low-or middleincome countries . Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: In conclusion, prevention of pertussis with currently available vaccines reaching high vaccination coverage rates remains a priority, including the vaccination of pregnant women . Several different aP vaccines are available, but it has yet to be determined which of them confers the highest and the most-prolonged protection. Further studies are needed to evaluate the importance of individual antigens included in aP vaccines in conferring protection against disease, colonization, and transmission. However, present knowledge seems to indicate that pertussis toxin, particularly if genetically detoxified, represents the main antigen that ensures protection from disease even if not from infection. The optimal pertussis Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: Pertussis Pertussis cases and deaths were based on a natural history model using vaccine coverage and age-specific case fatality rates from community-based studies . Updated estimates for 2004 were prepared by the WHO Department of Immunization, Vaccines and Biologicals using WHO-United Nations Children's Fund estimates for vaccine coverage in 2004, interpolated for missing data .", "Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus\nPassage: in the mixed nucleolar fraction. Of note, nucleolin was equally distributed between the nuclear and cytoplasmic fractions. This distribution pattern for nucleolin appears to be specific for Jurkat T-cells as show previously . The nuclear protein PARP-1 was present in the nuclear and nucleoplasmic fraction but was depleted in the nucleolar fraction. Alpha-tubulin was highly abundant in the cytoplasmic fraction and weakly detected in the nuclear fractions. Collectively, these results confirmed that our methods produced a highly enriched nucleolar fraction without significant cross contamination. Title: Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription", "Passage: EGFP-TARG1 was reported to be predominantly nuclear 9 , and our proteomics data set contained a high number of nuclear and in particular nucleolar proteins, also reflected by GO analyses for cellular component . Therefore, we analyzed the sub-cellular localization of TARG1 in greater detail. EGFP-TARG1 expressed in U2OS cells accumulated in nucleoli in living cells, while EGFP alone was excluded from nucleoli . mCherry-tagged Histone H2B was used to define the nucleoplasm 28 . Title: Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton", "Passage: Microtubules are polarized filaments formed by tubulins and microtubule-associated proteins. In many eukaryotic cell types, the minus-ends are located near the cell center and plus-ends point to the plasma membrane . In addition to maintaining the structure of the cells and providing the framework for cell division, microtubules serve as tracks for the intracellular transport of organelles, proteins, and RNA-protein complexes . Microtubules support long range virion transport at \u00b5m/s speed. The role of microtubules in virus entry and egress from infected cells has been extensively reviewed . Microtubules are composed of different isotypes of alpha and beta tubulin, which Title: Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells", "Passage: To investigate whether these bortezomib-induced changes in the tubulin polymerization were mediated by phosphorylation of stathmin, we examined the tubulin polymerization in stable U266 clones that overexpressing WT stathmin and the phosphorylation site-deficient stathmin mutants S16A, S25A and S38A. As shown in Figure 5C , by comparing with U266 cells, overexpression of WT stathmin and phosphorylation site-deficient mutants resulted in a significant decrease in the percent of polymerized tubulin following treatment with bortezomib .", "Title: Pandemic Influenza Planning in the United States from a Health Disparities Perspective\nPassage: groups who are vulnerable because of social disadvantage. Nor does it note the need for explicit attention to vulnerable social subgroups, for example, low-wage workers in prioritized occupational fi elds and low-income and minority pregnant women, infants, and toddlers. We are not questioning the rationality of defi ning major priority groups according to occupation or of using biological criteria to further prioritize within the general population. Rather, our concern is with the absence of attention to both biological and social risk factors, which must be addressed to overcome the many social barriers to equal opportunity for vaccination. Title: Pandemic Influenza Planning in the United States from a Health Disparities Perspective", "Passage: On a US government website for pandemic infl uenza , a question asks which groups would be especially vulnerable during an infl uenza pandemic. The answer notes that people may be vulnerable for a variety of reasons, including limited access to healthcare; limited profi ciency in English; or being disabled, homeless, economically disadvantaged, or a single parent. The response calls for faith-based and community-based organizations to develop plans \"to care for dependent populations\" and to \"provide fi nancial aid to the poor who are unable to work and are in need of emergency income for housing, medicine, or other essential Title: Existing health inequalities in India: informing preparedness planning for an influenza pandemic", "Passage: Experience suggests that younger, weaker and politically marginalized sections of society suffer disproportionately in disasters and crises. For example, during the Indian Ocean tsunami of 2004, mortality was higher among females, among those below 15 years of age and among those with no education compared with those with at least 1 year of education . In a cohort study of the population affected by an earthquake in Taiwan in 1999, poor pre-quake mental and physical health status and lower monthly wage were associated with higher risk of mortality . Title: Pandemic Influenza Planning in the United States from a Health Disparities Perspective", "Passage: Crowding, an established risk factor for many infectious diseases, can increase the likelihood of pathogen transmission. In the United States, urban poverty and Hispanic and Asian ethnicity are correlated with domestic crowding; even at higher income levels, Hispanic and Asian households are relatively more crowded than white and African-American households . In addition, in the United States, low-income persons, African Americans, and nonwhite Hispanics are more likely than persons in other groups to obtain regular medical care at emergency departments and publicly funded clinics , where airborne transmission of infectious agents has been documented. Because these locations typically do not", "Title: Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics\nPassage: SILAC was achieved by growing 3T3-F442A preadipocytes in DMEM containing 5% dialyzed fetal bovine serum, 100 U/ml penicillin, 100 g/ml streptomycin, 0.25 g/ml amphotericin, and either Lys and Arg or Lys and Arg for at least seven cell doublings. For the cells grown in Lys and Arg, heavy isotope incorporation was evaluated by running a pilot digestion of the heavy isotope labeled cell extract followed by LC-MSMS analysis. The heavy isotope-labeled amino acids were incorporated into more than 99% of the cellular protein. Cells were washed and incubated in DMEM containing 1% BSA, 100 U/ml penicillin, 100 g/ml streptomycin, 0.25 Title: Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity", "Passage: 18O Stable Isotope Labeling. Differential 16O/18O coding relies on the 18O exchange that takes place at the Cterminal carboxyl group of proteolytic fragments, where two 16O atoms are typically replaced by two 18O atoms by enzyme-catalyzed oxygen exchange in the presence of H218O . The resulting mass shift between differentially labeled peptide ions permits identification, characterization, and quantitation of proteins from which the peptides are proteolytically generated. In contrast to ICAT, 18O labeling does not favor peptides containing certain amino acids , nor does it require an additional affinity step to enrich for these peptides . Unlike iTRAQ, 16O/18O labeling Title: Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target", "Passage: SILAC labeling and preparation of cell extracts. Five biological replicates of the phosphoproteomic experiment were performed using SILAC-labeled A549 cells. For each replicate, two T150 flasks of cells labeled with each of the following conditions were used: L , where A549 cells were grown in normal DMEM; M , where A549 cells were grown in DMEM containing 4,4,5,5-D 4 lysine and 13 C 6 arginine; and H , where A549 cells were grown in DMEM containing 13 C 6 15 N 2 lysine and 13 C 6 15 N 4 arginine. Incorporation of the different isotopes was confirmed by LC-MS/MS. Title: Kinetic Modelling of Infection Tracers [(18)F]FDG, [(68)Ga]Ga-Citrate, [(11)C]Methionine, and [(11)C]Donepezil in a Porcine Osteomyelitis Model", "Passage: Methionine is a naturally occurring essential amino acid. It can be labelled with the positron-emitter 11 C to obtain the chemically identical PET tracer methionine. Methionine is transported into cells via the Ltype amino acid transporter 1. It is crucial for the formation of proteins and is involved in the synthesis of phospholipids. The accumulation of methionine therefore reflects amino acid transport and protein synthesis. During cell replication, the demand for essential amino acids increases, as do protein and phospholipid synthesis. Although primarily used to detect malignant tumours , methionine is known from brain studies to accumulate in inflammatory tissue", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: As at 09:00 on 21 February 2020, 47 confirmed cases of COVID-19 were reported in the WHO European Region and one of these cases had died . Data on 38 of these cases are included in this analysis. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: As at 09:00 on 21 February, few COVID-19 cases had been detected in Europe compared with Asia. However the situation is rapidly developing, with a large outbreak recently identified in northern Italy, with transmission in several municipalities and at least two deaths . As at 5 March 2020, there are 4,250 cases including 113 deaths reported among 38 countries in the WHO European region . Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.", "Title: Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015\nPassage: Breast cancer is the most common type of cancer among women worldwide. It ranks first amongst cancer in Saudi females with an incidence of 19.8 % . Few studies have shown that the knowledge, awareness, and protective measures against this disease are very low in Saudi females . Objective of this study was to assess the level of awareness, knowledge, and practices of breast cancer among Saudi females living in Jeddah. Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: the leading cause in four of the seven regions, second in two regions and fifth in the Western Pacific Region. Stomach cancer is the main cause of cancer death among women in that Region, followed by lung cancer and liver cancer. Cervix uteri cancer is the number one cause of cancer deaths in the South-East Asia Region and the African Region. Other cancers of the female reproductive system are the eighth and thirteenth leading causes of cancer deaths globally. \u2022 acute respiratory infections, mainly pneumonia Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: hepatitis B virus in the case of liver cancer. Globally, lung cancer is the most common cancer , followed by breast cancer, then colon and rectum cancer, and stomach cancer. Lung cancer is also the leading cancer in the Western Pacific Region, but is less common than colon and rectum cancers or breast cancers in most other regions. Cervix cancer is the cancer with the highest incidence in the African and South-East Asia regions, even though it occurs only in women. Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: is the second leading cause of cancer death in the African Region. Colon and rectum cancers are the fourth leading cause and oesophagus cancer the fifth leading cause globally. Prostate cancer is sixth globally, but is the leading cause of cancer deaths in the African Region and in the low-and middle-income countries of the Region of the Americas. In the South-East Asia Region, For women, 15 cancers are ranked for each of the regions. The most common cancer at the global level is breast cancer, followed by cancers of the trachea, bronchus and lung, and stomach cancer. Breast cancer is", "Title: Tuberculosis mortality: patient characteristics and causes\nPassage: on chest radiograph, and were treated as having bacterial pneumonia; 4) they were often older patients with underlying comorbidity and a high risk of developing adverse drug effects, so physicians may not start empirical anti-TB treatment even when TB is highly suspected. Title: Identification of antigens presented by MHC for vaccines against tuberculosis", "Passage: Mycobacterium tuberculosis , the etiologic agent of tuberculosis is the largest cause of death by an infectious disease worldwide. M. africanum, M. canettii, M. microtti, and M. bovis, share 99.9% similarity at the nucleotide level and are grouped in the Mycobacterium tuberculosis complex , the mycobacteria causing TB disease. According to the last World Health Organization report, 1.6 million people died of TB, 300,000 of which were co-infected with HIV, in 2017 1 With the emergence of multi-drug and extensively-drug resistant strains, as well as co-infection with HIV, new tools to control this epidemic are urgently required. The currently available Title: Tuberculosis mortality: patient characteristics and causes", "Passage: All of the authors declare no financial, professional, or otherwise personal interest of any nature or kind in any related product, service, and/or company. Title: Clonal Expansions of CD8(+) T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection\nPassage: Following aerogenic infection of CBA/J and C57BL/6 mice with Mtb we observed a gradual accumulation of CD4 + T cells in the lungs of C57BL/6 mice and significantly fewer CD4 + T cells within the lungs of CBA/J mice , as we have previously described . In contrast to the reduced number of CD4 + T cells, CBA/J mice demonstrated a significant late accumulation of CD8 + T cells within the lungs as Mtb infection progressed , eventually reaching or surpassing the number of pulmonary CD8 + T cells observed in C57BL/6 mice. This late accumulation was absent from C57BL/6", "Title: Gain-of-Function Research: Ethical Analysis\nPassage: were published in 2012. Advocates of these studies/publications argued that they would improve surveillance of H5N1 in nature and facilitate development of vaccines that might be needed to protect against pandemic strains of the virus. Critics questioned the validity of claims about such benefits and argued that the studies might facilitate creation of biological weapons agents that could kill millions, or possibly even billions, of people. Title: Why language matters: insights and challenges in applying a social determination of health approach in a North-South collaborative research program", "Passage: serve as outcome to measure quantitatively. We therefore set out to build the infrastructural capacity, while promoting the use of the material, leaving rigorous evaluation to a future date. Traditional epidemiology would consider this study a failure; however, the research process itself brought together communities, non-governmental organizations, national government and international agencies, serving to raise the level of awareness and conferring some empowerment to serve as a basis for future challenges to detrimental social processes. Table 3 assessed this collaborative research project with respect to the 4 S framework. Title: Globalization and Health: developing the journal to advance the field", "Passage: review of all the articles that have been published to date. The purpose of this review was to identify strengths, trends and current gaps in research; highlight opportunities for strengthening existing research; and to propose upcoming areas of research, projected to be of increasing importance over the next ten years. Title: Gain-of-Function Research: Ethical Analysis\nPassage: Some argued that publishing studies like these in full detail provided ''recipes'' for especially dangerous potential biological weapons agents to would-be bioterrorists. Many who acknowledged such potential dangers, on the other hand, argued that benefits of publication outweighed risks involved.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: more selectively, interpreted as indicating their importation along with foreign pilgrims. Over time, increased influenza vaccination has been credited for a fall in the prevalence of influenza like illnesses among Hajj pilgrims. A LRT sample is often not collected for these studies , so false negative findings are a possibility although little is known about the initial site of MERS-CoV infection and replication; it may have been assumed it was the LRT because disease was first noticed there but the URT may be the site of the earliest replication. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Clinically suspected MERS cases may return negative results by RT-rtPCR. Data have shown one or more negative URT samples may be contradicted by further URT sampling or the use of LRT samples, which is preferred . Higher viral loads occur in the LRT compared to the URT. This fits with the observation that the majority of disease symptoms are reported to manifest as systemic and LRT disease . However, on occasion, even LRT specimens from MERS cases may initially be negative, only to later become positive by RT-PCR . This may be due to poor sampling when a cough is", "Title: Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5\nPassage: DAMAVER envelope appears as a pear shaped structure in which the homologous model can be fitted. Additional envelope volume is visible close to the endonuclease domain, implying that it adopts multiple conformations in solution. Title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy", "Passage: which of which is slightly bigger than the other. Previous studies that produced recombinant nucleocapsid-like structures showed that expressed VP24 and VP35 both independently associate with NP, but that all three proteins together are necessary to produce ,50 nm diameter helical nucleocapsid-like structures. When VP35, VP30, VP24, and NP were transfected together, approximately 50 nm diameter helical nucleocapsid-like structure was also generated, whereas NP alone generated helical NP-RNA complexes ,20-25 nm in diameter, which were nuclease sensitive . Taken together these results suggest that VP24 and VP35 are the structural components of the bridge located on the periphery of the Title: Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5", "Passage: 24 from which we made the 5\u2032-vRNAp corresponding to the 5\u2032-end and it's 3\u2032 equivalent called 3\u2032-vRNAp . By thermal shift assay experiments, a 10 \u00b0C stabilisation was observed when 5\u2032-vRNAp was added to all the constructs, whereas when 3\u2032-vRNAp was added, the effect was less significant and dependent on the construct. Similar data had already been published 32 . Title: Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5\nPassage: which the 5\u2032-vRNAp binding site is located between the PA and PB1 subunits 5,6 . The 3\u2032-vRNA, on the other hand, interacts with all three subunits suggesting a sequential vRNAp binding mechanism.", "Title: Coinfection and Mortality in Pneumonia-Related Acute Respiratory Distress Syndrome Patients with Bronchoalveolar Lavage: A Prospective Observational Study\nPassage: Of the 142 pathogen-positive patients, 55 had bacterial, 88 had viral, and 81 had fungal pathogens . A total of 55 bacterial pathogens were identified in 42 patients: two pathogens were identified in eight patients, and three pathogens in two patients. Gram-negative bacteria were more common than gram-positive bacteria vs. n \u00bc 10 ). The most common gram-negative and gram-positive bacteria were P aeruginosa and methicillinresistant S aureus, respectively. A total of 88 viral pathogens were identified in 82 patients: two pathogens were identified in six patients. The most common virus was CMV, followed by influenza. A total of 81 Title: Detection of Common Respiratory Viruses and Mycoplasma pneumoniae in Patient-Occupied Rooms in Pediatric Wards", "Passage: In conclusion, the common respiratory pathogens RSV, influenza A virus, adenovirus, and M pneumoniae were detected in the air and/or on the surfaces of the objects in the rooms occupied by pediatric patients infected with the corresponding pathogen. It cannot be overemphasized that appropriate infection control measures should be strictly implemented when caring for such patients. Title: Year in review 2013: critical care - respiratory infections", "Passage: Choi and associates studied the role of viruses in 198 patients with severe pneumonia using RT-PCR and BAL fluid or nasopharyngeal swab . Of the patients, 35.9% had positive bacterial culture, 36.4% had viral infections, and 9.1% had bacterialviral co-infections. Rhinovirus was the most commonly identified virus , followed by parainfluenza virus and human metapneumovirus . Bacterial coinfection was more common with parainfluenza and influenza viruses and less common with respiratory syncitial virus and rhinoviruses. There was no difference in mortality between each group, but of those patients with viral infection, rhinovirus was associated with the highest mortality , followed Title: Detection of Common Respiratory Viruses and Mycoplasma pneumoniae in Patient-Occupied Rooms in Pediatric Wards", "Passage: Viral infections of the respiratory system are very common. In Taiwan, the predominant viruses isolated from patients with respiratory infections are enterovirus, respiratory syncytial virus , influenza A and B viruses, adenovirus, cytomegalovirus, herpes simplex virus-1, and parainfluenza virus. 27 Enterovirus causes herpangina, hand-foot-and-mouth disease, myocarditis, encephalitis, and death. RSV is the most common pathogen of the lower respiratory tract in infants 28 and a common cause of nosocomial infections in pediatric wards. 29 Influenza A and B viruses cause seasonal epidemics in Taiwan, especially in winter. 30 Adenovirus causes acute respiratory tract infections in children younger than 5 years", "Title: Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico\nPassage: Fifty randomly selected cases were asked to participate in the study from which 42 accepted participation. All approached controls agreed to participate. In total 126 individuals were recruited. Our drop-out rate was lower than 1% since one participant did not finish the follow-up due to the loss of the assigned GPS logger. Table 1 describes the main characteristics of the subjects in each group. No statistically significant differences were observed in most of variables except in age, since cases were significantly younger than the intradomestic or population controls . Title: Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review", "Passage: Most of the studies were set in the United States , followed by Canada , France , Japan , the Netherlands and England . Only one study was conducted in more than one country . Title: Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel\nPassage: A total of 180 cases and 532 controls were included in the study population. Eight cases could only be matched to 2 controls. Table 1 shows the distribution of cases and controls by demographic factors. Overall, about 83% were males, 49% were whites, 44% were blacks, over 57% were younger than 25 years, 10% were older than 35 years, about 12% were Hispanic, and over 56% were in the army. Approximately 35% of cases had greater than 3 years of military service. Title: A Literature Review and Survey of Childhood Pneumonia Etiology Studies: 2000\u20132010", "Passage: these, 6 studies were being conducted in Bangladesh; 5 in each of Brazil, India and Nepal; 4 in Indonesia; 3 in each of Kenya, Mozambique, South Africa, the United States, Australia, Thailand and Spain; and 2 in each of Jordan, Guatemala, China and Israel. Two studies reported that they obtained approval to collect postmortem specimens in their protocols, but neither site had collected any postmortem specimens as of March 2011. Additional study characteristics are reported in Supplementary Table 1 .", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The key limitations of genetic material detection are the lack of knowledge of the presence of viable virus, the potential cross-reactivity with non-specific genetic regions and the short timeframe for accurate detection during the acute infection phase. The key limitations of serological testing is the need to collect paired serum samples from cases under investigation for confirmation to eliminate potential cross-reactivity from non-specific antibodies from past exposure and/or infection by other coronaviruses. The limitation of virus culture and isolation is the long duration and the highly specialized skills required of the technicians to process the samples. All patients recovered. Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: implemented with the abovementioned conditions. The critical issue that follows is then how limited resources such as antiviral drugs and testkits can be used effectively with those conditions. Title: How necessary is a fast testkit for mitigation of pandemic flu?\nPassage: which any policy maker would try to minimize. This is especially true for antiviral drugs, which often represents a hard constraint. Depending on the frequency and proportion of such false positives, proper diagnostic approaches can then be implemented. For instance, when the proportion of false positives is high, such as the case of a high ILI rate, assuming that all patients are pandemic positive would put a strain on the limited drug supplies. Of course, such rates may not be possible to obtain for a novel pandemic strain with no outbreak history. Nonetheless, by not advocating a blanket approach and Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Rapid diagnostics plays an important role in disease and outbreak management. The fast and accurate diagnosis of a specific viral infection enables prompt and accurate public health surveillance, prevention and control measures. Local transmission and clusters can be prevented or delayed by isolation of laboratory-confirmed cases and their close contacts quarantined and monitored at home. Rapid diagnostic also facilitates other specific public health interventions such as closure of high-risk facilities and areas associated with the confirmed cases for prompt infection control and environmental decontamination .", "Title: Examining the knowledge, attitudes and practices of domestic and international university students towards seasonal and pandemic influenza\nPassage: Students attending the main campus of the university were approached to participate in the study. Two methods were used to identify potential participants. Firstly, the interviewer directly approached a convenience sample of students who were located in the food halls and recreation areas of the university campus and invited them to participate. In the latter half of the study, a snowball approach was used. The snowball approach was adopted due to problems with identifying and recruiting postgraduate students. They constitute a considerably smaller percentage of the total student body, often are enrolled externally and attend classes in the late afternoon/evening. Title: Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden", "Passage: The invitees registered themselves as participants on the study's website, via a specially designed interactive voice response telephone service , or by sending in a postal response form. Individuals who stated, in response to the invitation or the first questionnaire , that they were not currently working were excluded due to non-eligibility. After one reminder, the final cohort comprised 2,237 participants. Fig 2 shows the study flow diagram of recruitment, enrolment and follow-up. The study protocol was approved by the Regional Ethics Review Board in Stockholm, Sweden . All participants gave their written informed consent. Title: Participant retention practices in longitudinal clinical research studies with high retention rates", "Passage: Of the 19 participating studies, 13 were prospective cohort studies, 5 were RCTs, and 1 was a quasiexperimental study . Included studies had diverse patient populations, including victims of intimate partner violence, persons living with human immunodeficiency virus and acquired immunodeficiency syndrome , survivors of critical illness and other serious illnesses. The target sample size for studies ranged from 255-10,000. Actual sample recruitment at the time of interview ranged from 205 for the Community Aging in Place -Advancing Better Living for Elders study with older adults aging in place to 2528 for the Alzheimer's Disease Anti-Inflammatory Prevention Trial . Though Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: Should more than a third of the expected household members refuse to participate, the particular household will be excluded from the study. However, this will not apply if members are away from the household for extended periods due to work or school.", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: There are elements with zero genes that fulfill many criteria for early life: ribozymes, catalytic RNAs closely related to viroids. They were recovered in vitro from 10 15 molecules , 220 nucleotides in length, by 10 rounds of selection. Among the many RNA species present in this collection of quasispecies RNAs were catalytically active members, enzymatically active ribozymes. The sequence space for 220-mer RNAs is about 3 \u00d7 10 132 . Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even Title: Deciphering Biosignatures in Planetary Contexts", "Passage: The different possibilities for the emergence of membranebased compartmentalization have led to a significant research effort to build prebiotically plausible synthetic cell analogues that are capable of mimicking certain aspects of extant life . Analogs demonstrating metabolism, growth, replication, division, and evolution have been devised in the laboratory. These research efforts not only describe plausible options for the earliest forms of life on Earth but also lead to questions of how life can be defined in general terms and pose questions about the kind of compartments and their components that could be considered unambiguous extraterrestrial biosignatures. Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: Text: Mycoplasma mycoides by systematic deletion of individual genes resulted in a synthetic minimal genome of 473 genes . Can one consider simpler living entities?", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: More recently, peptide-displaying phage have been used in attempts to generate therapeutic antibody responses for chronic diseases, cancer, immunotherapy, and immunocontraception. Immunization with phage displaying Alzheimer's disease \u03b2-amyloid fibril peptides elicited anti-aggregating antibodies in mice and guinea pigs , possibly reduced amyloid plaque formation in mice , and may have helped maintain cognitive abilities in a transgenic mouse model of Alzheimer's disease ; however, it remains unclear how such antibodies are proposed to cross the blood-brain barrier. Yip et al. found that antibodies raised in mice against an ERBB2/HER2 peptide could inhibit breast-cancer cell proliferation. Phage displaying peptide ligands of Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: More recently, peptide-displaying phage have been used in attempts to generate therapeutic antibody responses for chronic diseases, cancer, immunotherapy, and immunocontraception. Immunization with phage displaying Alzheimer's disease \u03b2-amyloid fibril peptides elicited anti-aggregating antibodies in mice and guinea pigs , possibly reduced amyloid plaque formation in mice , and may have helped maintain cognitive abilities in a transgenic mouse model of Alzheimer's disease ; however, it remains unclear how such antibodies are proposed to cross the blood-brain barrier. Yip et al. found that antibodies raised in mice against an ERBB2/HER2 peptide could inhibit breast-cancer cell proliferation. Phage displaying peptide ligands of Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: a diagnostic and therapeutic reagent for Alzheimer's disease and Parkinson's disease due to the unanticipated ability of the phage to penetrate into brain tissue . Similarly, phage displaying an immunodominant peptide epitope derived from myelin oligodendrocyte glycoprotein depleted pathogenic demyelinating antibodies in brain tissue in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis . The advantages of the filamentous phage in this context over traditional antibody-drug or protein-peptide conjugates are its ability to carry very high amounts of drug or peptide, and its ability to access anatomical compartments that cannot generally be reached by systemic administration of a protein. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: a diagnostic and therapeutic reagent for Alzheimer's disease and Parkinson's disease due to the unanticipated ability of the phage to penetrate into brain tissue . Similarly, phage displaying an immunodominant peptide epitope derived from myelin oligodendrocyte glycoprotein depleted pathogenic demyelinating antibodies in brain tissue in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis . The advantages of the filamentous phage in this context over traditional antibody-drug or protein-peptide conjugates are its ability to carry very high amounts of drug or peptide, and its ability to access anatomical compartments that cannot generally be reached by systemic administration of a protein.", "Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus\nPassage: easy-to- use system . Our reBmBac system has two major improvements relative to this system. First, the fragment replaced during homologous recombination in our reBmBac system is only a 1.2 kb tet R gene. In contrast, the fragment in bBpGOZA is more than 6 kb, and it contains a miniF replicon and a kan R gene. Second, the CopyControl origin in our system facilitates the large-scale preparation of high-quality reBmBac DNA. Our results over the course of many experiments indicated that the high quality of reBmBac DNA and transfer plasmid DNA are key factors for achieving good recombination results. We Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Similarly, recombinant antibodies have several advantages: bacteria, yeast, plants, or animals can be used to produce antibodies, no need for immunization, and intrinsic properties can be modified easily using mutagenesis techniques. Genetically engineered antibodies have integral characteristics that suit various downstream applications or can be converted into functional whole immunoglobulins . Antibodies exhibit strong immunity to defend against foreign antigens and non-selfagents. However, a variety of recombinant antibodies is needed to interact these hostile antigens. Over the last decade, the use of antibody engineering or recombinant antibody technology has shaped the genetic manipulation of a diverse range of antibody fragments Title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA", "Passage: Manipulation of BACs using traditional cloning procedures can be difficult and thus a range of methodologies that apply bacterial genetics, including homologous recombination within the E. coli host, have been developed ). The use of homologous recombination allows site-directed mutagenesis of BACs and, by employing a counterselection scheme, specific modifications can be obtained without leaving residual \"foreign\" sequences . The main advantage of this method is that there are no target limitations and no need for suitable restriction sites. The integration of the modified sequence is performed in vivo thereby potentially being more accurate than in vitro approaches like PCR-based Title: DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections", "Passage: A distinct approach to antibody immune therapy which would allow for simplicity of production and lower costs, with high stability and ease of deliverability could be advantageous. In this regard, the technology of DNA-encoded protein antigen delivery has specific advantages as demonstrated by recent successes in the DNA vaccine field: plasmid DNA is well-tolerated and nonintegrating, it does not require cold-chain distribution, it can be delivered repeatedly, and it is relatively inexpensive to produce. 13 However, to date, the ability to produce substantial levels of protein expression systemically from in vivo delivery of plasmid DNA has not been considered feasible.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: The findings of our study, conducted over a 5-year period at five geographically dispersed sites in the USA, demonstrate that human coronavirus is an important cause of influenza-like illness ranged from 4% to 22%. 14 Additionally, we found HCoV-OC43 Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Prior to December 2019, 6 CoVs were known to infect human, including 2 \u03b1CoV and 4 \u03b2CoV (HCoV-OC43 [", "Title: CDC Summary 21 MAR 2020,\nPassage: People who get a fever or cough should consider whether they might have COVID-19, depending on where they live, their travel history or other exposures. More than half of the U.S. is seeing some level of community spread of COVID-19. Testing for COVID-19 may be accessed through medical providers or public health departments, but there is no treatment for this virus. Most people have mild illness and are able to recover at home without medical care. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Symptoms at the point of diagnosis were reported for 31 cases. Two cases were asymptomatic and remained so until tested negative. The asymptomatic cases were tested as part of screening following repatriation and during contact tracing respectively. Of the remaining 29, 20 reported fever, 14 reported cough and eight reported weakness. Additional symptoms reported included headaches , sore throat , rhinorrhoea , shortness of breath , myalgia , diarrhoea and nausea . Fever was reported as the sole symptom for nine cases. In 16 of 29 symptomatic cases, the symptoms at diagnosis were consistent with the case definition for acute Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: The 2019-nCoV infected cases have symptoms like fever, fatigue, dry cough, dyspnea etc., with or without nasal congestion, runny nose or other upper respiratory symptoms . Despite the atypical symptoms were reported , Nan-Shan Zhong, the academician of Chinese Academy of Engineering in an exclusive interview with Xinhua News Agency on 28 January 2020, pointed out that fever is still the typical symptom of 2019-nCoV infection. Title: CDC Summary 21 MAR 2020,", "Passage: The complete clinical picture with regard to COVID-19 is not fully known. Reported illnesses have ranged from very mild to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, a reportexternal icon out of China suggests serious illness occurs in 16% of cases. Older people and people of all ages with severe chronic medical conditions \u2014 like heart disease, lung disease and diabetes, for example \u2014 seem to be at higher risk of developing serious COVID-19 illness. A CDC Morbidity & Mortality Weekly Report that looked at severity of disease among COVID-19", "Title: Can \"presumed consent\" justify the duty to treat infectious diseases? An analysis\nPassage: In both of the universities in which this study was conducted there are ethics committees which had been established for the purpose of determining the ethical appropriateness of pharmaceutical trials using humans; since our study involved only the use of a questionnaire and not an experimental drug, we did not apply for approval from either of these ethics committees. Instead, written permission to carry out the study was granted by the dean of the faculty of medicine and by the chief manager of university hospitals. In addition, all of the potential participants were fully informed about the aim and structure Title: Innovations in research ethics governance in humanitarian settings", "Passage: What are your plans for obtaining consent? A requirement to inform participants is often seen as being an important way to show respect and promote patient autonomy and welfare. 2) Ensure that consent procedures are acceptable within the study community . Title: Can \"presumed consent\" justify the duty to treat infectious diseases? An analysis\nPassage: of the study. Furthermore, potential volunteers were all made aware that participation was strictly voluntary and that all of the answers they provide would be done so anonymously. Title: Innovations in research ethics governance in humanitarian settings", "Passage: d. How will the consent process be conducted? You may want to consider issues such as: who will consent, where they will do so , will a witness to the consent be required, how much time will be offered to consider whether to be involved? Prior engagement with communities can be a useful way to ensure that the consent process meets local expectations and sensitivities. How will the act of consent be recorded ?", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus virus) and a H1N1pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection. CONCLUSION: A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: We found that the combination of carrageenan with 3 mg/kg BW/day Zanamivir used for treatment of H7N7 infected mice resulted in significantly enhanced survival of mice in comparison to both mono-therapies . The significantly enhanced survival compared to the placebo treated group was also found after a delayed treatment start 48 hpi. Furthermore, in the H1N1pdm model the combination of carrageenan with 1 mg/kg BW/day Zanamivir showed statistically significant enhanced survival in comparison to placebo treatment even after a treatment start 72 hpi. This is a remarkable finding since NIs are normally not effective when applied 72 hpi. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: virus which has caused more than 175 deaths until October 2014 . Second, they are of special interest for the carrageenan/Zanamivir combination approach. They have shown to differ in in-vitro susceptibility to carrageenan, Zanamivir and the combination thereof . While H1N1pdm was highly sensitive to inhibition by both substances alone, H7N7 required much higher concentrations of carrageenan and Zanamivir, respectively, to achieve similar inhibition efficiencies. Therefore, both virus strains were chosen to further explore the efficiency of the combination therapy in a mouse model. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: In summary, the combination of two effective, established mono-therapies resulted in a significantly enhanced survival in lethally H7N7 infected mice. Additionally, the combination therapy was highly efficient in comparison to placebo treatment even after a treatment onset up to 48 hpi.", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: ELISA-array. The ELISA-array assay is based on a \"sandwich\" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: The identical antibodies used in the ELISA-array format were also tested in a conventional ELISA format to determine the difference in sensitivity and specificity of the two methods. The conventional ELISAs were performed at the same time as the ELISA-array assays to ensure similar reaction conditions. The conventional ELISAs were performed in an identical maner to the ELISA-array, except that antibodies were coated at a concentration of 2 \u03bcg/mL in PBS , and substrate TMB was used instead of Super Signal ELISA Femto Maximum sensitive substrate . Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: Optimization of the ELISA-array assay Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Antibody arrays for simultaneous multiple antigen quantification are considered the most accurate methods . Liew validated one multiplex ELISA for the detection of 9 antigens; Anderson used microarray ELISA for multiplex detection of antibodies to tumor antigens in breast cancer, and demonstrated that ELISA-based array assays had the broadest dynamic range and lowest sample volume requirements compared with the other assays.", "Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: Pertussis symptom duration and severity were mild compared with the classic pertussis case presentation. Only 3 of the 17 cases fulfilled the WHO criteria, which requires a minimum of 2 weeks of cough, whoop, or posttussive vomiting . Studies on pertussis in infants have generally been clinic-based, hospital-based, or in an outbreak, which therefore required a certain severity of illness for parents to recognize a need for medical attention . These study designs and passive surveillance efforts therefore may have missed milder pertussis cases . Our study, which required only 1 respiratory symptom for a nasal swab to be collected, Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: Although cough, difficulty breathing, and cough with vomit were the most common symptoms, no symptom was present in all B pertussis cases. During an epidemic period in Washington state, among infants <1 year, who had a minimum of 14 days cough plus an additional symptom, 82% had posttussive emesis, 29% had apnea, 26% had whoop, and 42% had cyanosis . A study of US neonates with pertussis showed the symptom prevalence to be 97% for cough, 91% for cyanosis, 58% for apnea, and 3% for fever . Our study found lower or equal symptom prevalence with the exception of fever. Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: respiratory symptom criteria. Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: Infant respiratory symptoms were reported by parents, who may have missed signs that might have been observed by a healthcare worker. However, the criteria for collection of the nasal swab were broad and did not require sophisticated clinical skills. However, apnea and cyanosis may have been difficult for parents to identify. Although the criteria for specimen collection changed in year 2, no infant experienced a pertussis-specific symptom in isolation without also having one of the originally specified respiratory symptoms. These data support our assumption that we were unlikely to have missed pertussis cases in year 1 with our less sensitive", "Title: Evaluation of TaqMan qPCR System Integrating Two Identically Labelled Hydrolysis Probes in Single Assay\nPassage: striking examples were shown in Fig. 6 . Title: Evaluation of TaqMan qPCR System Integrating Two Identically Labelled Hydrolysis Probes in Single Assay\nPassage: presented approach in diagnostic qPCR was demonstrated on practical examples. Title: A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve\nPassage: was also due to decreased dissociation rates, while association rates were equal . Title: Model of the pathway of \u22121 frameshifting: Long pausing\nPassage: and simultaneously provided a consistent explanation of a lot of available independent experimental data.", "Title: Viral vector-based influenza vaccines\nPassage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: The ability of human adenoviruses to induce strong innate and adaptive immune responses makes them powerful adjuvants that facilitate the immune response against an encoded antigen. Recombinant adenoviruses have been shown to elicit significant immune responses to bacterial , viral and tumour-associated antigens . While these results are encouraging, immunity eventually develops against virus capsid proteins. This severely reduces the immunogenicity of adenovirus-based vaccines in mice, , primates and humans . This problem is also significant since a large portion of the Western world has marked levels of anti-adenovirus serotype 5 antibodies and is also prominent in regions of sub-Saharan Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adenovirus vectors are attractive as vaccine vectors because their genome is very stable and there are a variety of recombinant systems available which can accommodate up to 10 kb of recombinant genetic material . Adenovirus is a non-enveloped virus which is relatively stable and can be formulated for long-term storage at 4 \u00b0C, or even storage up to six months at room temperature . Adenovirus vaccines can be grown to high titers, exceeding 10 1\u00b0 plaque forming units per mL when cultured on 293 or PER.C6 cells , and the virus can be purified by simple methods . Adenovirus vaccines Title: Adenovirus flow in host cell networks", "Passage: regard, AdVs are a robust family, composed of more than 100 known serotypes that can infect various vertebrate species including mammals, birds, fish, reptiles and amphibians . To date, there are at least 57 serotypes divided into seven species that can infect humans, causing acute respiratory disease, gastroenteritis, keratoconjunctivits and even obesity . These diseases are generally self-limiting, but severe and deadly infections can occur in immunocompromised hosts . Cell biology studies using optimized tissue culture systems have shown that typical times for producing AdV virions from infected cells ranges from 14 to 19 h depending on serotype , though", "Title: Animal lectins: potential receptors for ginseng polysaccharides\nPassage: 1.6.1. P-type lectins P-type lectins are intracellular transmembrane glycoproteins with specificity for mannose-6-phosphate to identify and route lysosomal enzymes to the lysosomal compartment and they have two groups. One is the 43e46 kDa cationdependent M6P receptor which requires Ca 2\u00fe for activity and contains single extracellular domain, followed by a single transmembrane domain . The other is the 275e300 kDa Table 2 A summary of the C-type lectin receptors dealt with in this review insulin-like growth factor II/cation-independent M6P receptor which does not require cation for activity and has a large extracellular domain containing two high-affinity binding sites . The Title: Find novel dual-agonist drugs for treating type 2 diabetes by means of cheminformatics", "Passage: G-protein-coupled receptors-grey incident degree analysis and G-protein-coupled receptors -2-layer predictor for identifying G protein-coupled receptors and their types, 25, 26 iLoc-Euk and iLoc-Hum for predicting subcellular localization of eukaryotic and human proteins, 27,28 NR-2L for identifying nuclear receptors and their subfamilies, 29 ProtIdent for identifying proteases and their types, 30 and HIVcleave for predicting human immunodeficiency virus protease cleavage sites in proteins, 31, 32 can provide timely and very useful information, as well as insights for drug development. In addition to the aforementioned approaches, the Virtual Screening technique and Core Hopping technique are also very useful. The former can be Title: Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses", "Passage: fusion and cell-cell fusion are distinct receptor mediated phenomena. The possible contribution of differential glycosylation to these phenotypic differences was evaluated using Western analysis, treatment by glycosylation inhibitors and mutagenesis to remove glycosylation sites. Title: Animal lectins: potential receptors for ginseng polysaccharides\nPassage: has the capacity for endocytosis of ligands from the cell surface and serves to turn over IGF by endocytosis, but not CD-MPR .", "Title: The Role of Interleukin-1 cytokine family (IL-1\u03b2, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis\nPassage: IL-1 is a polypeptide which has two forms; IL-1\u03b1 and IL-1\u03b2. It is involved in the acutephase response and is accountable for several alterations that are related to the onset of various medical disorders . It is demonstrated recently that higher levels of IL-1\u03b2 cytokine are strongly associated with surgically treated mycetoma patients, in comparison to those treated without surgery . It is known that IL-1\u03b2 is a pro-inflammatory cytokine that is involved in cell death coordination . IL-1\u03b2 cytokine is cleaved into the mature, active form primarily by inflammasome dependent caspase activity . It is possibly that mature IL-1\u03b2 Title: The Role of Interleukin-1 cytokine family (IL-1\u03b2, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis", "Passage: IL-1\u03b2, IL-37, and IL-12 were measured in the sera using commercially available enzyme linked immunosorbent assay kits . Serum levels of IL-35 were estimated using a sandwich ELISA commercial kit . Cytokine assays were performed in duplicates according to the manufacturers' protocols. The sensitivity of Human ELISA kits for IL-1\u03b2, IL-37, IL-12 and IL-35 cytokines was 0.5 pg/ml. Title: The Role of Interleukin-1 cytokine family (IL-1\u03b2, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis", "Passage: IL-37, which is a member of the IL-1 family, has emerged as a potent anti-inflammatory cytokine that suppresses both innate and adaptive immune responses . Its role in human diseases is not completely understood yet . However, the anti-inflammatory properties of IL-37 have been associated with inflammatory diseases, such as systemic lupus erythematosus , and inflammatory bowel disease . It has been reported that IL-37 is negatively associated with pro-inflammatory cytokines such as IL-1\u03b2, IL-6, IL-17, TNF-\u03b1 and IFN-\u03b3 in peripheral blood mononuclear cells of patients with degenerative intervertebral discs and Graves' disease . IL-37 protein level in PBMCs and Title: The Role of Interleukin-1 cytokine family (IL-1\u03b2, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis", "Passage: IL-35 is a recently identified heterodimeric cytokine which belongs to the IL-12 cytokine family, composed of the subunits of IL-27; \u03b2 chain Epstein-Barr-virus -induced gene 3 and IL-12\u03b1 chain p35 . IL-35 is a potent immunosuppressive cytokine produced by B regulatory cells , DCs , and to a lesser extent, by endothelial cells, smooth muscle cells, and monocytes . The biological effect of IL-35 is poorly understood, however IL-35 is recognised as a typical anti-inflammatory cytokine, and the predominant mechanism of suppression is associated with its ability to suppress T cell proliferation and effector functions . Given the direct immunosuppressive", "Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus\nPassage: easy-to- use system . Our reBmBac system has two major improvements relative to this system. First, the fragment replaced during homologous recombination in our reBmBac system is only a 1.2 kb tet R gene. In contrast, the fragment in bBpGOZA is more than 6 kb, and it contains a miniF replicon and a kan R gene. Second, the CopyControl origin in our system facilitates the large-scale preparation of high-quality reBmBac DNA. Our results over the course of many experiments indicated that the high quality of reBmBac DNA and transfer plasmid DNA are key factors for achieving good recombination results. We Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Similarly, recombinant antibodies have several advantages: bacteria, yeast, plants, or animals can be used to produce antibodies, no need for immunization, and intrinsic properties can be modified easily using mutagenesis techniques. Genetically engineered antibodies have integral characteristics that suit various downstream applications or can be converted into functional whole immunoglobulins . Antibodies exhibit strong immunity to defend against foreign antigens and non-selfagents. However, a variety of recombinant antibodies is needed to interact these hostile antigens. Over the last decade, the use of antibody engineering or recombinant antibody technology has shaped the genetic manipulation of a diverse range of antibody fragments Title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA", "Passage: Manipulation of BACs using traditional cloning procedures can be difficult and thus a range of methodologies that apply bacterial genetics, including homologous recombination within the E. coli host, have been developed ). The use of homologous recombination allows site-directed mutagenesis of BACs and, by employing a counterselection scheme, specific modifications can be obtained without leaving residual \"foreign\" sequences . The main advantage of this method is that there are no target limitations and no need for suitable restriction sites. The integration of the modified sequence is performed in vivo thereby potentially being more accurate than in vitro approaches like PCR-based Title: DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections", "Passage: A distinct approach to antibody immune therapy which would allow for simplicity of production and lower costs, with high stability and ease of deliverability could be advantageous. In this regard, the technology of DNA-encoded protein antigen delivery has specific advantages as demonstrated by recent successes in the DNA vaccine field: plasmid DNA is well-tolerated and nonintegrating, it does not require cold-chain distribution, it can be delivered repeatedly, and it is relatively inexpensive to produce. 13 However, to date, the ability to produce substantial levels of protein expression systemically from in vivo delivery of plasmid DNA has not been considered feasible.", "Title: Effectiveness of Integrative Therapy for Parkinson\u2019s Disease Management\nPassage: result from genetic and ethnic differences, but the possibility of the effects of CAM, including KM, cannot be ruled out. Title: Effectiveness of Integrative Therapy for Parkinson\u2019s Disease Management\nPassage: were compared. After PS matching, the characteristics of both groups were statistically similar . Title: Effectiveness of Integrative Therapy for Parkinson\u2019s Disease Management", "Passage: It should be noted that this paper had several limitations. First, the number of subjects was not sufficient because of data limitations; therefore, we cannot be sure of whether the non-significance of results is due to the absence of a relationship between the groups or to a lack of statistical power. Accordingly, comparative studies with increased duration and number of patients are required to clarify the effects KM on PD. Second, we assessed whether PD and its complications have been wellcontrolled by alternative outcomes-related measures such as the prevalence of hospitalization and annual length of hospitalization after PD diagnosis. Generally, Title: Effectiveness of Integrative Therapy for Parkinson\u2019s Disease Management\nPassage: in PD patients .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: encoded protein in comparison to native mRNAs . N protein has been increasingly linked to viral replication and translation, sometimes in previously unanticipated ways. It is among a growing family of diverse viral proteins that can serve as a nonspecific -RNA chaperone\u2016, an activity that should facilitate the L polymerase's access to vRNA for transcription and replication, in that it can transiently dissociate misfolded RNA structures . Some of N protein's effects on translation might not immediately be recognized to be adaptive in nature. It can replace the entire EIF4F translational initiation complex, simultaneously presenting the ribosome with a replacement Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: be quickly cleared or rendered less competent in its replication so as to blunt any pathological response in the host . The anti-hantavirus innate response can in some cases be attributed to viral interaction as a ligand of TLR-3, but not in others, and in endothelial cells, it appears not to require more than the viral particle itself, even when introduced in replication-incompetent form . Proteins and mRNAs prominently induced by hantaviruses include MxA and IFIT-1 and others including some with known or suspected anti-viral activity. Those hantaviruses, often highly pathogenic strains, that fail to induce a potent antiviral response, Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: are suspected or presumed to have a potent interferon-pathway antagonism mechanism relative to other viruses, a mechanism that acts positively to prevent an effective innate response from forming, at least early in infection . Yet some instances are reported wherein highly pathogenic hantaviruses, such as SNV, are also able to induce expression of interferon-stimulated gene mRNAs, even very early in infection, with ISG proteins, as expected, taking longer to appear in the cell . Anti-interferon activities have also been attributed to the NSs protein that may be elaborated in cells infected by serotypes that encode this protein . Other investigators Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: Moreover, it is universally acknowledged that type I IFN responses are essential for hosts to defend against hantaviral infection. Multiple IFN stimulated genes were confirmed to have antihantaviral activity. The interferon-induced MxA protein, a GTPase with extensive antiviral activity, notably against influenza viruses, was reported to inhibit HTNV and PUUV replication in Vero cells . The interferoninduced IFITM3 protein was able to inhibit HTNV infection in both HUVEC and A549 cells by inhibiting virus entry . Several studies have shown that pretreatment with type I IFN could effectively inhibit hantaviral infection. Pretreating endothelial cells with IFN\u03b1 blocks hantavirus replication, and", "Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection\nPassage: The bacterial coinfection rate of 28% amongst our H1N1 hospitalized patients was higher compared to other studies . A large laboratory-based study in the United States demonstrated comparable bacterial coinfection rates to our study with similarly very low frequency of viral copathogen detection . Whilst our finding concurred with several studies that showed H1N1 infections having a predilection for younger patients, patients > 50 years had higher risk of bacterial coinfection in our study. Title: Severe novel influenza A (H1N1) infection in cancer patients", "Passage: In our study, we detected bacterial coinfection in seven of the eight patients. The CDC reported that 29% of fatal cases in the United States presented at least one bacterial coinfection . Mauad et al. found evidence of bacterial coinfection in 38% of fatal cases in Sao Paulo. Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection\nPassage: the actual number of cases. The preadmission antibiotic therapy could underestimate the bacterial coinfection rates. Despite these limitations, we identified bacteria coinfection in 28% of our patients. Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: A comparison between H1N1 patients with and without bacterial coinfection is shown in Table 2 . Although 90% of patients were < 50 years old, bacterial coinfection was more frequent in patients > 50 years . The presence of underlying comorbidity provided a suitable niche for bacterial coinfection . Although ICU admissions, mechanical ventilation, renal impairment, mortality and pneumonia were notably higher in patients with bacterial coinfection, they were not statistically significant. Other factors associated with bacterial coinfection in the univariate analysis were development of complications , liver impairment and supplemental oxygen requirement . Out of the 50 patients, 12", "Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics\nPassage: A Protease inhibitor, rupintrivir thats prevents cleavage of viral proteins required for replication was tested in an HRV challenge trial. Rupintrivir was well tolerated and reduced viral loads and respiratory symptoms . However, in studies of natural infection, it did not significantly affect viral loads or symptom severity . Title: Recent developments in antiviral agents against enterovirus 71 infection", "Passage: A pseudosubstrate, LVLQTM peptide, could inhibit EV-71 infection through binding to the active site of 2A protease . Rupintrivir is an irreversible peptidomimetic inhibitor of human rhinovirus 3C protease, which reached phase 2 clinical trials with promising outcomes . Rupintrivir showed significant inhibition of EV-71 infection in vitro and in vivo but with reduced efficacy as compared with human rhinoviruses . X-ray crystallography of the complex of EV-71 3C protease with rupintrivir revealed that the half-closed S2 sub-site and the size reduced S1\u2032 pocket of EV-71 3C protease limits the access of the rupintrivir's P1\u2032 group which contains a lactam Title: Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR", "Passage: All patients with influenza infection were treated with oseltamivir within 24 h of diagnosis. Influenza viral load after receiving treatment was significantly lower for both patients with influenza A and influenza B infections . Ribavirin was administered to 8 patients with RSV infection: 7 patients inhaled ribavirin, and 1 patient received intravenous ribavirin since the patient was on mechanical ventilation . Viral load was significantly reduced after completion of treatment. Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: Human rhinoviruses usually cause mild acute respiratory infections, but on occasions can also cause more severe respiratory infections, including exacerbations of asthma and COPD. Of 115 Japanese children with asthma, a respiratory virus was detected in 86%, of which HRV or RSV were most common. 79 Ex vivo bronchial epithelial cells from people with asthma are more susceptible to HRV infection, due to deficient induction of IFN-b and IFN-lambda. In a study of 147 asthmatics on inhaled corticosteroid therapy, with a history of virusassociated exacerbations, patients were randomised to 14-day treatment with inhaled IFN-b or placebo within 24 hours of", "Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs\nPassage: The chemiluminescent enzyme-linked immunosorbent assay was performed by detecting EBOV with the anti-EBOV VP40 antibody followed by staining with the horseradish peroxidase -conjugated goat anti-mouse secondary antibody . Chemiluminescence was quantified using Pico Chemiluminescent Substrate and a plate reader . Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: In addition to the fluorescent assay, we also implemented a CELIA using an HRP-labeled antibody, which amplified the signal and increased the sensitivity of virus detection. As expected, the CELIA showed an improvement in the quality of data sets compared to the fluorescent assay. S/N ratio and Z' factor were in an acceptable range as early as 24 hpi with the lowest virus input detected at an MOI of 0.1. An EC 50 could also be determined at this time point. At 48 or 72 hpi, the two fluorescent read outs were similar to the chemiluminescent read out. Title: A Fluorometric Method of Measuring Carboxypeptidase Activities for Angiotensin II and Apelin-13", "Passage: ELISA-based methods that measure the input of Ang II or the production of Ang-, or both, are available 12, 25 . However, antibody-based assays are intrinsically finicky and the input substrate peptide and the tissue lysate amount have to be carefully optimized to achieve linearity. Even with the best setting, the dynamic range is less than one order of magnitude, as opposed to the three orders of magnitude range achieved by the Ang II phenylalanine assay . The clinical importance of the RAAS in a multitude of diseases underscores the need for techniques to measure enzymatic activities in biological samples, Title: Statistical Evaluation of HTS Assays for Enzymatic Hydrolysis of \u03b2-Keto Esters", "Passage: second assay is also well-known and established for measurements of alcohol in food . This assay was miniaturized to microtiter plates. The third assay is a modification of a chromogenic alcohol-oxidase /peroxidase ethanol assay for determination of ethanol in beverages, which normally based on 2,2'-azino-bis as chromogenic substrate . This assay was modified to a luminometric assay by adding luminol instead of a chromogenic substrate. The luminometric measurements should be more sensitive due to photons are released by the detection reaction. For the first time the system was established in a flow system with separated bioreactors by Marschall and Gibson", "Title: A Global Champion for Health\u2014WHO\u2019s Next?\nPassage: WHO's next Director-General should be a proven leader and advocate, perhaps from a lowincome or middle-income country. The new recruit will be greeted by a full in-tray, and featuring prominently are likely to be the constraints imposed by WHO's current funding mechanisms. A substantial proportion of WHO's existing budget is earmarked for specific projects, leaving the organization with little financial flexibility to respond to unanticipated demands. However, any improved funding mechanism is likely to follow, and be dependent on, organizational reform. According to Kruk, \"WHO is both essential and hamstrung. . .the election of the Director-General should be a moment Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: Chan will step down from WHO on June 30, 2017 after more than a decade in the post. The process for choosing WHO's next leader has begun, promising to be protracted and rigorous as befits the importance of the role. Factoring in the many influential stakeholders in the process of appointing Chan's successor, however, transparency of the selection process may be one area unlikely to attract plaudits. Although too soon to speculate about the identity of WHO's next Director-General, it is worth reflecting on what qualities an incoming leader should bring to WHO and how that person might need to Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: global body will always be needed to promote, set standards in, and evaluate progress toward better health for people in all countries. The next Director-General will need to heed critics of the organization and craft a process of streamlining and restructuring to produce a new WHO that is demonstrably effective in leading responses to threats to health, and efficient in doing so. As Gostin commented to PLOS Medicine, \"WHO urgently needs a bold reform agenda to fix long-standing problems recognized by every independent group that has evaluated the Organization.\" Political machinations and the enemy within, bureaucracy, are likely to impede Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: Instead of electing a new Director-General, Lorenz Von Seidlein of Mahidol University, Thailand, argued that \"the problems. . .are now so deeply ingrained that replacing the WHO with new, more appropriate organizations is the logical solution. . .at a fraction of current cost, free of cumbersome, archaic obligations and entitlements and an ability to respond to new problems.\" This viewpoint is indicative of the strength of feeling that WHO's deficiencies have come to evoke in some of those committed to the cause of improving the health of people in low-income and middle-income countries. But this perception acknowledges that an accountable", "Title: Improved Global Capacity for Influenza Surveillance\nPassage: objectives and evaluate their influenza surveillance systems' data quality, flexibility, simplicity, stability, acceptability, and utility through training and technical assistance . Title: Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals", "Passage: When implementing a national response, the problem to be solved, reduced, changed or prevented must first be understood. Surveillance refers to the systematic collection of outcome-specific data \"\u2026for use in the planning, implementation, and evaluation of public health practice\" . Many countries have no or, at best only very basic, systems of surveillance that provide routine suicide data that is collected systematically and that can inform both programmatic targets for interventions and the development of policy initiatives. Significantly, many countries do not know the key methods used for suicide or the proportion of all suicides who have previously made attempts. Title: Steps to a Sustainable Public Health Surveillance Enterprise A Commentary from the International Society for Disease Surveillance", "Passage: 1. Recognize systematic and ongoing public health surveillance as a core public health function that is essential for population health, economic stability, and national security. 2. Create and support funding mechanisms that reinforce enterprise , rather than categorical surveillance infrastructures and activities in order to reduce inefficient silos, leverage resources, and foster synergies. 3. Oppose further cuts to spending for surveillance activities. 4. Invest in surveillance workforce development to build competencies and improve organizational capacity to utilize technological advances in surveillance practice. 5. Advance a rigorous surveillance research and evaluation agenda that will deepen the understanding of community health, identify Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats\nPassage: they target, predictive surveillance efforts are emergent, and there are numerous obstacles, both technical and organizational, that challenge their development.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: SARS-CoV that includes the split orf8b , civet SARS-CoV , two bat SARS-related-CoV containing full-length orf8 , 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5 ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Orf8 orf8 is an accessory protein found in the Betacoronavirus lineage B coronaviruses. Human SARS-CoVs isolated from early-phase patients, all civet SARS-CoVs, and other bat SARS-related CoVs contain fulllength orf8 . However, a 29-nucleotide deletion, Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Bat which causes the split of full length of orf8 into putative orf8a and orf8b, has been found in all SARS-CoV isolated from mid-and late-phase human patients . In addition, we have previously identified two bat SARS-related-CoV and proposed that the original SARS-CoV full-length orf8 is acquired from these two bat SARS-related-CoV . Since the SARS-CoV is the closest human pathogenic virus to the 2019-nCoV, we performed phylogenetic analysis and multiple alignments to investigate the orf8 amino acid sequences. The orf8 protein sequences used in the analysis derived from early phase SARS-CoV that includes full-length orf8 , the mid-and late-phase Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The first known MERS human-to-human transmission event was one characterized by acute LRT disease in a healthcare setting in Jordan. In stark contrast, a sero-survey of HCW who were sometimes in close and prolonged contact with the first, fatal MERS-CoV case in 2012 , found none of the HCW had seroconverted four months later, despite an absence of eye protection and variable compliance with required PPE standards . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: departments, treatment rooms, open intensive care facilities and private patient rooms. The nature and quality of air exchange, circulation and filtration are important variables in risk measurement and reduction as is the use of negative pressure rooms to contain known cases. Droplet spread between humans is considered the mechanism of human-to-human transmission and the need for droplet precautions was emphasized after the Al-Ahsa hospital, the KSA and the South Korean outbreaks . By extrapolation, aerosol-generating events involving DCs should be factored into risk measurement and reduction efforts and messaged using appropriate context. The provision of evidence supporting the best formulation Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: of \"contact\" during these interviews has been defined for one study . Despite this lack of clarity, the WHO consider that evidence linking MERS-CoV transmission between DCs to humans is irrefutable .", "Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The 2019 novel coronavirus , a betacoronavirus, forms a clade within the subgenus sarbecovirus of the Orthocoronavirinae subfamily . The severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus are also betacoronaviruses that are zoonotic in origin and have been linked to potential fatal illness during the outbreaks in 2003 and 2012, respectively . Based on current evidence, pathogenicity for 2019-nCoV is about 3%, which is significantly lower than SARS-CoV and MERS-CoV . However, 2019-nCoV has potentially higher transmissibility than both SARS-CoV and MERS-CoV . Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: SARS: severe acute respiratory syndrome", "Title: An implantable system for long-term assessment of atrial fibrillation substrate in unanesthetized rats exposed to underlying pathological conditions\nPassage: In the elevated plus maze test, there were significant differences between the groups in terms of Supplemental Figure S2 -I shows the mean startle amplitude of rats in response to the 30 startlepulses. There were significant differences between the groups =28.8, p<0.0001). Post hoc Bonferroni test revealed that isolation in both standard cages and in mesh barrier cages significantly increased the mean startle amplitude as compared to controls . Moreover, rats that had been isolated in mesh barrier cages significantly attenuated the hyperarousal response, eliciting a relative decrease in mean startle amplitude compared to the mesh barrier group . Title: Milk Lacking \u03b1-Casein Leads to Permanent Reduction in Body Size in Mice", "Passage: horizontally positioned pole which was erected slowly to vertical position. Animals falling off before reaching vertical position were recorded. Postural reflex: The animal was placed in an empty observation cage which was then gently shaken 3 times vertically and 3 times horizontally. The presence/absence of the natural reaction to this treatment was recorded. Title: Breaking the Waves: Modelling the Potential Impact of Public Health Measures to Defer the Epidemic Peak of Novel Influenza A/H1N1", "Passage: There are a number of possible public health measures that may be used to stop or slow down the spread. Border control has been extensively discussed in this context to delay the international spread of influenza. However, in order to achieve a significant delay, more than 99% of air travel would have to be stopped . As has been shown for SARS, entry screening methods are unlikely to detect more than 10% of imported infections and the positive predictive value of temperature screening is low especially at the beginning of a pandemic . It is therefore inevitable that importation occurs. Title: Quantifying social distancing arising from pandemic influenza\nPassage: thus discouraging people from getting out and circulating in the wider population .", "Title: Bibliometric analysis of publications on Campylobacter: (2000\u20132015)\nPassage: attached for those who are interested . Title: Outdoor environments and human pathogens in air\nPassage: At the first two meetings, participants were given a topic and asked to prepare a one-page literature review to support their presentations; each topic was assigned to two participants from different disciplines in order to ensure cross-disciplinarity of the discussion. These presentations now form the core of our review, and all the discussions from all the meetings were recorded. We have conducted an extended literature search and review to ensure that the content is representative, comprehensive and connected to the five main areas arranged below. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis", "Passage: Several limitations exist in our study. First, we characterised the knowledge structures generated by a large number of articles published in major medical journals that are included in the WoS database. However, our results are limited to a subset of all clinical-trial-related articles published in 40 leading medical journals. We suspect that these articles represent those that have great implications for clinical practice and that are relevant to clinical practice guidelines and healthcare regulators. Although the publication production analysed has been drawn from an exhaustive analysis of the biomedical literature, possibly, the search missed some relevant articles . Some reports Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: how the characteristics of the field change over time will be interesting to see.", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: Since there was no data on the proportion of asymptomatic infection of the virus, we simulated the baseline value of proportion of 0.5 . d) Since there was no evidence about the transmissibility of asymptomatic infection, we assumed that the transmissibility of asymptomatic infection was 0.5 times that of symptomatic infection , which was the similar value as influenza . We assumed that the relative shedding rate of A P compared to I P was 0.5. Thus, c = 0.5. e) Since 14 January, 2020, Wuhan City has strengthened the body temperature detection of passengers leaving Wuhan at airports, railway Title: Estimating human-to-human transmissibility of hepatitis A virus in an outbreak at an elementary school in China, 2011", "Passage: It is well-known that many infections with pathogens such as hepatitis A virus, influenza virus, Mycoplasma pneumoniae, and Mycobacterium tuberculosis are asymptomatic . For an outbreak caused by such pathogen, the only available data are about symptomatic infections or so at least at the early stage of the outbreak. Theoretically we can argue that if the proportion of symptomatic infections remains unchanged over the outbreak and there is no difference in transmissibility between symptomatic and asymptomatic infections, the estimate of R 0 based only on symptomatic cases should give similar results . In this study we test this for a Title: Quantifying social distancing arising from pandemic influenza\nPassage: of infectives who could have been asymptomatic transmitters. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: of asymptomatic infection was defined as \u03b4 P . The S P will be infected through sufficient contact with W and I P , and the transmission rates were defined as \u03b2 W and \u03b2 P , respectively. We also assumed that the transmissibility of A P was \u03ba times that of I P , where 0 \u2264 \u03ba \u2264 1.", "Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication\nPassage: Study has shown that about 40-80% of cats are detected with FECV shedding in their faeces . About 12% of these FECV-positive cats have developed immune-mediated fatal FIP disease . The prevalence of FIP among felines is due to continual cycles of infection and reinfection of FECV and indiscernible clinical symptoms of infected cats with FECV at an early stage before the progressive development of FIPV. Title: Isolation and identification of feline calicivirus and feline herpesvirus in Southern Brazil", "Passage: The nasal, oral and conjunctival vias are the natural routes of infection for FCV and FHV-1 . Transmission occurs mainly through direct contact between infected and susceptible cats; however, indirect transmission can also occur in the case of FCV, particularly within a cattery where secretions may contaminate cages, feeding and cleaning utensils or personnel . Reports from cats with URTD have revealed a prevalence ranging among 20-53% for FCV and 10-34% for FHV-1 . In the general healthy cat population from several European countries, USA and Korea, the prevalence of FCV has varied from 15% to 31% whereas values ranging Title: Prevalence of feline immunodeficiency virus and feline leukaemia virus in domestic cats in Hungary", "Passage: The point-of-care tests used in this study detect the presence of FeLV p27 antigen and FIV antibodies against p24 antigen . 38, 39 Sensitivity and specificity values were given according to data provided by Zoetis , although slightly different values can be found in some field studies . 40 One drop of EDTA-anticoagulated whole blood was used as per the manufacturer's instructions . Title: Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection\nPassage: FHV, FPV, FCoV, FIV, hemotropic mycoplasma and presence of FeLV by RT-PCR/PCR as described . The culture was consistently free of the unwanted contaminants. The cat sera were titrated at 4-fold dilutions from 1:4 to 1:256. Samples showing a minimal titre of 1:4 were considered to be FOCMA positive. In addition, samples from week \u00c03 and week 20 p.i. were examined for the presence of antibodies to FeLV gp70, p27 and p15 by Western blot analysis as described .", "Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: Text: A resurgence of pertussis across age groups has occurred in several countries in recent years . Middle-and high-income countries that use an acellular pertussis vaccine for the primary vaccination series have been particularly affected , and infants and adolescents have experienced the greatest increase . Factors that may contribute to the increased risk of pertussis include rapidly waning immunity from those vaccinated with acellular vaccines , asymptomatic transmission from individuals vaccinated with acellular vaccines , genetic adaption of Bordetella pertussis , vaccination delay or refusal , improved surveillance and laboratory capabilities , and overall increased awareness of the continuing Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: There has been an increase in the incidence of pertussis in the European Union from 2011 onwards . The resurgence of pertussis observed in recent years seems to be a complex but real phenomenon due to a number of reasons, including the use of acellular pertussis vaccines in many locales. Lack of mucosal immune responses after aP vaccine administration favour infection, persistent colonization and transmission of the pathogen. Moreover, earlier waning of protective immunity and the circulation of B. pertussis variants depleted of vaccine-included antigens further favor the increase in pertussis disease . Studies in immunized children have reported that Title: Vaccination against Paediatric Respiratory Pathogens\nPassage: antibody responses and protective immunity wane 3-5 years after immunization with acellular pertussis vaccines, which may reflect poor induction of memory T and/or B cells . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Another etiology is pertussis. In the last decade there has also been a resurgence in pertussis cases, especially in highincome countries . Because pertussis immunity after acellular pertussis vaccination is less long-lasting than immunity after wild-type infection or whole-cell vaccination, many women of child-bearing age have waning pertussis antibody levels. Their infants might therefore be born with low transplacental anti-pertussis immunoglobulin G levels, making them susceptible to pertussis infection before completion of the primary vaccination series . In 2014, more than 40,000 pertussis cases were reported to the Centers for Disease Control and Prevention in the United States; in some", "Title: Viral vector-based influenza vaccines\nPassage: Alphaviruses are single-stranded RNA viruses with a positive sense genome of the Togaviridae family. Several alphaviruses are being developed as vaccine vectors, including semliki forest virus , sindbis virus and Venezuelan equine encephalitis . These vectors often are replication deficient replicons that do not encode viral structural proteins, as these regions of the genome are replaced by transgenes of interest. Viral RNAs are self-replicating and are capable of transgene expression at high levels. 98 As an added advantage, when using alphavirus replicons pre-existing immunity to the vector should not pose a problem and multiple sequential vaccinations are a possibility. Furthermore, Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Alphaviruses are positive-sense, single-stranded RNA viruses of the Togaviridae family. A variety of alphaviruses have been developed as vaccine vectors, including Semliki Forest virus , Sindbis virus, Venezuelan equine encephalitis virus, as well as chimeric viruses incorporating portions of SIN and VEE viruses. The replication defective vaccines or replicons do not encode viral structural proteins, having these portions of the genome replaces with transgenic material. Title: Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity", "Passage: for VSRs 26, 27 . Alphaviruses are member of arboviruses containing 27 recognised members 28 with a very wide geographic distribution and several geographical variants on the basis of which they have been classified as Old World and New World viruses 29 . Grouped into seven complexes based on serological cross-reactivity, they infect a variety of host including birds, fishes, mammals including humans and are maintained in natural cycles by transmission between susceptible vectors and vertebrate hosts 30 . Alphaviruses have a single plus-stranded RNA genome encapsulated by capsid proteins. The approx. 12 kb genome consists of two open reading Title: Viral vector-based influenza vaccines", "Passage: Another alphaherpesvirus of poultry, turkey herpesvirus has also been extensively studied as influenza vaccine vector in chickens. HVT encoding the HA gene of an A virus afforded protection from infection with various A viruses. Similarly, a recombinant HVT-H7 vaccine protected chickens against infection with the homologous A virus. 125 Since chickens are often vaccinated at very young age , maternal antibodies against the vector or against the protein encoded by the transgene could influence vaccine efficacy. Interestingly, HVT was shown to be immunogenic even in the presence of these maternal antibodies. 126 Marek's disease virus , an alphaherpesvirus closely related", "Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury\nPassage: Hepcidin is a \u03b2-defensin-like antimicrobial peptide that is mainly produced by the liver. Hepcidin not only shows antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and yeasts, but also functions as a principal iron regulatory hormone . Hepcidin binds to the iron export protein ferroportin and induces its internalization and degradation, which leads to decreased cellular iron export and increased intracellular iron retention . Because iron is an essential nutrient for all organisms, hepcidin also restricts the iron available to invading microbes, thereby enhancing the host defense against pathogens . Furthermore, hepcidin can modulate the lipopolysaccharide -induced acute inflammatory response via Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: washed in phosphate-buffered saline and incubated with a polymer horseradish peroxidase-conjugated secondary antibody for one hour. The sections were further incubated with Dako Liquid DAB Large-Volume Substrate-Chromogen System and counterstained with hematoxylin. Negative controls were included in all assays by replacing the rabbit anti-mouse hepcidin antibody with nonimmune rabbit antiserum. The immunostaining was evaluated using an Olympus BX-50 light microscope . The stain density was analyzed using the Image Pro-Plus 6.0 analysis system , and the level of hepcidin was measured as the integral optical density. Title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia", "Passage: Hepcidin is a low molecular weight, antimicrobial peptide hormone and was first discovered in human urine . It is produced by the liver as a firstline response to inflammatory reactions and high Fe concentrations . Hepcidin plays a fundamental role in the regulation of Fe metabolism , which is a part of foundational cellular functions and thus of vital importance. On the other hand, by participating in redox reactions leading to the production of reactive oxygen species , Fe also causes oxidative stress. Therefore, Fe has been regarded as a potentially toxic element to cells . Fe also plays an Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: Hepcidin is bound to plasma alpha-2 macroglobulin . Evidence suggests that other cells may express the hepcidin mRNA at a much lower level than the hepatocytes; the biological significance of the extra hepatic production of hepcidin remains uncertain. Plasma hepcidin is freely treated through glomeruli and in animals with normal kidney activity it quickly passes through the urine. In addition, a part of hepcidin is cleansed through degradation along with ferritin .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: the surface-exposed N-terminal \u223c12 residues of the pVIII monomer lattice ; the N-terminal N1 and N2 domains of pIII ; and bacterial lipopolysaccharide embedded in the phage coat . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization . Primary antibody responses against the phage appear to be composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: the surface-exposed N-terminal \u223c12 residues of the pVIII monomer lattice ; the N-terminal N1 and N2 domains of pIII ; and bacterial lipopolysaccharide embedded in the phage coat . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization . Primary antibody responses against the phage appear to be composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: antibody responses are composed primarily of IgG1 and IgG2b isotypes, with a lesser contribution of IgG2c and IgG3 isotypes . Deletion of the surface-exposed N1 and N2 domains of pIII produces a truncated form of this protein that does not elicit antibodies, but also results in a non-infective phage particle with lower overall immunogenicity . Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: antibody responses are composed primarily of IgG1 and IgG2b isotypes, with a lesser contribution of IgG2c and IgG3 isotypes . Deletion of the surface-exposed N1 and N2 domains of pIII produces a truncated form of this protein that does not elicit antibodies, but also results in a non-infective phage particle with lower overall immunogenicity .", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: CDC Summary 21 MAR 2020,", "Passage: COVID-19 is caused by a coronavirus. Coronaviruses are a large family of viruses that are common in people and many different species of animals, including camels, cattle, cats, and bats. Rarely, animal coronaviruses can infect people and then spread between people such as with MERS-CoV, SARS-CoV, and now with this new virus . Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Text: Coronaviruses are spherical, enveloped, and the largest of positive-strand RNA viruses. They have a wide host range, including birds, farm animals, pets, camels, and bats, in which they primarily cause respiratory and gastrointestinal disease. Belonging to the order Nidovirales, family Coronaviridae, and the subfamily Orthocoronaviridae there are four genera of coronaviruses-Alphacoronavirus, Betacoronavirus, Deltacorona virus, and Gammacoronavirus . Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: to the broad antiviral effectiveness of carrageenan, patients will receive in parallel a treatment of concomitant viral infections. Therefore, patients will benefit from a decreased probability to develop complications. In consideration of the complications known to accompany an influenza virus illness this combinational therapy meets an urgent medical need. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: cold symptoms than placebo treated patients in the intention-to-treat population . The anti-influenza activity was shown by subgroup analysis of 49 influenza infected patients who benefited from a 3.3 days faster recovery from symptoms. The use of carrageenan nasal spray was associated with a significant reduction of the influenza viral load in nasal fluids and a significant increase in the number of virus free patients within the treatment period of 7 days. In good accordance Prieschl-Grassauer are co-founders of Marinomed Biotechnologie GmbH. Marinomed Biotechnologie GmbH had a role in study design, data collection and analysis, decision to publish, preparation of Title: Role of Antioxidants and Natural Products in Inflammation", "Passage: These extracts significantly suppressed paw edema by carrageenan in the 2nd hour at 20 mg/kg and by dextran in the 1st hour at 100 mg/kg, after induction with the phlogistic agents. Besides, it has reduced total leukocytes and neutrophils migration at all different doses tested producing maximum effect at 20 mg/kg and also suppressed the concentrations of proinflammatory cytokines and increased the level of the anti-inflammatory cytokine IL-10 in the peritonitis model . is a well-known functional food and Chinese herbal medicine used to treat various inflammation associated diseases. According to Sogo et al. the active compound, delphinidin 3-sambubioside ,", "Title: Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection\nPassage: To measure lung leak, the Evan's blue assay was used. Briefly, mice were injected intravenously with a 0.1% sterile solution of Evan's blue dye 30 min prior to sacrifice. The mouse paws and nose turning blue after injection verified dissemination of the dye visually. Evan's blue was measured in the BAL by measuring absorbance at 620 nm on a spectrophotometer. Title: Novel protein chip for the detection of antibodies against infectious bronchitis virus\nPassage: demonstrated that when the positive serum was diluted 1:1000, the spot still turned blue . . Title: Visible Light-Responsive Platinum-Containing Titania Nanoparticle-Mediated Photocatalysis Induces Nucleotide Insertion, Deletion and Substitution Mutations", "Passage: The blue-white screen was originally developed as a screening technique for rapid and convenient recombinant bacteria detection in vector-based molecular cloning experiments . The method is based on the principle of \u03b1-complementation of the \u03b2-galactosidase gene lacZ; therefore, the plasmid should contain lacZ\u03b1 , whereas the E. coli strain must contain mutated lacZ with a deleted sequence . Here, the plasmid was transformed into competent host E. coli XL1-blue cells , which were then plated on LB agar plates containing 100 \u00b5g/mL ampicillin, 50 g/mL X-gal and 0.1 mM isopropyl \u03b2-D-1-thiogalactopyranoside . These plates were then incubated overnight at 37 Title: Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children\nPassage: are colored red or blue , with color intensity corresponding to fold change. Modules whose expression was not significantly different are shown as points rather than squares to simplify the diagram.", "Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: The ratio of comorbidity was much higher in the H5N1 and H7N9 virus fatalities than in the survivors vs. 8.33% , p = 0.046 for H5N1; 58.6% vs. 34.8% , p < 0.001 for H7N9]. Only two H5N6 survivors were found to have underlying conditions, one of which was pregnancy, while only 22.2% of the H9N2 survivors had comorbidities. In total, the rate of comorbidities in the H7N9 fatality and survivor groups was slightly higher than that of the H5N1 groups . Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses", "Passage: For the H7N9 group, the median number of days from onset to confirmation of infection in the fatality groups was slightly longer than that of survivors vs. 8 days, p = 0.011]; however, the median number of days from onset to outcome vs. 31 days, p < 0.001] and number of hospitalization days vs. 25 days, p < 0.001] in the fatality groups was slightly less than those relating to survivors, respectively . Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses", "Passage: In the H5N1 group, the CFR was statistically significantly higher in the index fatalities than in the secondary fatalities vs. 43.3% , respectively, p < 0.001], as was the number of people with comorbidities vs. 0.0% , respectively, p = 0.043]; however, there were no differences between H7N9 virus index and secondary fatalities in the CFR and underlying diseases . Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: higher than that of secondary cases. Although the reasons for this are not understood, they have been attributed to greater incidences of underlying diseases and poultry exposure history in the index cases.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: As RV, RSV, and IFV were the most frequently studied viruses in chronic airway inflammatory diseases, most of the viruses listed are predominantly these viruses. However, the mechanisms stated here may also be applicable to other viruses but may not be listed as they were not implicated in the context of chronic airway inflammatory diseases exacerbation . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s ; with bacterial infections previously considered as the likely culprit for acute exacerbation . However, with the advent of PCR technology, more viruses were recovered during acute exacerbations events and reports implicating their role emerged in the late 1980s . Rhinovirus and respiratory syncytial virus are the predominant viruses linked to the development and exacerbation of chronic airway inflammatory diseases . Other viruses such as parainfluenza virus , influenza virus and adenovirus have also been implicated in acute Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: subsequently spreads to another . Among those with progressive illness, the median time to death is 11 to 13 days, ranging from five to 27 days . Fever and gastrointestinal symptoms may form a prodrome, after which symptoms decline, only to be followed by a more severe systemic and respiratory syndrome . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: or worse, and secondary bacterial infections have been reported . Disease can progress to acute respiratory distress syndrome and multiorgan system failure . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported . General supportive care is key to managing severe cases . Children under Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia,", "Title: Spread from the Sink to the Patient: In Situ Study Using Green Fluorescent Protein (GFP)-Expressing Escherichia coli To Model Bacterial Dispersion from Hand-Washing Sink-Trap Reservoirs\nPassage: Text: D espite early reports , the premise that hand-wash sink traps can act as reservoirs of bacteria that cause nosocomial infections has been frequently overlooked. There has recently been an alarming increase in sink-related outbreaks worldwide, with many reports establishing an observational link . A sink often operates as an open conduit to wastewater in a patient care area that is often in the same room as the patient. Title: Spread from the Sink to the Patient: In Situ Study Using Green Fluorescent Protein (GFP)-Expressing Escherichia coli To Model Bacterial Dispersion from Hand-Washing Sink-Trap Reservoirs", "Passage: from a P-trap reservoir to a vulnerable hospitalized patient. IMPORTANCE Many recent reports demonstrate that sink drain pipes become colonized with highly consequential multidrug-resistant bacteria, which then results in hospital-acquired infections. However, the mechanism of dispersal of bacteria from the sink to patients has not been fully elucidated. Through establishment of a unique sink gallery, this work found that a staged mode of transmission involving biofilm growth from the lower pipe to the sink strainer and subsequent splatter to the bowl and surrounding area occurs rather than splatter directly from the water in the lower pipe. We have also demonstrated Title: Spread from the Sink to the Patient: In Situ Study Using Green Fluorescent Protein (GFP)-Expressing Escherichia coli To Model Bacterial Dispersion from Hand-Washing Sink-Trap Reservoirs", "Passage: In summary, this work for the first time better models the mechanisms of spread of multidrug-resistant pathogens arising from the sink drain and infecting patients. Droplet dispersion from the P-trap does not happen directly. Rather it is a multistage process: dispersal originates from the strainer and/or the bowl after growth of the biofilm up from the microbial reservoir of the P-trap. We also demonstrate sink-to-sink transmission via a common sanitary pipe. This work could have implications for patient safety, infection control, and interventions as well as the design of future hospital plumbing systems to eliminate this mode of transmission to Title: Spread from the Sink to the Patient: In Situ Study Using Green Fluorescent Protein (GFP)-Expressing Escherichia coli To Model Bacterial Dispersion from Hand-Washing Sink-Trap Reservoirs", "Passage: Health care establishments often invest in desperate interventions to deal with nosocomial outbreaks. The preferred method for addressing most of the environmentrelated transmission is to employ enhanced cleaning using chemical and physical agents . Unfortunately, routine approaches are inefficient in completely eliminating drug-resistant Gammaproteobacteria in an inaccessible microbiologically active area such as a sink trap . The wet, humid, and relatively protected environment in a sink trap favors the formation of rich stable microbial communities . These communities will be exposed to liquids and waste that are discarded in a sink and may include antimicrobials, discarded beverages, soap, presumably pathogenic", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first known MERS human-to-human transmission event was one characterized by acute LRT disease in a healthcare setting in Jordan. In stark contrast, a sero-survey of HCW who were sometimes in close and prolonged contact with the first, fatal MERS-CoV case in 2012 , found none of the HCW had seroconverted four months later, despite an absence of eye protection and variable compliance with required PPE standards . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Text: An email from Dr Ali Mohamed Zaki, an Egyptian virologist working at the Dr Soliman Fakeeh Hospital in Jeddah in the Kingdom of Saudi Arabia announced the first culture of a new coronavirus to the world. The email was published on the website of the professional emerging diseases network on 20 th September 2012 and described the first reported case, a 60 year old man from Bisha in the KSA. This information led to the rapid discovery of a second case of the virus, this time in an ill patient in the United Kingdom, who had been transferred from Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November.", "Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation\nPassage: Many studies have shown that the IFITM family provides cellular resistance to viral infection in vitro, and GWAS identified IFITM3 as a resistance gene for influenza in humans . However, we show here that deletion of IFITM proteins reduces the severity of Th2 inflammation in a mouse asthma model, suggesting an evolutionary balance between conferring cellular viral resistance and susceptibility to allergic disease. This study demonstrates that the IFITM family of proteins should be viewed not only as essential proteins for cellular resistance to viral infection but also as important regulators of CD4 + Th cell differentiation and function. Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation", "Passage: In tissue culture experiments, IFITM proteins enable cells to resist infection by both enveloped and nonenveloped viruses, and several distinct mechanisms have been proposed to explain their ability to increase cellular resistance to different viruses . Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation", "Passage: To explore a possible function for the IFITM family in CD4 + T-cell activation or differentiation, we first measured expression of the Ifitm genes by RNA sequencing from CD4 + T cells for a 24 h time course following in vitro activation with anti-CD3 and anti-CD28 in Th0/Th1/Th2 skewing-conditions . This time-course analysis showed that Ifitm1 was expressed at low levels throughout the time course in all conditions. At the start of the experiment, Ifitm3 was most highly expressed of the three genes, but it was then rapidly downregulated after 4 h in response to the TCR/CD28 stimulus. In contrast, Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation\nPassage: responses were reduced. Thus, the IFITM family seems to provide a negative feedback loop on Th1 differentiation in CD4 + T cells, as they are IFN-inducible proteins, which function to limit Th1 differentiation.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: There are several approaches to avoiding pre-existing vector immunity, such as the use of vectors derived from nonhuman sources, using human viruses of rare serotypes , heterologous prime-boost approaches , homologous reimmunization and removing key neutralizing epitopes on the surface of viral capsid proteins . The inhibitory effect of pre-existing immunity can also be avoided by masking the Ad vector inside dendritic cells . In addition, mucosal vaccination or administration of higher vaccine doses can overcome pre-existing immunity problems . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: be expected to result in a reduction in the antigenicity of the vectored antigen.", "Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model\nPassage: In Southeast Asia, Thailand was affected by HPAI H5N1 early, with the first official report of poultry and human outbreaks on 23 January 2004. By the end of January 2004, 32 provinces throughout the north and several in the south experienced outbreaks in many types of poultry. The disease caused 17 human cases from January 2004 to June 2005 2 . The epidemic peaked during a ''second wave'' with 1 717 outbreaks in poultry. Beginning in early 2004, Thai authorities implemented a control strategy based on the prohibition of vaccination and the use of preemptive culling. Approximately 60 million poultry Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: to extend further across the western part of the central plain of Thailand. In contrast, the extreme south of Thailand appeared to be a high-risk area for chickens, with values of relative risk significantly > 10. On the contrary, some areas were especially low-risk for both chickens and ducks despite the occurrence of outbreaks , as in northeastern Thailand and in the middle part of the peninsula. Northern Thailand had low values of relative risk only for chickens. Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: control as they would enable control measures to be targeted and surveillance in ''high-risk'' areas to be strengthened. The HPAI H5N1 virus is now well established in the poultry population in Asia, where the virus has been able to maintain itself and spread as well as periodically re-emerge. The main pathways that have been identified for the spread of H5N1 are the migration and trade of wild birds and the transport of poultry and poultry products . However, the respective roles of these pathways at the global or national scale are still unclear . The persistence of HPAI H5N1 virus Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: 2004 with 990 000 volunteers conducting door-to-door surveys to check poultry in every house nationwide. From mid-2005, the number of outbreaks in poultry decreased substantially but the occurrence of poultry outbreaks in two provinces of Thailand in late 2008 indicates that the threat of HPAI in Thailand remains present.", "Title: Phleboviruses and the Type I Interferon Response\nPassage: Expression of the transcription factor IRF7 is also enhanced by IFN signaling. While the aforementioned activation of IRF3 leads to an initial wave of type I IFN secretion, including IFN-\u03b2 and IFN-\u03b14, enhanced IRF7 expression and activation generates a second wave of type I IFN production which involves additional IFN-\u03b1 subtypes . Title: Type 1 Interferon Induction of Natural Killer Cell Gamma Interferon Production for Defense during Lymphocytic Choriomeningitis Virus Infection", "Passage: The studies do not exclude possible roles for accessory cytokines in enhancing type 1 IFN induction of IFN-\u2425. Certainly, IL-12 is an activator of STAT4 and a potent inducer of IFN-\u2425 . The cytokine IL-18 can enhance the stimulation of IFN-\u2425 by either type 1 IFNs or IL-12 , and new studies deciphering pathways from different sensors have demonstrated synergism between type 1 IFNs and IL-12 for IFN-\u2425 induction in human cells . The results presented here, however, suggest that there may be a short burst of IFN-\u2425 induced by type 1 IFNs independent of IL-12, and our previous work Title: Phleboviruses and the Type I Interferon Response", "Passage: In addition to direct antiviral effects of ISGs and the positive feedback loop via IRF7, type I IFN signaling also induces the production of a range of cytokines and chemokines, pro-and antiapoptotic factors, and affects multiple other signaling pathways. Through modulation of the differentiation and function of dendritic cells, T cells, natural killer cells, and B cells, type I IFNs shape the antiviral immune response beyond the initial innate immune response . Title: Phleboviruses and the Type I Interferon Response", "Passage: Within the endosomal compartments, Toll-like receptor 3 recognizes viral dsRNA and poly, and signals via the adaptor Toll-interleukin 1 receptor domain-containing adapter-inducing IFN-\u03b2 to activate IRF3, NF-\u03baB, and AP-1, and consequently induce the production of type I IFNs as well as inflammatory cytokines . Further, recognition of single-stranded RNA by TLR7/8 and subsequent signaling via the adaptor myeloid differentiation primary response gene 88 results in the secretion of IFN-\u03b1, particularly by specialized plasmacytoid dendritic cells .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: current limitations of influenza vaccines. Title: Viral vector-based influenza vaccines\nPassage: Although currently available influenza vaccines are effective in reducing morbidity and mortality caused by seasonal influenza viruses, they have several limitations. Mainly, continuous antigenic drift of seasonal influenza viruses complicates the production of effective vaccines. The vaccine strains need to be updated almost annually in order to achieve a good antigenic match with the epidemic virus strains. If the vaccine strains do not antigenically match the circulating strains, vaccine efficacy is reduced considerably, as was the case in the 2014-2015 influenza season. Furthermore, the seasonal influenza vaccines will afford little or no protection against antigenically distinct pandemic influenza viruses, which Title: Improved Global Capacity for Influenza Surveillance", "Passage: Influenza viruses are constantly changing, requiring updates to the vaccine each year on the basis of which influenza viruses are infecting persons around the world, how those viruses are spreading, and how well the previous season's vaccine protects against those viruses. Therefore, the increase in the number of countries submitting specimens for seasonal vaccine strain selection is critical for selecting the most representative strains currently circulating. Title: Confronting Potential Influenza A (H5N1) Pandemic with Better Vaccines\nPassage: world's 6.5 billion people. Clearly, dose-sparing formulations are urgently needed.", "Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020\nPassage: was m = 63.1 million per year in 2017 , of which 100q = 2.1% were from Wuhan , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel. As we already know from elsewhere , given the observed cumulative count of c exported cases, we have a balance equation of the cumulative risk of infection: Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "Passage: Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London on their own homepage on 22 January 2020 that estimated the incidence based on three importation events at 4000 cases . Possible reasons for the slight difference include the number of travelers in the previous study was derived from airline passenger data and the assumed length of T was different. Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases as of 17 January 2020 and a University of Hong Kong group estimated 1343 Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: Wuhan was about 11 million at the end of 2018 , the rate of people traveling out from Wuhan City would be 0.018 per day. However, we assumed that the normal population mobility before January 1 was 0.1 times as that after January 10. Therefore, we set the rate of people moving into and moving out from Wuhan City as 0.0018 per day . Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020\nPassage: As of 24 January 2020, the cumulative incidence in China is 830 cases, of which 549 cases were diagnosed in Hubei, 26 in Beijing, 20 in Shanghai, and 53 in Guangdong. Additionally, twenty-six deaths have been linked to the outbreak , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020. Considering that enhanced surveillance has been underway in these importing countries, case ascertainment has been perhaps better in exported case data.", "Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain\nPassage: The 1918-1920 influenza pandemic, or the so-called Spanish flu, was responsible for more than 50 million deaths worldwide . In Europe, the excess mortality rate associated with the 1918-1919 influenza pandemic has been estimated at 1.1%, or approximately an 86% increase in all-cause mortality . This pandemic rapidly spread in a series of pandemic waves that gripped the world beginning in early 1918 . However, according to results of various phylogenetic and molecularclock analyses, the initial circulation of the virus from avian or swine and other mammal species to humans may have occurred a few years earlier . Moreover, the Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: . For instance, estimates of pandemic excess respiratory death rates have ranged from 6.1 per 10,000 for the Canary Islands to 169.7 per 10,000 for Burgos . Moreover, approximately 40% of between-province variation in cumulative excess death rates in Spain during 1918-1919 are explained by spatial factors, such as latitude, population density, and the proportion of children, have explained . However, in few of these analyses did researchers take into account a recrudescent wave in Spain, which peaked in Madrid in late December 1919 and in later months in the rest of Spain . Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: We retrieved all death certificates from the Madrid Civil Registry to construct time series of deaths during the 1918-1920 influenza pandemic . Each record provides specific details of the deceased, including the date of death, age, and causes of death. For years 1917-1920, the registry holds a total of 70,061 death records . Cause-of-death information for each death record allowed us to extract data on deaths attributed to influenza and respiratory causes. Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Spain experienced one of the highest excess mortality rates during the 1918 influenza pandemic in Europe , although this country did not take part in World War I. Perhaps this pandemic outcome is associated with the fact that Spain was going through a demographic transition and experiencing elevated death rates that were only comparable to those of eastern Europe. Of note, the life expectancy in Spain was 41 years in 1910 and 40 years in 1920 .", "Title: Viral factors in influenza pandemic risk assessment\nPassage: our ability to identify truly high-risk prepandemic threats: notably, preparation of seed vaccine stocks for candidate pandemic strains, stockpiling of subtype-specific vaccines, and culling of poultry infected with such strains. Other types of countermeasures, ranging from strengthening local public health departments to stockpiling antivirals or ventilators to developing faster processes for vaccine manufacture to universal vaccines that should be effective against any influenza A strain, should provide benefits whether or not we have advance notice of the strain causing the next pandemic. A comprehensive assessment of priorities to prevent or mitigate the next influenza pandemic should consider the balance between Title: Viral factors in influenza pandemic risk assessment", "Passage: Even with all of the foregoing suggestions in place, it may be improbable that we can reliably identify the 'needle in the haystack' that is the next pandemic influenza strain. Ultimately, the goal is not risk assessment for its own sake, but preparedness and early response to pandemic threats. In other areas where security is at stake, it has been argued that making and improving predictions should be accompanied by a systematic effort to design responses that will not fail even if the predictions are wrong . In the influenza context, the value of some countermeasures is strongly reliant on Title: Viral factors in influenza pandemic risk assessment\nPassage: We conclude with some recommendations for future research and for the practice of pandemic risk assessment. Title: Estimating the Potential Effects of a Vaccine Program Against an Emerging Influenza Pandemic\u2014United States", "Passage: This study highlights several key components to pandemic influenza preparedness, especially for a severe pandemic, including the importance of ensuring readiness to initiate large-scale vaccination programs as early as possible and ideally before the introduction of a novel influenza virus into the United States . Factors that may impact vaccine dose availability include how soon we develop an appropriate vaccine virus candidate, growth characteristics of vaccine virus candidates, influenza vaccine production capacity, efficiency of vaccine allocation and distribution, and vaccine administration capacity. Increased investment and research in vaccine production technologies, including the use of cell-derived recombinant proteins , virus-like particles", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences . N is also reported to interact with actin microfilaments, and the SUMO-1 protein . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in Title: Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment", "Passage: Despite living in different houses and neighborhoods, the tracked individuals showed a high degree of connectivity, with the largest network component accounting for 96.2% of all individuals and 97.8% of all edges . N ij was projected into its constituent affiliation networks: N L and N P . The degree distributions of N L and N P were best fitted by a truncated power-law distribution of the Table 1 . Glossary of network topology terms used in the manuscript. Title: A multidimensional classification of public health activity in Australia\nPassage: other investors; the links to employment and education; and public health investment by, and outcomes in, other sectors such as transport and housing. Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: It has also been observed that the N protein of several coronaviruses can localize in the nucleolus where it may perturb cell cycle activities of the host cell for the benefit of viral mRNA synthesis . IBV N, for example, appears to target CDK2, cyclins A and D1 for proteasomemediated degradation and cause the accumulation of hypophosphorylated retinoblastoma , resulting in the downregulation of CDK1, cyclins E and B1 .", "Title: Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral Restrictions at the Plasma Membrane\nPassage: The use of CCR5 appears to be essential for sexual transmission of HIV-1. Viruses that use CCR5 alone , or more rarely CCR5 and CXCR4 ], predominate in early infection . Individuals homozygous for a 32 base pair deletion in CCR5 that disrupts its expression are largely HIV-1 resistant . X4-using viruses tend to arise later in infection in some, but not all, individuals, and are associated with more rapid progression to AIDS. Whilst they can be transmitted by intravenous drug-use/transfusion, it is not clear why X4 viruses are almost never transmitted sexually given that target CD4+ T cells in Title: Selective use of primate CD4 receptors by HIV-1", "Passage: Next, we wanted to understand more about why blood-derived HIV-1 Env isolates demonstrate this selective use of only some primate CD4 receptors. Thus far, all of the Envs that we have tested are from CCR5-tropic viruses isolated from the blood. There are three types of HIV-1 in the body of an infected person: CCR5 T cell-tropic , CXCR4 T cell-tropic ), and CCR5 macrophage-tropic . Only the first of these transmits to new individuals, whereas the latter two types arise in special evolutionary niches within the human body during the course of chronic infection and rarely transmit . In this Title: Selective use of primate CD4 receptors by HIV-1", "Passage: data file . CCR5, C-C motif chemokine receptor 5; GFP, green fluorescent protein. receptors with early HIV-1 isolates representing each of the four major group M HIV-1 subtypes. These four Envs, isolated from patient blood shortly after initial infection , were pseudotyped onto the Q23\u0394Env-GFP virus, as described before. While human CD4 supported entry of all of these viruses, primate CD4 orthologs supported levels of HIV-1 entry that ranged from 2-to 58-fold lower . Collectively, our study has explored a breadth of HIV-1 isolates taken from patient blood, representing all of the major subtypes found globally, and has found that Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1", "Passage: Beside DC-SIGNR, other HIV-1 receptors are known to influence MTCT of HIV-1 ). Genetic variants in CCR5 have been shown to influence vertical transmission of HIV-1. CCR5 promoter variants resulting in higher expression of the receptor were associated with increased risk of MTCT of HIV-1 among sub-Saharan Africans . The 32-pb deletion polymorphism in CCR5 has be shown to protect from vertical transmission of HIV-1 , but this variant is virtually absent among African populations . High copy numbers of CCL3L1, a potent HIV-1 suppressive ligand for CCR5, are associated with higher chemokine production and lower risk of MTCT of", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: the percentage of confirmed cases among males to be 66%, compared with 34% among females .", "Title: Estimating the number of infections and the impact of non-\nPassage: distance from others. Title: Estimating the number of infections and the impact of non-\nPassage: 15. Nouvellet, P. et al. A simple approach to measure transmissibility and forecast incidence. Title: A statistical method utilizing information of imported cases to estimate the transmissibility for an influenza pandemic", "Passage: Many kinds of data such as sentinel surveillance of influenza-like-illness , serological survey, and syndromic data are able to infer the transmissibility of infectious diseases. Common surveillance data can be fitted into an exponential growth model or Kermack-McKendricktype models to estimate R 0 . Likelihood-based methods are an alternative . Chowell et al. showed that these types of methods are not sensitive on R 0 estimation given an acceptable goodness of fit. Nevertheless, one of the caveats of using ILI surveillance data is the underreporting although several approaches were developed to adjust this problem . Title: A statistical method utilizing information of imported cases to estimate the transmissibility for an influenza pandemic", "Passage: Serological data is another source for inferring transmissibility of an influenza virus . This kind of data helps detecting subclinical infections and the sampling is not affected by the reporting practices. However, it is comparatively costly and requires laboratory resources. A longer time will be taken to ascertain a disease and thus it cannot provide initial estimate for a pandemic outbreak . Seroprevalence surveys are usually suggested to monitor the level of disease spread after a local outbreak in community .", "Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: compounds 8012-0652, C481-1256, and G319-0078 were screened out with potency in the nanomolar range against infection of a panel of hantaviruses, including SNV, ANDV, and HTNV . Further studies should be performed to evaluate the safety and efficacy of these small molecules in vivo. Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: to impaired barrier structure of adherent junctions, which could lead to incremental cellular permeability . It has been demonstrated HTNV or ANDV infection could disrupt the interaction of \u03b23 integrin with VEGFR2 and induce VEGFR2 hyper phosphorylation, which may enhance the permeability of infected endothelial cells by sensitizing them to VEGF . As increased VEGF content has been noted in the plasma of HFRS and HCPS patients and is closely related to disease severity in the acute phase , it is feasible to repurpose those FDA-approved drugs targeting vasoactive mediators for use as hantaviral infection therapy. In line with this Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: are suspected or presumed to have a potent interferon-pathway antagonism mechanism relative to other viruses, a mechanism that acts positively to prevent an effective innate response from forming, at least early in infection . Yet some instances are reported wherein highly pathogenic hantaviruses, such as SNV, are also able to induce expression of interferon-stimulated gene mRNAs, even very early in infection, with ISG proteins, as expected, taking longer to appear in the cell . Anti-interferon activities have also been attributed to the NSs protein that may be elaborated in cells infected by serotypes that encode this protein . Other investigators Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: have examined the activities of hantavirus glycoproteins and other proteins that might themselves directly affect some aspects of the pathogenic progression associated with hantavirus infection of humans, such as vascular permeability changes. While early attempts to directly cause increases in permeability of endothelial monolayers with viral particles or viral infection were largely disappointing, hantaviruses have been identified as adversely affecting endothelial migration over substrata and in potentiating VEG-F-induced endothelial permeability .", "Title: The protective and pathogenic roles of IL-17 in viral infections: friend or foe?\nPassage: Viral infections are common causes of both chronic and acute tissue pathology that create a significant health burden worldwide. For example, human papillomaviruses are the causative agents of epithelial hyperplasia of the skin and genital tract . Persistent infection of HPV can result in malignant lesions, the most common being cervical cancer, which had caused an estimated 0.6 million new cases in 2018 and contributed to more than 0.3 billion deaths . Hepatitis B virus and hepatitis C virus are the major causes of hepatitis and can progress to liver fibrosis, cirrhosis and eventually liver cancer . Human immunodeficiency virus Title: Anxiety and Depression: Linkages with Viral Diseases", "Passage: the specific mechanisms can vary by viral illness. Mental conditions such as major depression can delay help-seeking or reduce the likelihood of detection of other health conditions including communicable diseases. 1 Depression and psychological stress have been shown to have a number of biological effects including reduced cell-mediated immunity and increased inflammatory processes. 3 A further issue is that some viral diseases can directly affect the brain and result in mood disorders or cognitive impairment. 1 Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Another mechanism that viral infections may use to drive acute exacerbations is the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. Infection with a multitude of respiratory viruses causes disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells. For example, IFV infection was found to induce oncostatin M which causes tight junction opening . Similarly, RV and RSV infections usually cause tight junction opening which may also increase the infiltration rate of eosinophils and thus worsening Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Symptoms are common to each infection and manifest on a gradient. Generally, but far from always, influenza infection is more likely to result in a patient feeling so unwell as to take to their bed and have a fever, than RSV, an HRV, CoV or other common cold virus infection, during which daily life is usually less impacted.", "Title: Haunted with and hunting for viruses\nPassage: also been identified in bat with potential severe outcomes. Lyssaviruses in the Rhabdoviridae family have been linked with severe fatal human cases, even in the developed countries, including Australia, with the bites of bats in the city . The potential roles of these viruses in bats for interspecies transmission are yet to be elucidated. Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: Text: Bats have received much attention in recent years for their role as reservoir hosts for emerging viral zoonoses, including rabies and related lyssaviruses, Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS coronavirus . In most non-Chiropteran mammals, henipaviruses, filoviruses, and coronaviruses induce substantial morbidity and mortality, display short durations of infection, and elicit robust, long-term immunity in hosts surviving infection . Bats, by contrast, demonstrate no obvious disease symptoms upon infection with pathogens that are highly virulent in non-volant mammals but may, instead, support viruses as longterm persistent infections, rather than transient, immunizing pathologies . Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: The findings may help to explain why bats are often the source for viruses that are deadly in humans. Learning more about bats' antiviral defenses and how they drive virus evolution may help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. More studies are needed in bats to help these efforts. In the meantime, the experiments highlight the importance of warning people to avoid direct contact with wild bats. up resource supply of infection-susceptible host cells, were first developed for HIV but have since been applied to other chronic infections, including Title: Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses", "Passage: The identification of high neutralizing antibody titers indicates that bats experience infections followed by seroconversion, which in case of humans is correlated with clearance of the virus and survival of infection 48 . CCHFV might thus exemplify another highly pathogenic agent that is effectively controlled in bats.", "Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% of clinical subjects, and 6.7% of community subjects . Coronavirus OC43 was the most common virus detected in community members . A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: We also compared and contrasted the clinical and community results. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses found in the clinical sample. These three infections resulted in 41 viruses detected in 15 subjects clinically, and eight infections detected in five people in the community. Together they infected 94% of clinical subjects, and 7% in the community . The most common virus detected in community samples was Coronavirus OC43; this virus was detected in 13.3% people in the community and not in any of the clinical samples. However a different strain, coronavirus OC 229 Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: viruses in the clinical sample and their prevalence in the community. Finally, some of the viruses detected in this study have not been detected and implicated with ARIs in Nigeria. There is no report, to the best of our knowledge, implicating coronavirus in ARIs in Nigeria, and it was detected in 12 subjects in this study. Although cases of double and triple infections were observed in a study in Nigeria in 2011 , as far as we are aware, reports of quadruple infections are rare and have not been reported in Nigeria previously. Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Abstract: OBJECTIVE: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical surveillance in Nigeria. RESULTS: Children were selected via convenience sampling from communities and a tertiary care center during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority of subjects were under 6 years old, of whom 46 were infected . A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection", "Title: Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review\nPassage: One reviewer screened and evaluated the titles and abstracts. Articles were widely included in a first stage. The full-text review and the final selection of the articles were made by two reviewers. Title: Cochrane Systematic Reviews of Chinese Herbal Medicines: An Overview\nPassage: based on how well the review scored on the first 9 questions. Title: Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude", "Passage: We appreciate the positive comments from the reviewers, who described our results as \"interesting and novel,\" \"engaging,\" \"well written,\" \"clear,\" \"quite intriguing,\" and \"very powerful.\" Further a reviewer noted that the manuscript does a \"good job of convincing me that this approach can be translatable.\" We also thank the Reviewers for their constructive feedback, which we are confident has strengthened the manuscript. We have addressed the comments by collecting additional data, performing additional analyses, and clarifying our conclusions. Below is a point-by-point response to the reviewers comments. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: The health-evidence.ca registry was used to identify gaps and areas of wealth in the public health review literature. Each of the 21 Focus of Review topic areas were searched, and the quantity and proportion of reviews rated methodologically strong, moderate, and weak were identified. Three categories were used to define availability of reviews within each topic area: few, representing 1-150 reviews; moderate, representing 151-300 reviews; and, many, representing topic areas possessing greater than 301 reviews. Reviews that addressed multiple topics were accounted for within each topic area that they addressed .", "Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: Influenza is an infectious disease affecting mainly upper respiratory tract worldwide. Influenza virus causes between three and five million severe cases and an estimated 250,000-350,000 deaths annually. In the European Union, there are between 40,000 and 220,000 annual deaths attributable to influenza. However, mortality is only the tip of the iceberg in terms of the disease burden, since influenza also causes a decrease in functional status and increased dependency in the elderly . Estimating the burden of disease caused by influenza is difficult because many cases do not require medical care, or no confirmatory laboratory tests are widely performed to Title: Use of daily Internet search query data improves real-time projections of influenza epidemics", "Passage: Seasonal influenza remains an important infectious cause of morbidity and mortality . In the USA alone, estimates of annual incidence range from 9.2 million to 35.6 million cases, resulting in 140 000 to 710 000 hospitalizations and 12 000 to 56 000 deaths . Title: Forecasting the 2013\u20132014 Influenza Season Using Wikipedia\nPassage: hospitalized from seasonal influenza complications, and 3,000-49,000 people die each year . The result is a significant public health and economic burden for the U.S. population . Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: According to World Health Organization statistics, influenza occurs globally with an estimated annual attack rate of 5%-10% in adults and 20%-30% in children . These annual epidemics are estimated to result in approximately 3 to 5 million cases of severe illness worldwide and around 250 000 to 500 000 deaths, which is a major cause of losses in human lives and a grave global public health issue.", "Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: Clinical investigation found that high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, suggesting that cytokine storm was associated with disease severity 12 . Other than its direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors. Therefore, in COVID-19 patients, HCQ may also contribute to attenuating the inflammatory response. In conclusion, our results show that HCQ can efficiently inhibit SARS-CoV-2 infection in vitro. In combination with its anti-inflammatory function, we Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: different expression levels of virus nucleoprotein at the indicated drug concentrations at 48 h p.i. . Taken together, the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs. Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: well as over 10,566 confirmed cases in 72 other countries. Such huge numbers of infected and dead people call for an urgent demand of effective, available, and affordable drugs to control and diminish the epidemic. Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: To this end, we evaluated the antiviral effect of HCQ against SARS-CoV-2 infection in comparison to CQ in vitro. First, the cytotoxicity of HCQ and CQ in African green monkey kidney VeroE6 cells was measured by standard CCK8 assay, and the result showed \u00a9 The Author 2020", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: Finally, rVSV-G and rVSV-EBOV trials on PaKiT01 cells were best fit by models assuming constitutive immunity, while rVSV-MARV infections on PaKiT01 were matched equivalently by models assuming either induced or constitutive immunity-with induced models favored over constitutive in AIC comparisons because one fewer parameter was estimated . For all virus infections, PaKiT01 cell lines yielded b estimates a full order of magnitude higher than Vero or RoNi/7.1 cells, with each b balanced by an immune response also an order of magnitude higher than that recovered for the other cell lines . As in RoNi/7.1 cells, PaKiT01 parameter fits localized in Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: Because and \" both contribute to this initial antiviral rate, induced and constitutive immune assumptions are capable of yielding equally rapid rates, depending on parameter fits. Indeed, under fully induced immune assumptions, the induced antiviral acquisition rate estimated for rVSV-MARV infection on PaKiT01 cells was so high that the initial antiviral rate exceeded even that estimated under constitutive assumptions for this cell-virus combination . In reality, we know that NPC1 receptor incompatibilities make PaKiT01 cell lines constitutively refractory to rVSV-MARV infection and that PaKiT01 cells also constitutively express the antiviral cytokine, IFN-a. Model fitting results suggest that this constitutive expression Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: of these viruses, rVSV-EBOV and rVSV-MARV, are recombinants for which cell entry is mediated by the glycoprotein of the bat-evolved filoviruses, Ebola and Marburg , thus allowing us to modulate the extent of structural, as well as immunological, antiviral defense at play in each infection. Previous work in this lab has demonstrated incompatibilities in the NPC1 filovirus receptor which render PaKiT01 cells refractory to infection with rVSV-MARV , making them structurally antiviral, over and above their constitutive expression of IFN-a. All three cell lines were challenged with all three viruses at two multiplicities of infection : 0.001 and 0.0001. Between Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: Total monolayer destruction occurred in all cell-virus combinations excepting rVSV-EBOV infections on RoNi/7.1 cells and rVSV-EBOV and rVSV-MARV infections on PaKiT01 cells. Monolayer destruction corresponded to susceptible cell depletion and epidemic turnover where R-effective was reduced below one . For rVSV-EBOV infections on RoNi/7.1, induced antiviral cells safeguarded remnant live cells, which birthed new susceptible cells late in the time series. In rVSV-EBOV and rVSV-MARV infections on PaKiT01 cells, this antiviral protection halted the epidemic before susceptibles fully declined. In the case of rVSV-EBOV on PaKiT01, the birth of new susceptibles from remnant live cells protected by antiviral status maintained", "Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Multiple, patchy, sub-segmental or segmental groundglass density shadows in both lungs. They were classified as \"paving stone-like\" changes by fine-grid or small honeycomb-like thickening of interlobular septa. The thinner the CT scan layers, the clearer the ground-glass opacity and thickening of interlobular septa were displayed. A slightly high-density and ground-glass change with fuzzy edge in the fine-grid or small honeycomb-like thickening of interlobular septa were presented by the high-resolution computed tomography , . The resolution of X-ray was worse lower than that of CT in the resolution, which was basically manifested as ground-glass When coughing or sneezing, it is Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Atypical CT/X-ray imaging manifestation, including Single, or multiple, or extensive subpleural grid-like or honeycomb-like thickening of interlobular septum, thickening of the bronchial wall, and tortuous and thick strand-like opacity. Several patchy consolidations, occasionally with a small amount pleural effusion or enlargement of mediastinal lymph nodes, can be seen . This is mostly seen in the elderly. Title: Tidal changes on CT and progression of ARDS", "Passage: Images were reconstructed to voxel size of 0.98*0.98*1 mm with standard Filtered Back Projection FBP. The dosage for each scan was 9 1.4 mSv. For the current study, inspiratory and expiratory images were registered, manually segmented by trained operators, and replotted in PRM using the same methodology used for the animal scans. High risk and severely injured voxels were identified and measured using the inspiratory-expiratory density ranges derived from the animal experiments. In addition to PRM analysis, CT density analysis was performed, using methods described in the original publication. Briefly, three dimensional regions of interest were segmented on the original Title: Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection", "Passage: All radiographic examinations were performed using digital radiographic equipment and a standardized technique . Thin-section CTs of the thorax were performed using a 16 channel CT scanner , with the following parameters: 1.25 mm slice thickness with a 2.5 mm gap, supine position, scanning during inspiration, 6 seconds scan time, 120kV, auto mA.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: doses, respectively, and was maintained in 79% participants up to study end at week 60. Neutralising antibodies were detected in 50% participants at one or more time points during the study, but only 3% maintained neutralisation activity to end of study. T-cell responses were detected in 71% and 76% participants after 2 and 3 doses, respectively. There were no differences in immune responses between dose groups after 6 weeks and vaccine-induced humoral and cellular responses were respectively detected in 77% and 64% participants at week 60. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Serological testing such as ELISA, IIFT and neutralization tests are effective in determining the extent of infection, including estimating asymptomatic and attack rate. Compared to the detection of viral genome through molecular methods, serological testing detects antibodies and antigens. There would be a lag period as antibodies specifically targeting the virus would normally appear between 14 and 28 days after the illness onset . Furthermore, studies suggest that low antibody titers in the second week or delayed antibody production could be associated with mortality with a high viral load. Hence, serological diagnoses are likely used when nucleic amplification tests are Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection", "Passage: Antibodies were tested at 10 \u00b5g/ml and threefold serial dilutions until a nonbinding concentration was determined. Each antibody was tested in at least two replicates for specificity and affinity estimations. Note that only 14 of 15 HA-binding antibodies have curves in G because one of the HA-reactive antibodies only binds HA on whole virions, not on the recombinant protein. Title: Generation and comparative genomics of synthetic dengue viruses\nPassage: titers from serum taken 14 dpi . Note that there were not sufficient quantities of serum for 5 samples: 2 from group 1, 1 from group 2 and 2 from control group for quantification of neutralizing Ab detection . Despite the lower rate of detection of viral RNA in these samples, the mean viral RNA level in this group was significantly elevated as compared with controls. No viral RNA was detected in the serum of sham-infected mice.", "Title: HBV Immune-Therapy: From Molecular Mechanisms to Clinical Applications\nPassage: First reported in chronic Lymphocytic Choriomeningitis Virus infection, the up-regulation of co-inhibitory receptors, or immune checkpoints, has then been widely described as a common hallmark of exhausted CD8 T cells in different chronic infection and tumor models. Indeed, gene expression profiling and functional T cell analysis of virus-specific CD8 T cells from chronically LCMV-infected mice led to the characterization of the role played by PD-1 and other highly co-expressed inhibitory molecules, such as 2B4, CTLA-4, Tim-3, Lag-3, TIGIT, BTLA, CD160, PSGL1, in promoting a dysfunctional phenotype in exhausted antigen-specific CD8 T cells . Later on, the evidence that an efficient Title: The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection", "Passage: Furthermore, Nef inhibits T cell receptor induced lymphocyte activation . These strategies contribute to the suppression of HIV proliferation in the lymph nodes, and also inhibit the propagation of infection. Other immunosuppressive mechanisms used by HIV have also been reported. Cosuppressive molecules, such as B7-H1 on DCs and PD1 on T lymphocytes, are upregulated in patients with HIV, and induce apoptosis through their interaction with DCs and T lymphocytes. In addition, HIV is thought to induce regulatory T cells . Title: Confounding roles for type I interferons during bacterial and viral pathogenesis", "Passage: Several hallmarks of the negative effects of chronic viral infection have been discovered using this system. Mice become chronically infected with LCMV because of T-cell 'exhaustion' that prevents normal clearance . Several factors have been implicated in the suppression of T-cellmediated clearance of chronic LCMV; most salient among them are IL-10 and PD-1 . IL-10 is known to antagonize inflammatory activation on multiple immune cell types and its neutralization prevents chronic infection with LCMV . PD-1, a member of the CD28/CTLA4 family of T-cell regulators, is upregulated on exhausted T cells found in chronically infected mice. Its ligands, PD-1L and Title: Tumor Restrictions to Oncolytic Virus", "Passage: On a cellular level, virus replication is controlled by antiviral defense molecules , which in turn are primarily controlled by type I IFN signaling. In addition to classical type I IFN-or cytokine-induced antiviral signaling, tumors may employ other antiviral defense mechanisms. For example, stromal cells may secrete peptides with antiviral properties called defensins . The defensins are amphiphatic and typically 29-42 amino acids in length and interfere with viruses by physically binding to and disrupting virus particles and/or by inducing antiviral responses in target cells via pattern recognition receptors. At least oral squamous cell carcinomas were found to overexpress defensins", "Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells\nPassage: Amino-acid sequence alignment of IFITM5, IFITM1, IFITM2, and IFITM3 derived from mice. The conserved residues are highlighted in black. The three conserved cysteines are highlighted in red and numbered based on the sequence of IFITM5 and IFITM3 . The residues unique in IFITM5 are highlighted in gray. The first and the second transmembrane domains, the extracellular sequences, and the cytoplasmic loop are indicated by arrows and denoted as TM1 and TM2, EC, and the CP loop, respectively. The TM domains were predicted by SOSUI. The aspartates at the C-terminal region in IFITM5 are shown in blue. B) The schematic illustration Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: Amino-acid sequence alignment of IFITM5, IFITM1, IFITM2, and IFITM3 derived from mice. The conserved residues are highlighted in black. The three conserved cysteines are highlighted in red and numbered based on the sequence of IFITM5 and IFITM3 . The residues unique in IFITM5 are highlighted in gray. The first and the second transmembrane domains, the extracellular sequences, and the cytoplasmic loop are indicated by arrows and denoted as TM1 and TM2, EC, and the CP loop, respectively. The TM domains were predicted by SOSUI. The aspartates at the C-terminal region in IFITM5 are shown in blue. B) The schematic illustration Title: Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates", "Passage: IFITM family members contain a conservative CD225 domain and two terminal hypervariable regions . The CD225 domain accounts for more than half of the protein in length, containing one intact transmembrane domain , two S-palmitoylation sites regions and partial TMD in the C-terminus of the protein. The S-palmitoylation sites have been demonstrated to play important roles in post-translational processing and stability of IFITM proteins . The N-terminal hypervariable region generally contains 21 amino acid residues and the C-terminal one includes a TMD . Title: Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells", "Passage: As described above in the Introduction, cysteine residues are the substrate for S-palmitoylation. IFITM5 possesses three cysteines, Cys52 and Cys53 in the TM1 domain, and Cys86 in the CP loop . All of these cysteines are highly conserved among the mammalian IFITM family proteins . To identify the modification site in IFITM5, we prepared cysteine-substituted mutants, IFITM5-C52A/C53A, -C86A, and -C52A/C53A/C86A . The osteoblast cells harboring each plasmid were cultured in the absence of 2BP, and then the cell lysate was extracted. Figure 3 -B shows the results of the western blot detecting the expression of all the mutants in the", "Title: Targeting cancer stem cell pathways for cancer therapy\nPassage: Additionally, there are other ways to separate CSCs from tumors. In 1996, Dr. Goodell observed that after adding Hoechst 33342 to a culture of bone marrow cells, a few cells did not accumulate dyes, and he claimed that these few cells were side population cells. Therefore, SP cells can be separated by fluorescence screening after the outflow of Hoechst 33342. Recently, SP cells have been identified in various normal tissues and tumor cells. SP cells have high homology, self-renewal and multidirectional differentiation potential. 47,48 Some reports have shown that ABCG2 is highly expressed in SP cells. 47,49 ABCG2 is highly Title: Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells", "Passage: and are responsible for tumor maintenance and metastasis . Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the ''side population '' . Ho and colleagues isolated and characterized SP cells from six human lung cancer cell lines and showed that an elevated expression of ABCG2 as well as other ATP-binding cassette transporters were positively correlated with resistance to multiple chemotherapeutic drugs . In addition, Gutova and colleagues have purified uPAR-positive CSCs from three lung cancer cell lines. These uPAR-positive cells co-expressed with CD44 and MDR1, and had the ability to Title: Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells", "Passage: For cell surface marker identification, a single cell suspension of sixth-to eighth-passage cells from trypsinized spheres was stained with anti-CD133, CD117 , or ABCG2 and secondary fluorescein -or phycoerythrin -coupled antibodies . Cells were fixed with 2% paraformaldehyde and were analyzed with a BD FACSCalibur apparatus . Title: Building Cell Selectivity into CPP-Mediated Strategies\nPassage: . Identification of a peptide that selectively enters colon cancer cells is very promising for developing new colon cancer diagnostic tools and therapeutic agents, such as RPMrel-D 2 . Colorectal cancer causes 655,000 deaths worldwide per year, and it is the third most common form of cancer and the third leading cause of cancer-related death in the western world. RPMrel could lead to the development of new direct targeting agents to fight against this disease.", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: hospitalization, and ultimately die. 22 Early predictions for incubation time are between 2 and 14 days, based on data from similar coronaviruses. The 14-day criterion for epidemiological risk assumes the longest estimated incubation time. 23 In addition, the World Health Organization has created its own interim case definition. 24 Title: Quantifying social distancing arising from pandemic influenza\nPassage: We do not observe i and must infer it from the daily death and/or hospitalization data. In the case of deaths ), we must account for the time delay between infection and death. The time from symptom onset to death was remarkably similar across all age groups with a mode of 7 days . We add 1.5 days for the incubation period and round to the nearest integer, so that tZ9. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: a) The mean incubation period was 5.2 days : 4.1-7.0) . We set the same value of the incubation period and the latent period in this study. Thus, \u03c9 P = \u03c9' P = 0.1923. b) There is a mean 5-day delay from symptom onset to detection/hospitalization of a case . The duration from illness onset to first medical visit for the 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days . In our model, we set the infectious period of the cases as 5.8 days. Therefore, \u03b3 P = 0.1724. c) Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: One of the critical issues in infectious disease epidemiology is that the time of infection event is seldom directly observable. For this reason, the time of infection needs to be statistically estimated, employing a backcalculation method . Using a sophisticated statistical model with doubly intervalcensored likelihood and right truncation with an exponential growth of cases, the mean incubation period has been estimated to be about 5.0 days . To understand the time-dependent risk of infection throughout the course of outbreak and estimate the effectiveness of the quarantine measure from 5 to 19 February 2020, I aimed to estimate the incidence", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The general types of influenza vaccines available in the United States are trivalent inactivated influenza vaccine , quadrivalent influenza vaccine , and live attenuated influenza vaccine . There are three types of inactivated vaccines that include whole virus inactivated, split virus inactivated, and subunit vaccines. In split virus vaccines, the virus is disrupted by a detergent. In subunit vaccines, HA and NA have been further purified by removal of other viral components. TIV is administered intramuscularly and contains three or four inactivated viruses, i.e., two type A strains and one or two type B strains. TIV efficacy is measured by Title: Current and Novel Approaches in Influenza Management", "Passage: Three types of vaccines against influenza are currently used worldwide including inactivated influenza vaccine , live-attenuated influenza vaccine and influenza virus subunit vaccine: each of which has its own advantages and drawbacks. IIV is formulated with replication-incompetent virus, due to whole pathogen inactivation usually achieved by formaldehyde treatment or split virion vaccines generated by disruption of the viral membrane . Intramuscular administration of the IIV has been shown to induce both local and systemic immunity . However, to maintain the antibody titers, booster vaccinations are required. Additional considerations on the vaccine efficacy were raised following metadata analysis suggesting only 40% Title: Virus-Vectored Influenza Virus Vaccines", "Passage: serotypes such as adenovirus types 3, 7, 11, and 35 can evade anti-Ad5 immune responses while maintaining effective antigen delivery and immunogenicity . Prime-boost strategies, using DNA or protein immunization in conjunction with an adenovirus vaccine booster immunization have also been explored as a means to avoided preexisting immunity . Title: Viral vector-based influenza vaccines", "Passage: Several different vaccine formulations are available: trivalent or quadrivalent inactivated virus vaccines or live attenuated influenza virus vaccines . Most vaccines are produced in embryonated chicken eggs, but vaccines produced in mammalian or insect cells are also available. Inactivated vaccines are administered intramuscularly or sometimes intradermally and predominantly aim at the induction of serum antibody responses against the viral hemagglutinin and neuraminidase to a lesser extent. Protection from disease is mainly mediated by virus neutralizing antibodies against HA, but NA-specific antibodies also contribute to protective immunity. 1 Currently licensed LAIV are administered locally via nasal spray. Viruses are attenuated by", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: Koch recognized as early as 1891 that associating the presence of a certain agent with a certain disease is complex, and he therefore postulated guidelines that should be followed before an agent can be classified as a pathogen . His postulates can be summarized in three points: The microbe occurs in every case of the disease in question and under circumstances which can account for the pathological changes and clinical course of the disease; the microbe occurs in no other disease as a fortuitous and nonpathogenic parasite; and , after being fully isolated from the body and repeatedly grown in Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond", "Passage: been made to adjust the Koch's postulates specifically for viruses and the current methodologies deployed , fulfilling these postulates is still not feasible on most occasions due to the lack of an efficient cell culture system, difficulties in antigen synthesis and high levels of viral genetic diversity within viral groups, reviewed in the literature . Title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus\nPassage: for the new disease syndrome were unsuccessful, leading to the disease being temporarily designated mystery swine disease in North America. Koch's postulates for MSD were fulfilled in 1991 with a previously unidentified RNA virus discovered in Europe, named Lelystad virus . The discovery was quickly followed by isolation of the virus, initially referred to as swine infertility and respiratory syndrome virus or SIRS virus, in North America . Title: The social benefits of private infectious disease-risk mitigation", "Passage: The first two axioms imply that P is a matrix of conditional probabilities, and the third implies that it is symmetric.", "Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic\nPassage: infections for both of these two strains during some parts of that half year and 1 ). Although we note that a much larger study period than our data allows would likely offer more insights. 5 . It has been proposed that, due to school/business closure due to traditional lunar New Year holidays in Taiwan that falls typically between week 4 to week 8 of each year, more frequent contacts in the households among family members who spent more time at home during the holidays tends to result in increased transmission . It is interesting to note that during 2008-2014, Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: shown that excess influenza deaths during these months similar to those in the temperate zones can also observed in Taiwan . It has also been proposed previously that Taiwan is an evolutionarily leading region for global circulation of influenza virus A . Moreover, past studies on sequence comparison of seasonal influenza strains A in Taiwan versus vaccine strains have showed that many vaccine-like Taiwanese strains in 1995-2003 were circulating at least 2 years before the vaccine strains were introduced . Hence investigating circulation patterns of seasonal influenza virus strains might shed lights on possible global circulation patterns in the following Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: When there is more than one wave of infections, as in our current study, a variation of the Richards model can be utilized, which makes the distinction between two types of turning points ; one type which occurs at the peak incidence, and a second type which occurs in a multi-wave epidemic when the growth rate of the cumulative case number begins to increase again, indicating the beginning of the next wave. Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: This data issue is even more glaring during summers, when there are typically less clinical cases and hence less number of samples being collected for laboratory testing. During the second half of 2012, no significant wave can be detected via the Richards model. However, we note that most of the samples tested during that time was determined to be H3N2 , although the typically low weekly number of samples being tested during summer, due to more mild and subclinical cases in summers, became an obstacle for good model fitting. Nevertheless, the study, designed to qualitatively compare the temporal patterns and", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The VEE replicon systems are particularly appealing as the VEE targets antigen-presenting cells in the lymphatic tissues, priming rapid and robust immune responses . VEE replicon systems can induce robust mucosal immune responses through intranasal or subcutaneous immunization , and subcutaneous immunization with virus-like replicon particles expressing HA-induced antigen-specific systemic IgG and fecal IgA antibodies . VRPs derived from VEE virus have been developed as candidate vaccines for cytomegalovirus . A phase I clinical trial with the CMV VRP showed the vaccine was immunogenic, inducing CMV-neutralizing antibody responses and potent T cell responses. Moreover, the vaccine was well tolerated and Title: Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice", "Passage: Venezuelan equine encephalitis virus replicon , lacks its structural protein genes and expresses green fluorescent protein under its subgenomic promoter. Transformed Escherichia coli containing the WNV and VEE replicon plasmids were grown at 37\u02daC. E. coli stocks containing the packaging vector were grown at 25\u02daC. WNV, VEE, and Semliki Forest virus replicon plasmids were linearized with Xba1, Not1, or Spe1 , respectively. RNA was in vitro transcribed using mMESSAGE mMACHINE mRNA kit according to the manufacturer's instructions. Title: Viral vector-based influenza vaccines", "Passage: VEE is an appealing vaccine vector, as it was previously shown that VEE mainly targets antigen-presenting cells in the lymphoid tissues and therefore primes rapid and robust immune responses. 103 SIN, SFV and VEE have all been tested as influenza vaccine vectors . An SFV vaccine expressing the HA and NP genes could protect mice from infection with A virus; 99 the same held true for a SIN replicon expressing either the HA gene or an immunodominant CD8 C T-cell NP epitope. 104, 105 VEE was more extensively evaluated as an influenza vaccine vector, VEE-H1 vaccination protected mice from infection Title: Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice", "Passage: experimental procedure, allowing for more efficient optimization of other parameters, we used FlyFectin in subsequent experiments at an RNA to reagent ratio of 1 \u03bcg RNA to 4 \u03bcL FlyFectin. Transfection efficiency for these parameters was quantified using a VEE replicon RNA that expresses high levels of GFP under the subgenomic promoter. Both VEE and WNV efficiently replicate in C6/36 cells . The VEE system was used because it is more specific and sensitive than using an antibody to detect cells transfected with WNV replicon in C6/36 cells, which are highly autofluorescent. The percentage of GFP-positive cells was determined by", "Title: The NLRP3 Inflammasome and IL-1\u03b2 Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis\nPassage: Viral fulminant hepatitis is a clinical syndrome characterized by massive necrosis of hepatocytes along with hepatic encephalopathy during the infections . Despite advances in the development of antiviral drugs, a poor understanding of the immune mechanisms underlying viral FH has largely stalled the identification of effective clinical interventions. Fortunately, the recent development of an animal model of FH using murine hepatitis virus strain-3 infection has provided insights in understanding the pathogenesis and developing novel therapeutics for the disease . Title: Inherited IL-18BP deficiency in human fulminant viral hepatitis", "Passage: Hepatitis A virus , hepatitis B virus , hepatitis C virus , and hepatitis E virus are the most common liver-tropic viruses in humans. HAV and HEV typically cause an acute form of hepatitis, whereas HBV and HCV frequently cause chronic hepatitis, increasing the risk of cirrhosis and hepatocellular carcinoma . HEV may also cause chronic infection . In rare cases, primary infections with these viruses, particularly for HAV, HBV, and HEV, can lead to fulminant viral hepatitis . FVH is defined as severe liver destruction in the absence of preexisting liver disease, leading to encephalopathy within 8 wk of Title: Inherited IL-18BP deficiency in human fulminant viral hepatitis\nPassage: in the absence of liver transplantation. However, survival rates may reach 80% after liver transplantation . FVH is typically sporadic, as opposed to epidemic, suggesting that it is not caused by a new more virulent viral strain . Title: Inherited IL-18BP deficiency in human fulminant viral hepatitis", "Passage: Factor V, 100% . On day 8 of infection, the patient was hospitalized for incoherent speech, jaundice, appetite loss, gingival bleeding, and petechiae. During physical examination at the emergency unit, the patient was unconscious, with icterus, hepatomegaly, and a fever . The patient was diagnosed with FVH due to HAV infection. On day 9, liver function tests revealed high levels of cytolysis, with a PT of 14%, factor V levels at 30%, and a Glasgow coma scale score of 8 . The patient underwent liver transplantation but died a day later of multiple organ failure . Histological examinations of the", "Title: Estimating the number of infections and the impact of non-\nPassage: The true number of infected individuals, C, is modelled using a discrete renewal process. This approach Title: Estimating the number of infections and the impact of non-\nPassage: people infected. Title: Estimating the number of infections and the impact of non-\nPassage: gain intuition that this is data driven and not simply a consequence of highly constrained model Title: Estimating the number of infections and the impact of non-\nPassage: appropriate and plausible.", "Title: Virus contaminations of cell cultures \u2013 A biotechnological view\nPassage: Only few harvests need to be tested . c Old cells may be from production runs or from a separate culture kept in continuous culture for a long period and prepared for this analysis of 'limit of cell age' only . Extensive testing performed as part of the qualification of the MCB regarding absence of latent virus, inducible by cultivation on production conditions. d A very large sample volume for testing would be required for statistics of a sufficiently sensitive detection of low virus titers. Title: Production of high titre disabled infectious single cycle (DISC) HSV from a microcarrier culture", "Passage: CPE 60-72 h after infection, the cultures were harvested. Infectious DISC-HSV released from the CR2 cells was quantified using a TCID 50 assay and was again compared to the titre achieved from the equivalent roller bottle culture harvests. The results are shown in Table 1 . Typically 4-7.0 \u00d7 10 11 total pfu from a 15 l culture was achieved, with a period of approximately 9 h during which this high titre was sustained. From an equivalent number of 388 roller bottles we would expect to achieve approximately 3.88 \u00d7 10 11 total pfu. Our results, therefore, compare very favourably Title: Tips and Tricks for Validation of Quality Control Analytical Methods in Good Manufacturing Practice Mesenchymal Stromal Cell Production", "Passage: measuring the quantity as absorbance , the cell suspensions were diluted to obtain two concentrations, one of 10-100 CFU/mL and one of 100-1000 CFU/mL. Each batch of culture medium was tested for sterility and fertility before use according to Ph considering the quantity results shown on the report of the external quality program. Title: Tips and Tricks for Validation of Quality Control Analytical Methods in Good Manufacturing Practice Mesenchymal Stromal Cell Production", "Passage: removed by washing with phosphate-buffered saline with complete medium change. The cultures were daily monitored for colony appearance, and the culture medium was changed every three days. At 80% confluence, the cells were detached using 25 mL/layer of TrypLE-Select , at the version in use at the moment of validation. The lyophilized bacterial strains, yeast, and fungus were appropriately prepared and isolated in Casein Soybean Digest Agar and Sabouraud, right-agar plates . After incubation at the optimum growth conditions, the strains were stored at 4\u00b0C \u00b1 2. For use, they were recultivated in agar plates in specific conditions and after", "Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China\nPassage: We shall analyze the daily data for the number of confirmed cases in mainland China, which origins from the National Health Commission of the People's Republic of China . A part of the official diagram is shown in Fig. 1 . For calculations, we have used the data for the period of time from January 16 to February 9, 2020. The numbers shown after February 9 were used for verification of predictions. Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China\nPassage: 9 1975 10 25 42638 Unknown 26 10 2744 11 26 44653 Unknown 27 11 4515 12 27 46472 58761 28 12 5974 13 28 48467 63851 29 13 7711 14 29 49970 66492 30 14 9692 ----31 15 11791 ---- Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China", "Passage: On February 12, 2020, the National Health Commission of the People's Republic of China has added 12289 new cases as \"clinically diagnosed cases\". The cases, reported by this official organization before, have the name of \"tested confirmed cases\" . To avoid confusiong, we will denote \"tested confirmed cases\" as Wj; j corresponds to the different time moments tj . Let us denote the \"clinically diagnosed cases\" as Qj. The sum of Wj and Qj is shown in the last column in Fig. 1 and in the Table. The Table shows that the precise time of the epidemic beginning t0 is Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "Passage: As of 24 January 2020, the cumulative incidence in China is 830 cases, of which 549 cases were diagnosed in Hubei, 26 in Beijing, 20 in Shanghai, and 53 in Guangdong. Additionally, twenty-six deaths have been linked to the outbreak , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020. Considering that enhanced surveillance has been underway in these importing countries, case ascertainment has been perhaps better in exported case data.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: subsequently spreads to another . Among those with progressive illness, the median time to death is 11 to 13 days, ranging from five to 27 days . Fever and gastrointestinal symptoms may form a prodrome, after which symptoms decline, only to be followed by a more severe systemic and respiratory syndrome . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: families and healthcare settings . Clinical pictures of this infection varied from asymptomatic to mild respiratory symptoms to severe respiratory distress and death . Severe ailment can often cause respiratory catastrophes that need mechanical ventilation and support in ICUs across different healthcare settings . Studies have suggested an incubation period of 16 days with a mean of 5-6 days , while the median time until death is 11-13 days among severely ill patients . e gold standard test for the detection of this virus is real-time reverse-transcription polymerase chain reaction assays . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Although DCs appear to suffer the equivalent of a 'common cold' from MERS-CoV infection, in humans, the virus can be a more serious and opportunistic pathogen associated with the death of up to 40 % of reported cases. It has yet to be established whether infections thought to have been acquired from an animal source produce a more severe outcome than those spread between humans . Studies have established that the mean incubation period for MERS is five to six days, ranging from two to 16 days, with 13 to 14 days between when illness begins in one person and Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: 7 days, and the test is subsequently repeated after every 3 days until a negative result is obtained .", "Title: Preparation of MS2 Phage-Like Particles and Their Use As Potential Process Control Viruses for Detection and Quantification of Enteric RNA Viruses in Different Matrices\nPassage: Reverse transcription was carried out using PrimeScript Reverse Transcriptase with slight modifications to the manufacturer's protocol. The RT mixture contained 0.5 nmol of dNTP mix , 20,000 molecules of IAC RNA, 2 pmol of both reverse primers , 4 \u00b5l of PrimeScript reaction buffer, 5 U of reverse transcriptase, 1 U of RNase inhibitor and 5 \u00b5l of isolated RNA. The reaction was performed at 50 \u2022 C for 1 h followed by 75 \u2022 C for 15 min and a cooling step at 10 \u2022 C. Title: A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity", "Passage: In brief, the tailed RNA product was mixed with 0.5 mM dNTP and 2.5 mM synthesized primer and incubated at 65 \u2218 C for 5 min, followed by incubation on ice for 5 min. The reaction mix was then added with 20 mM Tris , 50 mM KCl, 5 mM MgCl 2 , 10 mM DTT, 40 U RNaseOUT, and 200 U SuperScript III . RT reaction was performed according to the manufacturer's instructions. Reverse transcription products were separated on a 10% polyacrylamide TBE-urea gel as described earlier. The extended first-strand product band was expected to be approximately 100 nt, Title: RNA-Dependent RNA Polymerase Speed and Fidelity are not the Only Determinants of the Mechanism or Efficiency of Recombination", "Passage: Viral RNA was purified from virus stocks by using QiaAmp viral RNA purification kit and used for RT-qPCR to determine genome copies. This analysis was performed by the Genomics Core Facility of the Pennsylvania State University. DNAse-treated RNA was reverse-transcribed using the High Capacity cDNA Reverse Transcription kit following the protocol provided with the kit. Quantification by real-time qPCR was done with 2X TaqMan Universal PCR Master Mix in a volume of 20 \u00b5L, with primers 5 -ACCCCTGGTAGCAATCAATATCTTAC-3 and 5 -TTCTTTACTTCACCGGGTATGTCA-3 , and probe 5 - TGTGCGCTGCCTGAATTTGATGTGA-3 in a 7300 Real-Time qPCR System machine. A standard curve was generated using Title: Variation in RNA Virus Mutation Rates across Host Cells", "Passage: A 96-well plate containing 10 4 cells per well was inoculated with a limiting dilution of the viral stock such that approximately 10% of wells were infected. Plates were incubated at 37uC for 24 h, inspected under the microscope for cytopathic effects, and freezethawed to allow release of intracellular viruses. Viral RNA was purified from the supernatant of each of five positive wells and reverse-transcribed using AccuScript High Fidelity Reverse Transcripatse, and the cDNA was PCR-amplified using Phusion High Fidelity DNA polymerase and specific primers located in the P, G and L genes, as indicated. PCR products were cloned and", "Title: Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins\nPassage: that are not bound to the mutant NS1B protein, although only a small percentage of the total NP proteins in mutant virus-infected cells, act in a dominant-negative manner to terminate the oligomerization of unconjugated NP molecules, resulting in incomplete NP oligomers containing ISGylated NP. This is the first demonstration that ISGylated viral proteins can act as dominant-negative inhibitors of the oligomerization of their much more abundant unconjugated counterparts in virusinfected cells. Title: Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus", "Passage: The mechanism of dominant-negative inhibition by the C-terminal deletion mutant of hnRNP A1 To understand the underlying mechanism of the inhibition of MHV RNA transcription by the C-terminal-deletion mutant of hnRNP A1, we \u00aerst examined the RNA-and protein-binding properties of this mutant protein. Title: Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition", "Passage: In vitro DENV inhibition. Encouraged by the previous results, we investigated the in vitro inhibition of DENV through standard antiviral, plaque-forming half-maximum effective concentration assays. Briefly, the DENV viral particles were incubated with different concentrations of each inhibitor in human serum and the remaining infectivity was determined by a plaque reduction assay . The dose-dependent inhibition of DENV for the monovalent aptamer and each of the scaffold-aptamer complexes was examined . The EC 50 value of the DNA star-aptamer complex for DENV infection inhibition was 2 nM, whereas the EC 50 value for the monovalent aptamer was 15 \u00b5M . Title: Enterovirus Control of Translation and RNA Granule Stress Responses", "Passage: A final hypothesis is that production of G3BP1 cleavage fragments may be more important than the loss of intact G3BP1 through the production of dominant negative inhibitors. The expression of certain G3BP truncations in cells revealed some degree of dominant negative activity . The G3BP1 fragments generated by CVB3 3C pro and the C-terminal RNA binding domain are inhibitors of SGs . Further, deletion of the NTF2-like domain is sufficient produce a dominant negative factor . Taken together, this may indicate that several interaction domains along the length of G3BP are needed for SG formation. Consistent with this interpretation, G3BP1", "Title: Effects and cost of glycyrrhizin in the treatment of upper respiratory tract infections in members of the Japanese maritime self-defense force: Preliminary report of a prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment clinical trial", "Passage: The pharmacologic action of glycyrrhizin, the active component of licorice root, has been shown to produce anti-inflammatory activity, 4'5 modulation of the immune system, 6'7 inhibition of virus growth, and inactivation of viruses. 8-~\u00b0 Glycyrrhizin also has been found to inhibit virus growth in mice infected with influenza viruses and to improve outcomes. ~ ~ Glycyrrhizin is most typically used to treat chronic hepatitis and allergic dermatitis as urticaria in Japan and has occasionally been used to treat URTIs without prospective, randomized, double-blind, controlled study methods. ~2 Title: Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species", "Passage: of 3.6-13.1% in dried roots . G consists of a disaccharide of two glucuronic acid molecules bound to the pentacyclic triterpene glycyrrhetinic acid , which exists in two isomers : the trans and the cis form . G exhibits potent hydrocortisone-like anti-inflammatory, antiulcer, antiviral, and antihepatotoxic activities whereas GA is a potent antibiotic against ulcer causing Helicobacter pylori . Title: Effects and cost of glycyrrhizin in the treatment of upper respiratory tract infections in members of the Japanese maritime self-defense force: Preliminary report of a prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment clinical trial", "Passage: glycyrrhizin also has been used to treat human immunodeficiency virus-1. Infrequent AEs, such as increased blood pressure and hypokalemia, have been reported in some patients after several months of glycyrrhizin HCV treatment. However, in this study in which glycyrrhizin was used for a short time, no AEs were reported. Title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression\nPassage: Glycyrrhizin was obtained from Minophagen Pharmaceuticals Co., Ltd. .", "Title: Estimating the number of infections and the impact of non-\nPassage: Italy 9.8% Title: Estimating the number of infections and the impact of non-\nPassage: countries between 7 and 43 million individuals have been infected with SARS-CoV-Z up to 28th March, Title: Estimating the number of infections and the impact of non-\nPassage: https://www.gazzettaufficiale.it/eli/id/2020/03/08/20A01522/sg . Title: Estimating the number of infections and the impact of non-\nPassage: http://www.salute.gov.it/portale/nuovocoronavirus/dettaglioVideoNuovoCoronavirus.jsp?lingua=ita", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: For viral vectors, the impact of cell-mediated immunity was more pronounced, and as depicted in Table 2 , almost always resulted in a reduction in the subsequent immune response. Presumably this is because viruses will induce neutralizing antibody on the first dose, and in subsequent doses this antibody will limit the number of transduced cells, therefore limiting the responses. This is particularly a problem with a common viral vector such as Ad, where a large proportion of the population will have immunological memory against common serotypes . As these authors conclude, it will be possible to utilize such vectors only Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: All these studies on the effect of pre-existing immunity discuss the impact on humoral responses. Sevil Domenech and colleagues reported that pre-exposing animals to the homologous Salmonella vector leads to a significant reduction in CD8 + responses; however, exposure of animals to a heterologous strain leads to significantly higher CD8 + responses . Title: Recombinant vector vaccine evolution", "Passage: Although recombinant vector vaccines are not yet in widespread use, many are under development , and their success may rest on understanding within-host evolution. Here we explore how the combination of evolution during the process of vaccine manufacture and during its within-host dynamics following vaccination could affect the immune responses elicited by a recombinant vector vaccine and reduce its efficacy-the specific interaction between evolution and immunity. We consider viral vaccines and focus on vaccines that cause shortduration infections. The ideas we discuss also apply to live vaccines of bacteria and other pathogens.", "Title: Identification of ireA, 0007, 0008, and 2235 as TonB-dependent receptors in the avian pathogenic Escherichia coli strain DE205B\nPassage: Iron is a vital micronutrient that regulates enzyme activity and metabolism. This element plays a key role in basic cellular processes, such as cellular respiration, DNA replication, and electron transport and is accordingly essential for bacterial survival in host tissues . Furthermore, iron is a necessary growth factor for bacteria and is reportedly involved in the expression of bacterial virulence factors . Iron uptake factors evidently play a pivotal role in E. coli growth and pathogenesis. Bacteria employ different strategies to absorb iron from their environment, including siderophore-mediated iron uptake, which occurs on the cell surface . In addition, bacteria Title: Insight into the Interaction of Metal Ions with TroA from Streptococcus suis", "Passage: Almost one third of proteins in nature depend on a particular metal for their diverse functions and divalent metal cations are essential for bacteria . For instance, manganese plays a primary antioxidant role in bacteria and affects bacterial pathogenesis . Zinc is one of the most abundant metals in bacteria and is an essential co-factor of many metabolic enzymes and transcription factors . The Mn 2+ ion is characterized as hard metal and tends to prefer hard ligands, while zinc prefers soft ligands . To obtain appropriate cellular concentrations of transition metal ions, bacteria have evolved elaborate machineries to transport Title: Identification of ireA, 0007, 0008, and 2235 as TonB-dependent receptors in the avian pathogenic Escherichia coli strain DE205B", "Passage: either excessively reduce the external pH or dissolve iron oxide to meet their iron requirements by reducing ferric iron to a relatively soluble ferrous form. Another common strategy is to synthesize and secrete iron chelators, such as siderophores, as intracellular iron is rarely found in natural conditions, and Fe 2+ can be readily oxidized to Fe 3+ in the presence of oxygen and water . Siderophores then combine with the available iron to form an iron-siderophore complex, which binds to specific receptor proteins on the bacterial cell surface, consequently entering cells via the TonBdependent transport system, followed by iron release. Title: Identification of ireA, 0007, 0008, and 2235 as TonB-dependent receptors in the avian pathogenic Escherichia coli strain DE205B", "Passage: TBDRs are known to actively transport ferric-siderophore complexes in Gram-negative bacteria, and they also transport diverse antibiotics, vitamins, nickel complexes, and carbohydrates . Transporters involved in iron uptake have very strict siderophore selectivity. A strong correlation exists between the amount of iron and siderophores that bacteria can use and the number of genes encoding iron-regulated TBDRs . In simple terms, iron depletion triggers the upregulation of genes encoding TBDRs.", "Title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing\nPassage: To establish the phylogeographic map, HTNV tripartite genome sequences from A. agrarius captured in the endemic and military training areas near the demilitarized zone were completely acquired using RT-PCR. Compared with the genomic HTNV sequences of patients and the rodent hosts, the site where HFRS patients acquired HTNV infection was suggested by the phylogeographic analyses . ROKA13-8 and ROKA14-11 formed a cluster with HTNV strains from Cheorwon-B and TBTA-S, respectively. Patient ROKA13-8 was assigned to Hwacheon, but conducted military training in Cheorwon. ROKA13-8 was phylogenetically associated with HTNV strains in Cheorwon-B suggesting the Soldier was most likely infected with HTNV Title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing", "Passage: during the training in Cheorwon. This result also suggested that patient ROKA14-11 conducted military activity and was the most likely infected with HTNV near TBTA-S in Paju. Phylogenetic analysis of US Army HFRS patient US8A14-2 showed a close relationship with HTNV strains from DN in Paju. This result and clinical records suggested the Soldier was the most likely infected with HTNV at DN between November 17 and 20, fell within the normal incubation period of HTNV. The US Army HFRS patient US8A15-1 conducted military training at MPRC, Pocheon. The phylogenetic association of US8A15-1 with HTNV strains in Pocheon identified the Title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing", "Passage: For phylogeographic analyses, the whole genome sequence of 26 HTNV strains was acquired from rodents collected in endemic areas in the ROK . The HTNV strains in the phylogenetic tree consisted of 3 strains from Twin Bridge Training Area South , 3 strains from Twin Bridge Training Area North , 3 strains from Dagmar North in Paju, 2 strains from Fire Point 131 in Yeoncheon, 4 strains from Nightmare Range and Rodriguez Multi-Purpose Range Complex in Pocheon in Gyeonggi province, and 6 strains from Cheorwon-A and B , 2 strains from Hwacheon, and 3 strains from Yanggu in Gangwon province. Title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing\nPassage: coverage of HTNV L segment from US8A14-2 was 96.1% whereas the HTNV M and S segments were completely sequenced. The genomic sequence of HTNV from US8A15-1 was acquired by 87.4%, 98.2%, and 100% for L, M, and S segments, respectively.", "Title: Primary biliary cirrhosis\nPassage: . Stage 1 disease is characterized by portal inflammation with granulomatous destruction of the bile ducts, although granulomas are often not seen. Stage 2 is characterized by periportal hepatitis and bile duct proliferation. Presence of fibrous septa or bridging necrosis is defined as stage 3 and cirrhosis as stage 4 . Findings of fibrotic or cirrhotic changes are accompanied by a worse prognosis . Florid duct lesions as defined by focal duct obliteration and granuloma formation are regarded as typical for PBC. The liver is not uniformly involved, and features of all four stages of PBC can be found in Title: Markers of exacerbation severity in chronic obstructive pulmonary disease\nPassage: episodes . Title: Th17 profile in COPD exacerbations", "Passage: episodes . Title: Th17 profile in COPD exacerbations\nPassage: The Global Initiative for Chronic Obstructive Lung Disease defines COPD as a common and treatable disease characterized by the persistent limitation of airflow, which is usually progressive and associated with an increase in the inflammatory response in the airways and in the lungs by harmful particles and gases. 10 Also, this guide defines exacerbations as an acute event characterized by worsening of patient's respiratory symptoms that go beyond daily variations and leads to a change in medication. 6, 10, 48 In addition, the guide also points out that a patient with frequent exacerbating COPD will be considered when he has Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Chronic obstructive pulmonary disease is a respiratory disease characterized by an airflow limitation and inflammation of the lower airways . As the disease worsens, some patients experience 'exacerbations' of their principal symptoms of dyspnoea, cough and sputum. These exacerbations frequently result in a visit to a general practitioner's office or to a local hospital for treatment. Exacerbations occur in COPD patients at a median of three times a year with half of them being unreported . The heterogeneity of COPD exacerbations make them difficult to define, classify and manage due to their range of symptoms, varied treatment requirements, seasonal occurrence,", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: Koch recognized as early as 1891 that associating the presence of a certain agent with a certain disease is complex, and he therefore postulated guidelines that should be followed before an agent can be classified as a pathogen . His postulates can be summarized in three points: The microbe occurs in every case of the disease in question and under circumstances which can account for the pathological changes and clinical course of the disease; the microbe occurs in no other disease as a fortuitous and nonpathogenic parasite; and , after being fully isolated from the body and repeatedly grown in Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond", "Passage: been made to adjust the Koch's postulates specifically for viruses and the current methodologies deployed , fulfilling these postulates is still not feasible on most occasions due to the lack of an efficient cell culture system, difficulties in antigen synthesis and high levels of viral genetic diversity within viral groups, reviewed in the literature . Title: Cancer Biomarker Discovery: The Entropic Hallmark", "Passage: however, that the 29 samples seem to be separating in three different clusters. Whether we can argue about the existence or not of these gaps in Normalized Shannon Entropy, it is clear that there seems to be a progression as we have seen with Lapointe et al's dataset. There is a group of three samples with Gleason pattern 3 that seem to have the the largest Normalized Shannon Entropy values. There is also a cluster that only contains samples of either Gleason pattern 4 and 5, all with Normalized Shannon Entropy values smaller than 0.985. Title: Cancer Biomarker Discovery: The Entropic Hallmark", "Passage: This raised a suspicion about the true nature of this phenomenon. If the labelling is correct, this may indicate a subsampled group of prostate cancer that has Gleason 3 pattern characteristics but very low entropy. Alternatively, it may indicate an experimental bias for reasons we can not explain with the available clinical information. In order to clarify the situation, and see if we can declare these two samples as outliers of the other group, we performed another experiment. We have now computed two modified complexities, which we will call M- Gleason 3 and M-Gleason 5 . The names are probably", "Title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study\nPassage: Overall, few cases of H7 virus transmission to mammals have ever been reported in Asia and N9 virus infections in human have never been documented anywhere in the world except H7N9 . The H7N9 variants currently in circulation most likely evolved through a combination of genes from viruses in Beijing bramblings, Zhejiang ducks, and Korean wild birds according to report by Chinese scientists. Human infections with highly pathogenic H7 viruses generally resulted in conjunctivitis or uncomplicated influenza Title: Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People\u2019s Republic of China", "Passage: From our study we found that most H7N9 cases had LPMs exposure history, and in Zhejiang Province and Guangdong Province, routine environmental surveillance showed that LPMs were the most contaminated place by H7N9 virus, and the detection of H7N9 virus spiked in cold months , which was in accordance with the epidemic trends of the H7N9 in mainland China. And several other subtypes of human infections of avian influenza have also been detected in China, including H5N1, H5N6, H10N8, and H9N2 et al. Most of the infections also resulted from the live poultry exposure or poultry related environment exposure, especially Title: Epidemiological, clinical, and virologic features of two family clusters of avian influenza A (H7N9) virus infections in Southeast China", "Passage: In early 2013, an outbreak of H7N9 virus infections occurred in Eastern China, which generated global concern 1 . To date, the virus has caused four outbreaks in humans, and most cases occurred during winter and spring 25 . The H7N9 virus is a low pathogenic avian influenza A virus, and it does not cause identifiable illness or death in poultry, whereas humans act as sentinels for the presence of these viruses in avian infections 17 . Currently, humans get infected with the H7N9 virus predominantly through contact with asymptomatic poultry, and sporadically via direct contact or exposure to environments Title: A family cluster of three confirmed cases infected with avian influenza A (H7N9) virus in Zhejiang Province of China", "Passage: Following written informed consent, a structured questionnaire was used to gather demographic information and data on use of personal protective equipment, antiviral chemoprophylaxis, symptoms, and potential risk factors for H7N9 infection during the two weeks starting from their last exposure to H7N9-infected cases.", "Title: Automatic Detection and Quantification of Tree-in-Bud (TIB) Opacities from CT Scans\nPassage: The SI is a statistical measurement and used to define intrinsic shape of the localized structure within the image , . SI values are encoded as a continuous range of values between \u22121 and 1, with zero SI indicates saddle-like local structures, +1 and \u22121 SI values indicate umbilical minima and maxima , and midpoints of the two half-intervals indicate concave and convex parabolic or line-like structures . SI can simply be computed through principal curvatures as follows: Title: The social benefits of private infectious disease-risk mitigation", "Passage: As is standard with such a model, we let c be the nominal contact volume of all individuals. P SI is the conditional probability that a contact made by a susceptible individual, S, is with an infectious individual, I, and \u03b3 is the rate at which an individual recovers and becomes immune, R. Title: Validation of the Munich ChronoType Questionnaire in Korean Older Adults(*)\nPassage: The ISI is a 7-item index developed by Bastien et al. 38 and assesses the severity of insomnia, satisfaction with current sleep, and worries about sleep problems during the last two weeks. The ISI total score ranges from 0 to 28, with higher scores reflecting higher severity of insomnia symptoms. A Korean version of the ISI has been validated in Korean samples. 39 The internal consistency was 0.83 in this sample. Title: Social clustering in epidemic spread on coevolving networks", "Passage: Moreover, inspired by Ref. , in Fig. 21 we include the evolution of the fraction of SI links S I , the effective branching factor \u03ba S IS \u2261 S SI /S I , and the average number of connections that susceptible nodes share with other susceptibles C SS \u2261 S S / as well as the AME approximation for these quantities. In an SIS model, S I measures the level of links that could potentially pass the disease, \u03ba S IS measures the average number of susceptible neighbors that the infected end of a SI link has, and C", "Title: The CCR5\u039432 allele is not a major predisposing factor for severe H1N1pdm09 infection\nPassage: Indeed, studies based on historical registries indicated that genetic factors affect the risk of death due to influenza virus infection . Likewise, the familial aggregation of influenza A/H5N1 cases, the paucity of cases among highly exposed groups, and the occurrence of related cases separated in time and space led Horby and coworkers to indicate that host genetic factors play an important role in the susceptibility to this infection . Title: The CCR5\u039432 allele is not a major predisposing factor for severe H1N1pdm09 infection", "Passage: Clearly, the identification of host genetic factors that modulate the susceptibility to and the severity of influenza virus infection is of paramount importance to develop preventive strategies and therapeutic interventions. Title: Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance neuraminidase mutation shows a small compromise in enzyme activity and viral fitness\nPassage: virus to accommodate or even select for the H275Y mutation. Title: Multiple gene mutations identified in patients infected with influenza A (H7N9) virus", "Passage: susceptibility to viral infection, and that in the future, these mutations could provide information regarding risk of infection, especially poultry workers or family members of infected patients. Using a variety of computational genetic techniques, we identified 21 genes that showed a high rate of mutation in patients infected with H7N9 when compared to the general population. Among these genes, some have been identified in prior studies of H7N9 susceptibility genes 14 . For example, Wang et al. reported that IFITM3 dysfunction is associated with increased cytokine production during H7N9 infection and is correlated with mortality 14 . IFITM3 was reported", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: stem loop. Bat SARS-related CoV ZC45 did not have the SARS-COV SL6-like stem loop. Instead, it possessed two other stem loops in this region. All three strains had similar SL7 and SL8. The bat SARS-like CoV ZC45 also had an additional stem loop between SL7 and SL8. Overall, the 5 \u2032 -UTR of 2019-nCoV was more similar to that of SARS-CoV than the bat SARS-related CoV ZC 45. The biological relevance and effects of virulence of the 5 \u2032 -UTR structures should be investigated further. The 2019-nCoV had various 3 \u2032 -UTR structures, including BSL, S1, S2, S3, S4, L1, Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins", "Passage: Genomes were assembled using Sequencher 4.1.4 . Putative ORFs >100 amino acids were identified and annotated using SeqBuilder version 11.2.1 . Partial genes or genes that seemed interrupted were analyzed for potential introns using GENSCAN . The potential origin of replication for each genome was identified by locating a canonical nonanucleotide motif and confirming predicted stem-loop structures using Mfold with constraints applied to prevent hairpin formation within the nonanucleotide motif and a folding temperature set at 17 \u2022 C . Final annotated genomes have been deposited to GenBank with accession numbers KR528543-KR528569.", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Hantavirus diseases of man have long been suspected of having an immunopathogenic basis in part because of their relatively long incubation period of 2-3 weeks and the observed temporal association between immunologic derangements and the first appearance of signs and symptoms of hantavirus illness. HFRS and HCPS share many clinical features, leading many investigators to consider them to be, in essence, different manifestations of a similar pathogenic process, differing mainly in the primary target organs of disease expression . The pathogenesis of hantavirus infections is the topic of a continuously-updated review in the series UpToDate . Title: Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model", "Passage: Because prevention of challenge virus infection occurred only for intervals of \u22647 days and primary virus was detected for 5-7 days , a temporary state of immunity that affects challenge outcome may require the presence of primary virus. Animals shedding secondary virus after challenge were grouped according to whether the primary infection virus could be detected in URT samples after challenge, as a proxy for the presence of virus on the day of challenge. The kinetics of challenge virus shedding were compared between the groups . Title: Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model", "Passage: To investigate viral interference following infection with influenza virus, we systematically assessed the influence of a primary virus infection on the kinetics of a secondary virus challenge in the ferret model . Two intervals represented the start and peak of virus shedding, respectively, in the upper respiratory tract ; one interval corresponded to decreased virus shedding; and one interval reflected the end of virus shedding. Seroconversion typically occurs 7-12 days following infection ; thus, the 7-day interval and 2 later intervals represented the adaptive immune response . Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: adults in multicenter phase III clinical trials, three dose schedules at 0, 1, and 13 months were used. The seroconversion rate was 90.14% by IFA but only 23.24% by PRNT50 after two primary doses. One month after vaccination, the positive rate of serum was 87.32 and 45.07% according to IFA and PRNT50, respectively. The neutralizing antibody response of the two initial doses of Hantavax TM was very poor. Therefore, it is necessary to carry out enhanced immunization within 2-6 months to provide timely protection for high-risk groups .", "Title: Characterization of MDCK cells and evaluation of their ability to respond to infectious and non-infectious stressors\nPassage: To mimic infectious stressors, we chose Lipopolysaccharide , present in the external wall of Gram-negative bacteria and largely responsible for their toxicity. LPS is recognized by TLR4-coreceptors MD2 and CD14, which recognize the lipid A core of LPS. TLR4 transduces the signal via MyD88 and TRIF adapters to activate NF-jB-and/or IRF3mediated transcription of genes encoding pivotal molecules of the immune system, including cytokines and chemokines, which mimics major inflammatory response models . Moreover, LPS is of concern since it is a common contaminant of cell cultures. It is an amphipathic molecule which adheres to hydrophobic materials like plastics and glassware. Title: Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases", "Passage: Lipopolysaccharide is composed of three distinct domains, lipid A, a short core of oligosaccharide and the O-antigen polysaccharide . The lipid A domain is the bioactive component and is recognized during human infection. The composition of the O-antigen varies between different Gram-negative bacterial strains. The presence or absence of O chains determines whether LPS is considered rough or smooth . Full length O chains would render the LPS smooth while the absence or reduction of O-chains would make the LPS rough . Title: Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide", "Passage: Acute and chronic infection, especially that induced by Gramnegative bacteria is associated with increased risk of thrombosis and atherosclerotic disease . Little is known about the underlying cellular mechanisms responsible for these risks. Lipopolysaccharide , a component of the cell wall of Gram-negative bacteria, is an antigen which initiates inflammation and innate immune responses by interacting with Toll-like receptor 4 . TLR4 is expressed on the surface of cells, including leukocytes and platelets . Under physiological conditions, platelets and leukocytes circulate in quiescent state and do not interact with each other. However, once activated under pathophysiological conditions such as those Title: Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases", "Passage: Lipopolysaccharide is a potential drug target since its presence is critical in membrane stability and also it plays a prominent role in raising an immune response . LPS triggers the release of many inflammatory cytokines, in particular TNF\u03b1, interleukin-1\u03b2 and IL-6, and it has been implicated as the etiological agent of a variety of pathologies ranging from mild to lethal . Thus the structure, function and biosynthesis of LPS have been areas of intense research in the last decade .", "Title: Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses\nPassage: are responsible for the cytopathic response mediated by this receptor variant. Title: The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection", "Passage: CIITA . In addition, DNA-dependent activator of interferon regulatory factors has been identified as a DNA sensor . Various microbial components are recognized as their vague and common molecular shapes by PRRs. Early responses against virus infection are initiated on recognition of pathogen-associated molecular patterns by pattern recognition molecules, triggering two responses. One is the production of interferons resulting in an antiviral state as part of the innate immune response, and the second is maturation of dendritic cells to establish acquired immunity. In order to establish an infection within a host, viruses must escape from and/or suppress the immune system Title: Host Modulators of H1N1 Cytopathogenicity", "Passage: the participation of endosomes as a viral entry mechanism , it is tempting to speculate that RRAGD is a limiting host factor for viral corruption of mTOR regulation. Additional factors in this group are involved with the host defense response, p53-mediated cell death and vesicle maturation and trafficking. To test for false positives arising from off-target effects of siRNA treatment, we retested 88 siRNA pools as four individual oligos. Approximately 60% of siRNAs retested with two or more oligos reproducing the original phenotype . Title: Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses", "Passage: The fact that these two viruses are only cytopathic in M. dunni cells suggests involvement of the receptor-virus interaction for two reasons. First, the amino acid residue that is modified in both viruses has been identified as one of the critical amino acids forming the receptor binding site . Second, M. dunni cells differ from other mouse cells in their resistance to MoMLV , and these cells are known to carry a modified CAT-1 receptor . The dCAT-1 gene of M. dunni cells differs from the prototypical CAT-1 gene of the laboratory mouse in that the third extracellular loop that", "Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury\nPassage: Moreover, to link the intracellular iron content to the function of alveolar macrophages, we assessed the phagocytosis of alveolar macrophages, and found that the alveolar macrophages from Ad-shHepc1-treated mice showed less phagocytic ability than those from the control animals . Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury\nPassage: Hepcidin regulates iron metabolism by binding to ferroportin and causing its internalization and degradation. We therefore investigated the ferroportin levels in both whole lung tissue and alveolar macrophages. As expected, the ferroportin in the control mice was almost totally degraded, whereas a higher ferroportin level was observed in the hepcidin knockdown mice . Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: We further asked whether hepcidin gene modification in AECs had an impact on local and systemic iron metabolism. Of note, the knockdown of hepcidin in AECs resulted in less iron retention in the alveolar macrophages , whereas the iron contents in the spleen macrophages and serum iron concentration between the two groups showed no significant differences . Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: from Ad-shHepc1-treated mice showed less phagocytosis ability than those from the control animals. Since liver is the major source of systemic hepcidin, in the current study liver hepcidin levels were not affected and circulating iron concentrations were comparable between the Ad-shNeg-and Ad-shHepc1-treated mice. Therefore, the function of circulating leukocytes should not be influenced. Although the inciting injury is remote, when the bacteria circulating in the blood stream invaded the lung after CLP, the decreased phagocytosis function of the alveolar macrophages from the Ad-shHepc1-treated mice could result in bacterial accumulation in the lung. In addition, as hepcidin exhibits broad spectrum antimicrobial", "Title: Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes\nPassage: An SSI can increase hospital stay by about six days and can add 10-20 % to hospital costs, even leading to death; therefore, prevention and control should be an . SSIs may occur following any surgical incision, even after the use of minimally invasive techniques, so SSIs need to be reported through systematic monitoring programmes for nosocomial infection . We showed that patients suffering from SSI in our cohort had longer ICU stays. However, we do not think this was simply a surrogate of higher illness severity in the SSI group because of the comparable severity scores between groups. Title: Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes", "Passage: The increasing trend to reduce hospital stays by implementing innovative surgical techniques makes it necessary to ensure that accurate measurement and monitoring of adverse events can take place after discharge. Without doing so, we cannot establish the real impact of SSI on morbidity and mortality . Control measures with an emphasis on the education of healthcare professionals, such as frequent hand washing and the need to isolate patients with multi-resistant bacteria in cluster units, are necessary to reduce SSI rates . Although the total elimination of SSI is not possible, a reduction in the rate of infection to a minimum Title: Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes", "Passage: or drainage . Consequently, the treatment of SSI leads to increased costs, especially when we consider the high number of surgical procedures and their complexity in a typical referral hospital . Title: Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance\nPassage: respiratory infections and SARI-related mortality and another for influenza-like illness based in ambulatory clinics. Sentinel surveillance for influenza can provide information on trends in viral circulation patterns and seasonality, along with virus characteristics to help guide decisions on vaccine composition. However, healthcare seeking behaviors can affect who accesses care at the sentinel site, limiting the ability to gather information to guide public health policies. Without understanding patterns of healthcare seeking behavior, it is not possible to calculate the burden of disease, generalize findings to a larger population or identify risk groups.", "Title: Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection\nPassage: as 3 days postfertilization, coinciding with the attachment of the blastocyst to the uterine wall, and were believed to be critical for protecting the semiallotypic fetus from the maternal immune system during pregnancy in, at least, primates . Title: Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein", "Passage: The first signs of disruption of Golgi morphology largely began during or even preceding the accumulation of visible 3A signal , suggesting that local changes to morphology occur rapidly and may be triggered by 3A accumulation in regions of the Golgi apparatus outside the imaging plane. To facilitate the detection of the whole Golgi complex and to monitor large-scale changes in Golgi morphology, imaging was carried out using a wider confocal pinhole . Global Golgi fragmentation typically began 10 to 30 min after 3A started to accumulate in large amounts , which presumably reflects the time taken for the cumulative Title: Apoptotic signals induce specific degradation of ribosomal RNA in yeast", "Passage: W235 situated downstream of the expected cleavage sites . Similarly, major cleavage sites were analysed in 16-day old chronologically aged cells using the same primers and mapped at positions +601-602 and +478-501. According to the secondary structure of the 25S rRNA taken from , the regions where mapped cleavages occur are located at unpaired nucleotides in loops or bulges. This points to the action of single-stranded RNA nucleases. Title: Dynamics of the Developing Chick Chorioallantoic Membrane Assessed by Stereology, Allometry, Immunohistochemistry and Molecular Analysis\nPassage: It has previously been reported that the rapid phase of angiogenesis is E10 and after initiation of endothelial cytodifferentiation at E14 . Elsewhere, Baum and co-workers found expression of VEGF-A to have peaks at E8-E9 and also at E11-E12 while recently, a peak at E7 and E18 was reported .", "Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?\nPassage: hosts. However, these data indicate their possible involvement in the transmission function of EBOV, bridging the maintenance host with human populations during a spillover event . The EBOV susceptibility and exposure of many other potential forest hosts, including invertebrates, birds, bats, monkeys, rodents, and other small mammals, have been tested in the field or experimentally with an interestingly large amount of negative results ). A few monkey and bat individuals serologically positive to EBV antigen represent the only exceptions . Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?", "Passage: hosts. However, these data indicate their possible involvement in the transmission function of EBOV, bridging the maintenance host with human populations during a spillover event . The EBOV susceptibility and exposure of many other potential forest hosts, including invertebrates, birds, bats, monkeys, rodents, and other small mammals, have been tested in the field or experimentally with an interestingly large amount of negative results ). A few monkey and bat individuals serologically positive to EBV antigen represent the only exceptions . Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?", "Passage: Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles indicate a maintenance function play by the host; arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. Main maintenance hypothesis: there is one bat Figure 1 . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles indicate a maintenance function play by the host; arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?", "Passage: Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles indicate a maintenance function play by the host; arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. Main maintenance hypothesis: there is one bat Figure 1 . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles indicate a maintenance function play by the host; arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally", "Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: f. It might be noted that including the early infection SPARTAC cohort may be reducing their power, as these individuals may not have been infected long enough for escape to have occurred, thereby diluting the escape signal . Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: f. It might be noted that including the early infection SPARTAC cohort may be reducing their power, as these individuals may not have been infected long enough for escape to have occurred, thereby diluting the escape signal . Title: Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa", "Passage: can reveal structural changes in transmission due to control or behavioural changes, and it can capture fluctuating incidence data, e.g. in Conakry, Guinea. Also, the migration fractions are independent of the extent of the spatial dispersal. This allows for the situation where few people migrate, but when they do, they do so over large distances, as has, for instance, been estimated for Liberia. The method by Yang et al. does not make this distinction, but includes the home district in the migration matrix. This may explain why they find a lower proportion of local transmissions than we do . By Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: This is an interesting point, though we feel the increased sample size gained by inclusion of the SPARTAC cohort outweighs any issues with sampling design.", "Title: Inferring viral quasispecies spectra from 454 pyrosequencing reads\nPassage: of the reads that varies from 20K up to 100K and the average read length that varies from 200bp up to 600bp. Title: Inferring viral quasispecies spectra from 454 pyrosequencing reads\nPassage: The data set Data1 has been received from HCV Research Group in Institute of Biomedical Research, at University of Birmingham. Data1 contains 30,927 reads obtained from the 5.2kb-long fragment of HCV-1a genome . The average read length average is 292bp but it significantly varies as well as the depth of position coverage . The depth of reads coverage variability is due to a strong bias in the sequence start points, reflecting the secondary structure of the template DNA or RNA used to generate the initial PCR products. As a result, shorter reads are produced by GC-rich sequences. Data1 is available Title: Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands", "Passage: further study . Median length of predicted proteins on these reads was 75 amino acids showing error correction had not been sufficient to correct for the enriched presence of stop codons resulting from indel errors. Therefore, an alternative approach to gene calling was developed. VirION reads spanning genomic islands were trimmed at the 5' and 3' end to leave only the read fragment mapping within the genomic island, and these fragments were used as a query in a BLASTx search against the NR database using diamond , with the following settings: Title: Deep Sequencing to Identify the Causes of Viral Encephalitis\nPassage: Assembly of reads that aligned to the taxon-specific follow up databases resulted in apparently viral contigs ranging from 66 to 4019 bp long in 5 of the 7 encephalitis samples . These contigs were re-aligned to the taxon-specific database as well as the human genome with MegaBLAST.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: effective management of chronic inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Text: The prevalence of chronic airway inflammatory disease is increasing worldwide especially in developed nations . This disease is characterized by airway inflammation leading to complications such as coughing, wheezing and shortness of breath. The disease can manifest in both the upper airway and lower airway which greatly affect the patients' quality of life . Treatment and management vary greatly in efficacy due to the complexity and heterogeneity of the disease. This is further complicated by the effect of episodic exacerbations of the disease, defined as worsening of disease symptoms including wheeze, cough, breathlessness and chest tightness . Such exacerbations Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: specific mediators to facilitate viral targeting and clearance, including type II interferon , IL-2, IL-4, IL-5, IL-9, and IL-12 . These factors heighten local inflammation and the infiltration of granulocytes, T-cells and B-cells . The increased inflammation, in turn, worsens the symptoms of airway diseases.", "Title: Estimating the number of infections and the impact of non-\nPassage: countries between 7 and 43 million individuals have been infected with SARS-CoV-Z up to 28th March, Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: According to the situation report published by the WHO on 28 January 2020 , a total of 2798 confirmed 2019-nCoV cases have been reported globally; of these, 2761 cases were from China, including Hong Kong , Macau and Taipei . Thirty-seven confirmed cases have been reported outside of China in eleven countries in Europe, North America, Australia and Asia; of these 37 exported cases, 36 had a travel history from China or an epidemiological link to a case from China. Of the confirmed cases in China, 461 have been reported as severely ill, with 80 deaths to date. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: SARS-CoV and MERS-CoV cause severe disease, but despite the initial R0 estimations of greater than 2.0 for SARS-CoV , and some large outbreaks, neither were as transmissible as initial concerns suggested. SARS-CoV caused 8098 reported cases and 774 deaths in 37 countries before the epidemic was controlled. Control was thought to have been possible because a high proportion of cases were severe, making it easier to rapidly identify and isolate infected individuals. In addition, the virus was present at lower levels in upper airway secretions. There was no secondary transmission in the United States from the 8 imported cases, although Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Text: The emergence and outbreak of a newly discovered acute respiratory disease in Wuhan, China, has affected greater than 40,000 people, and killed more than 1,000 as of Feb. 10, 2020. A new human coronavirus, SARS-CoV-2, was quickly identified, and the associated disease is now referred to as coronavirus disease discovered in 2019 .", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,", "Passage: A novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 , was identified in December 2019 in the city of Wuhan, capital of Hubei Province, China, where cases were first confirmed . During December 2019\u2013February 2020, the number of confirmed cases increased drastically. Model estimates suggested that >75,000 persons were infected by January 25, 2020, and the epidemic had a doubling time of \u22486 days . By the end of January 2020, travel restrictions were implemented for Wuhan and neighboring cities. Nonetheless, the virus spread from Wuhan to other cities in China and outside the country. By February 4, Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: Text: On 29 December 2019 clinicians in a hospital in Wuhan City, China noticed a clustering of cases of unusual pneumonia with an apparent link to a market that sells live fish, poultry and animals to the public. This event was reported to the World Health Organisation on 31 December . Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine", "Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: To ensure success in the mission of shutting down the businesses that are still making money and that millions of people live on, the key issue is whether the decision maker and policy maker are aware of the extra dimension , which represents the single option that will result in apparent loss. In this sense, efforts to enhance environmental protection consciousness do, in fact, emphasize that there is an invisible \"green\" dimension. The purpose of thinking green is to make it clear that choosing to \"Chikui\" on an offered dimension that represents exploiting natural resource wealth will gain something on Title: Two Sides of Emotion: Exploring Positivity and Negativity in Six Basic Emotions across Cultures", "Passage: Specifically, Easterners tend to be dialectical when thinking about a situation in a manner that balances the positives and negatives. When things are going well, Easterners might expect a change for the worse, and when things are going badly, they might expect things to get better. This may prepare Easterners for unexpected situations. However, Westerners tend to focus more on one pattern-things will tend to stay as they are, good or bad. This thinking style may lead Westerners to think that things are rather consistent, leading them to concentrate on one side of an issue. Title: Suffering a Loss Is Good Fortune: Myth or Reality?", "Passage: The ability to make decisions and carry out effective actions for achieving rewards and avoiding punishments is central to intelligent life . In the real world, many decisions on important life events are to accept or reject an offered single option such as straightening of teeth, admission to college, counterfeit cash, a marriage proposal, a home mortgage, early retirement, or signing away an inheritance. Title: Two Sides of Emotion: Exploring Positivity and Negativity in Six Basic Emotions across Cultures", "Passage: is because if something is expected to change or fluctuate, it would not be taken in the extreme view. Linear thinkers, on the other hand, expect stability, so their thoughts might be grounded more in the extremes . One difference between dialectical and linear thinking styles lies in how people from different cultures view events. Easterners tend to take a more balanced view of negative events compared to Westerners . Indeed, findings suggest that people from dialectical and collectivist cultures make less polarized life quality judgments, whether negative or positive, compared to non-dialectical thinkers and individualist cultures .", "Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells\nPassage: Hepcidin is bound to plasma alpha-2 macroglobulin . Evidence suggests that other cells may express the hepcidin mRNA at a much lower level than the hepatocytes; the biological significance of the extra hepatic production of hepcidin remains uncertain. Plasma hepcidin is freely treated through glomeruli and in animals with normal kidney activity it quickly passes through the urine. In addition, a part of hepcidin is cleansed through degradation along with ferritin . Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: Hepcidin is a \u03b2-defensin-like antimicrobial peptide that is mainly produced by the liver. Hepcidin not only shows antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and yeasts, but also functions as a principal iron regulatory hormone . Hepcidin binds to the iron export protein ferroportin and induces its internalization and degradation, which leads to decreased cellular iron export and increased intracellular iron retention . Because iron is an essential nutrient for all organisms, hepcidin also restricts the iron available to invading microbes, thereby enhancing the host defense against pathogens . Furthermore, hepcidin can modulate the lipopolysaccharide -induced acute inflammatory response via Title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia", "Passage: Hepcidin is a low molecular weight, antimicrobial peptide hormone and was first discovered in human urine . It is produced by the liver as a firstline response to inflammatory reactions and high Fe concentrations . Hepcidin plays a fundamental role in the regulation of Fe metabolism , which is a part of foundational cellular functions and thus of vital importance. On the other hand, by participating in redox reactions leading to the production of reactive oxygen species , Fe also causes oxidative stress. Therefore, Fe has been regarded as a potentially toxic element to cells . Fe also plays an Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: washed in phosphate-buffered saline and incubated with a polymer horseradish peroxidase-conjugated secondary antibody for one hour. The sections were further incubated with Dako Liquid DAB Large-Volume Substrate-Chromogen System and counterstained with hematoxylin. Negative controls were included in all assays by replacing the rabbit anti-mouse hepcidin antibody with nonimmune rabbit antiserum. The immunostaining was evaluated using an Olympus BX-50 light microscope . The stain density was analyzed using the Image Pro-Plus 6.0 analysis system , and the level of hepcidin was measured as the integral optical density.", "Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically: Title: Gain-of-Function Research: Ethical Analysis", "Passage: were published in 2012. Advocates of these studies/publications argued that they would improve surveillance of H5N1 in nature and facilitate development of vaccines that might be needed to protect against pandemic strains of the virus. Critics questioned the validity of claims about such benefits and argued that the studies might facilitate creation of biological weapons agents that could kill millions, or possibly even billions, of people.", "Title: Estimating the number of infections and the impact of non-\nPassage: distribution and the initial growth rate of observed deaths. A shorter assumed serial interval results in Title: Estimating human-to-human transmissibility of hepatitis A virus in an outbreak at an elementary school in China, 2011\nPassage: than the above direct estimate. The shortness of MLE of serial interval is the consequence of many short pairs of infector-infectee reconstructed: One sample of the reconstructed transmission trees for the Hepatitis A outbreak is shown in the left panel of Fig 1. Within this sample tree, the reconstructed infector-infectee pairs have a mean of 7.7 days, which substantially reduces the overall pooled mean. In view of the large amount of infections being asymptomatic , the shortness of the serial interval of reconstructed infector-infectee pairs must have been due to the ignorance of contribution of asymptomatic infections. Hence we regard Title: Estimation in emerging epidemics: biases and remedies", "Passage: value which should be less than the true expected generation time, which is 15. Theory again predicts that the backward generation time should have mean 12.57, which is not far from what is observed. The variance of the true generation time is 75 and both variance estimates from the simulation samples tend to be much less, somewhat above 50 . This also leads to the useful conclusion that serial intervals are affected by the same \"contraction\" as generation times when ascertained \"backwards\", at least in the chosen parameter setting. Title: Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic", "Passage: interval is most sensitive to the mean exposed period, 1=s, and thus this is more accurately estimated. Although the parameter estimates from the three models are different, the estimated serial interval distributions corresponding to mean parameter estimates are all very similar , thus so are the mean serial intervals. The fit using N~4 is the best in terms of the mean likelihood.", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: Text: Globally, recent decades have witnessed a growing disjunction, a 'Valley of Death' 1,2 no less, between broadening strides in fundamental biomedical research and their incommensurate reach into the clinic. Plumbing work on research funding and development pipelines through recent changes in the structure of government funding, 2 new public and private joint ventures and specialist undergraduate and postgraduate courses now aim to incorporate pathways to translation at the earliest stages. Reflecting this shift, the number of biomedical research publications targeting 'translational' concepts has increased exponentially, up 1800% between 2003 and 2014 3 and continuing to rise rapidly up to Title: Globalization and Health: developing the journal to advance the field", "Passage: In the early years of the journal there was no clear preference for research articles . However from 2011 onwards, research articles accounted for over 50 % of the publications in the journal. Literature reviews were also favoured . Approximately 17 % of papers were classed as highly accessed by the journal's publisher, Bio-Med Central . Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: The number of articles increased exponentially over the period 1965-2017 . Approximately 60% of the articles have been published since 2000. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis", "Passage: The evolution of RCTs has been an enduring and continuing process . Since the 1970s the publication landscape for RCTs has exhibited an exponential growth. For example, a 1965-2001 bibliometric analysis of the literature identified 369 articles published in 1970 compared to 11,159 published in 2000 . The development of clinical trial registries , the exponential increase in journals publishing trial protocols, results and secondary studies, and growing support for data-sharing policies have created an open research environment of transparency and accountability. Furthermore, the publication of reporting guidelines have served to facilitate the transition between research and reporting to ensure", "Title: Host resilience to emerging coronaviruses\nPassage: Abstract: Recently, two coronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, have emerged to cause unusually severe respiratory disease in humans. Currently, there is a lack of effective antiviral treatment options or vaccine available. Given the severity of these outbreaks, and the possibility of additional zoonotic coronaviruses emerging in the near future, the exploration of different treatment strategies is necessary. Disease resilience is the ability of a given host to tolerate an infection, and to return to a state of health. This review focuses on exploring various host resilience mechanisms that could be exploited for treatment Title: Host resilience to emerging coronaviruses", "Passage: patients . By understanding risk factors for disease severity we can perhaps predict if a host may be nonresilient and tailor the treatment options appropriately. Title: Host resilience to emerging coronaviruses\nPassage: disease tolerant and other patients less tolerant to the viral infection. These factors can serve as a guide to new potential therapies for improved patient care. Title: Host resilience to emerging coronaviruses\nPassage: \u2022 Host resilience is the ability of a host to tolerate the effects of an infection and return to a state of health.", "Title: Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment\nPassage: Flow cytometry of propidium iodide-stained nuclei was performed as described previously . Briefly, PC-3 cells were seeded into 10-cm dishes at a density of 125 0000 cells/well. 24h later, cells were treated with compounds 14 at 100\u03bcM as indicated above. DNA content was determined by flow cytometry using a LSRII SORP machine. Rates of cells death were then measured using FlowJo software . 10 6 PC3 cells were inoculated in the flank region of 2-week-old athymic male mice . Tumors were measured weekly and their volume was calculated by the formula length\u00d7width\u00d7depth\u00d70.5236. When tumors reached 100 mm 3 , mice Title: Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment", "Passage: Cells were transiently transfected the day after seeding with Hsp27 deletion or phosphorylation mutant plasmids as described above, or treated with 14. Transfected cells were then treated with docetaxel in serum-free media for 24h. Cell viability was assessed using 3--2, 5-diphenyl tetrazolium bromide assay for REG, PC-3 and PC-3 RD cells, as previously described . Each assay was performed in triplicate. www.impactjournals.com/oncotarget Title: Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment", "Passage: The human androgen-independent cell line PC-3 were maintained in DMEM media supplemented with 10% fetal bovine serum . The rat colon carcinoma cancer cell line REG was provided by Dr Carmen Garrido and maintained in F10 medium supplemented with 10% FBS. The Human Embryonic Kidney cell line HEK293T was maintained in Dulbecco's Modified Eagle's Medium , supplemented with 10% FBS. All cell lines were cultivated at 37\u00b0C in 5% CO 2 . PC-3DR-docetaxel resistant cell line was kindly provided by Dr Martin Gleave and was maintained in culture as previously described. Title: CXCL9 promotes prostate cancer progression through inhibition of cytokines from T cells", "Passage: 3 weeks to construct the prostate cancer model. The mice were anesthetized by 10% chloral hydrate solution , and then the blood samples were collected. Then the mice were sacrificed by cervical dislocation, and the prostate tissues were collected and stored. Animal experiments were approved by the Medical Ethics Committee of Linyi People's Hospital.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: Viral vector-based influenza vaccines", "Passage: viral vectors can easily be propagated to high virus titers and it is relatively easy to insert genes encoding antigens of choice into the vector. Viral vector technology also allows the production of modified influenza viral antigens in vivo. These modifications can improve the immunogenicity of the influenza viral proteins or alter the specificity of the immune response. In this review, we discuss reports on vectored influenza vaccines and discuss their advantages and disadvantages. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: helps sustain a durable memory immune response, even augmenting the selection of higher affinity antibody secreting cells. The enhanced memory response is in part linked to the intrinsic augmentation of immunity induced by the vector. Thus, for weaker antigens typical of HA, vectored vaccines have the capacity to overcome real limitations in achieving robust and durable protection.", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Childhood pneumonia can also lead to significant morbidity and chronic disease. Early life pneumonia can impair longterm lung health by decreasing lung function . Severe or recurrent pneumonia can have a worse effect on lung function; increasing evidence suggests that chronic obstructive pulmonary disease might be related to early childhood pneumonia . A meta-analysis of the risk of long-term outcomes after childhood pneumonia categorized chronic respiratory sequelae into major and minor groups . The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Childhood pneumonia and clinically severe disease result from a complex interaction of host and environmental risk factors . Because of the effectiveness of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination for prevention of radiologic and clinical pneumonia, incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases Title: The impact of respiratory viruses on lung health after preterm birth", "Passage: hospitalisation for another respiratory illnesses as well as a more than 4-fold increased risk of subsequent asthma . Title: Risk factors for severe acute lower respiratory infections in children \u2013 a systematic review and meta-analysis\nPassage: Pneumonia is one of the leading causes of morbidity and mortality globally in young children aged below five years . It is estimated that approximately 156 million cases of pneumonia occur annually in young children, resulting in approximately 1.4 million deaths . Over the past two decades, there were several attempts to investigate an association between various risk factors and pneumonia in young children, but no systematic reviews of published literature assessed the strength of association between the suspected risk factors and pneumonia. In this study, we aimed to assess the quality of available evidence and present summary estimates of", "Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak\nPassage: Between September 10, 2009 and August 29, 2011, 71,865 body temperatures were electronically recorded by the automatic data logging system and met the inclusion criteria . During the study period, there were 110,465 visits to the emergency department, 37 % of which resulted in admission . Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak", "Passage: The mean body temperature was 98.1\u00b0F with a standard deviation of 1.1\u00b0F . The median body temperature was 98.0\u00b0F with an interquartile range of 97.4-98.7\u00b0F . These values are consistent with previous reports is not the mean human body temperature, despite widespread belief ). Overall, 2073 fevers were observed, constituting 2.6 % of the temperature recordings . A mean of 1.0 fevers was measured per thermometer each day . Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak", "Passage: this period : 1.08, range, 1-5), with exceptions for general maintenance. Thermometers were checked, time-stamped measurements were collected, and maintenance was performed on a roughly biweekly basis. Three thermometers were located at triage stations and one was located on a rolling unit. The data-logging thermometers were used as a surrogate to investigate the capabilities of real-time data reporting with networked wireless thermometers. Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak", "Passage: Additional Figure 1 presents the results of applying a Bayesian outbreak detection algorithm to the number of fevers measured in the ED per thermometer. The light blue and dark blue areas show the weekly and daily rates of fevers, respectively. For example, data from the first week of August 2011 show that around 5 fevers were measured per thermometer. The outbreak detection algorithm produces an epidemic threshold that is used to judge whether an outbreak is detected. When the observed fever rates exceed this threshold, an alarm is declared . Using fever rates from the Boston ED, the algorithm successfully", "Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1\nPassage: Text: Without specific interventions, the rate of HIV-1 mother-tochild transmission is approximately 15-45% . UNAIDS estimates that last year alone, more than 400,000 children were infected worldwide, mostly through MTCT and 90% of them lived in sub-Saharan Africa. In the most heavilyaffected countries, such as Zimbabwe, HIV-1 is responsible for one third of all deaths among children under the age of five. MTCT of HIV-1 can occur during pregnancy , delivery or breastfeeding . High maternal viral load, low CD4 cells count, vaginal delivery, low gestational age have all been identified as independent factors associated with MTCT of HIV-1 . Title: HIV testing, test results and factors influencing among infants born to HIV positive mothers in public hospitals of Mekelle City, North Ethiopia: a cross-sectional study", "Passage: The prevalence of HIV among exposed infants can reach up to 45% if left without PMTCT interventions. Nearly two-third of pregnant women living with HIV in the Middle East and North Africa passed the virus onto their infants in the year 2015 alone 10, 11] . In Ethiopia, vertical transmission, which accounted for more than 90% of pediatric HIV, is a very critical issue. Accordingly, HIV related estimates and projections showed that the national estimate of MTCT rate was 25% in 2013 and 17% in 2015. This high magnitude makes HIV/AIDS one of the top priorities of the Health Sector Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: In 2010, UNAIDS estimates that 390,000 children acquired HIV-1-infection worldwide mostly through mother-to-child transmission . Overall transmission rates in the absence of any intervention vary from 12 to 42%. Although antiretroviral therapy can reduce MTCT to as low as 2% , limited access to timely diagnostics and drugs in resource-poor settings blunts the potential impact of this strategy. A better understanding of the mechanisms acting in MTCT of HIV-1 is crucial for the design of interventions other than ART for transmission prevention. Title: HIV testing, test results and factors influencing among infants born to HIV positive mothers in public hospitals of Mekelle City, North Ethiopia: a cross-sectional study", "Passage: Although timely HIV testing of infants is not yet optimal, some strategies and solutions have proven successful, including community-based interventions and support and education of mothers. The Joint United Nations Program on HIV/AIDS 2016-2021 strategy set about ten targets to end the AIDS epidemic by 2030; one of the targets is to make new HIV infections among children zero and improve the health and wellbeing of mothers. The global plan to eliminate new HIV infections among children and improve the health of mothers targets to reduce the MTCT rate to less than 5% among breast feeding population and to less", "Title: How necessary is a fast testkit for mitigation of pandemic flu?\nPassage: Contact tracing is a non-pharmaceutical social distancing measure for limiting the spread of influenza by identifying people who may have come into contact with an infected person, and giving them prophylaxis or issuing them with quarantine orders. It has been shown theoretically that through contact tracing, major outbreaks can be reduced significantly at a small additional cost . We divided the contacts of each patient into one of the following three categories: household, workplace and friends. When contact tracing for a class has been activated, i.e. the index case is being tested positive for pandemic influenza, all the contacts in Title: The Effectiveness of Contact Tracing in Emerging Epidemics", "Passage: Capacity problems may reduce the effectiveness of iterative tracing if effort is directed towards secondary contactees prior to primary contactees; on the other hand, if not quarantine but vaccination is applied, it might be worthwhile to traced contactees of contactees even without diagnostic tests . Title: The Effectiveness of Contact Tracing in Emerging Epidemics\nPassage: A relatively easy way to increase the proportion of traced contacts for respiratory pathogens like influenza might be quarantine of households. This can be effective if households are the prime location for spread of the infection; specific models taking into account the contact structures within and between households will be better-suited to study this strategy. Title: The Effectiveness of Contact Tracing in Emerging Epidemics\nPassage: However, if the latent period is short, as seen for influenza and possibly FMD, quarantine will occur too late to prevent all infections and more contacts need to be traced.", "Title: Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections\nPassage: disease . The compliment subunit C5a plays a role in neutrophil recruitment to the mouse lung following IAV infection and may be a potent inducer of hyperoxia-mediated lung injury via recruitment of macrophages, neutrophils, and lymphocytes, and increased expression of IL-6, TNF-\u03b1, and MCP-1 occurs . Furthermore, C5a has been shown to increase TGF-\u03b21 in primary human small airway epithelial cells, which could then contribute to the development of fibrosis . Thus, multiple factors could lead to the accumulation of C5a, which could induce inflammation in the lungs of preterm infants. Some of these factors have been proposed targets to Title: Host resilience to emerging coronaviruses", "Passage: Corticosteroids are broadly immunosuppressive and have many physiological effects . Several recent studies have suggested that other compounds could be useful in increasing host resilience to viral lung infections. A recent paper demonstrates that topoisomerase I can protect against inflammation-induced death from a variety of viral infections including IAV . Blockade of C5a complement signaling has also been suggested as a possible option in decreasing inflammation during IAV infection . Other immunomodulators include celecoxib, mesalazine and eritoran . Another class of drugs that have been suggested are statins. They act to stabilize the activation of aspects of the innate immune Title: Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application*", "Passage: T he complement system is a pivotal component of innate immune system and bridge of the innate and adaptive immune responses. However, once dysregulated, it can turn against host cells and is involved in numerous diseases and pathologic conditions such as inflammatory diseases, autoimmune diseases, neurodegenerative diseases, and infectious diseases . Complement activation products such as C5a play an important role in mediating proinflammatory activity and regulating modulatory signals . Thus, regulation of complement activation is a promising treatment strategy . Regulating C5a or C5aR has proven beneficial in animal models of transplantation, sepsis, arthritis, and cancer . DOI: 10.1097/CCM.0000000000002950 Title: New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System", "Passage: On a cellular level, it has been shown that C5a effectively interacts with cells and modulates their apoptosis rate. Interestingly, the effects on programmed cell death seem to be cell dependent, with a higher rate of apoptosis in thymocytes but decreased apoptosis in neutrophils . Overall, the C5ainduced changes point toward an enhanced susceptibility toward infections, as well as to a prolonged presence of neutrophils resulting in an exaggerated inflammatory response and host damage.", "Title: Modeling the impact of quarantine during an outbreak of Ebola virus disease\nPassage: To show that all solutions of the model The result below follows from the above analyses. Title: Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning\nPassage: for showing the effect of mixing in school on earlier transmission to households. The island's school was closed on 31 January. 60 McVernon et al. Title: The Model Repository of the Models of Infectious Disease Agent Study\nPassage: . Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: the fact that in all waves and places the BRT model found the spatial autocorrelation term to have the highest rank of influence. As expected, the relative influence of the autocorrelation term at the national level was higher than at the delta levels . In the GLMM models we found the Akaike Information Criterion using the entire set of 14 variables to be much lower than the AICs of a GLMM model without fixed effects. This indicated that though clustering effects were significant, our theory driven predictor variables improved model performance.", "Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity\nPassage: The colectomy rate in our study was found to be 7.7%, while the colectomy rate in hospitalized SUC patients reported by the West China Hospital is 17.9%, both are lower than the 20%-40% reported in United Kingdom . Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity\nPassage: significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. Total proctocolectomy with ileal pouch-anal anastomosis was the most commonly employed operation. Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity\nPassage: mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis. Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity", "Passage: incidence of pouchitis ranged from 7.7% to 50% as reviewed in this study. According to our data, the short-term mortality rate of SUC is 0.8%, lower than the 1.2% reported in western countries . These results are consistent with that reported by Wang et al , who observed a relatively milder clinical course and lower rate of complications in Chinese UC patients. UC is associated with an increased risk of colorectal cancer. The severity of histological inflammation correlates with colorectal cancer risk . The incidence of colorectal cancer among SUC patients is 0.13% in our study, lower than the values", "Title: The 1918 Influenza Pandemic: Looking Back, Looking Forward\nPassage: In commemoration of the centennial of the 1918 pandemic, the American Journal of Epidemiology has convened a collection of 12 articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge today. Five of the 12 articles touch on the origins of the 1918 pandemic virus, addressing the role of swine as mixing vessels in this and other pandemic events , the age-specific mortality patterns of the pandemic , and prior population immunity . Others include reports on geographic and social heterogeneities in the pandemic Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: The early 20th century was a time of dramatic changes in human use of domestic animals . After centuries of influenza epizootics in equines, the 20th century marked a rapid decline in use of horses for urban transport and farm work. Just as declining densities of horses were breaking the episodic cycles of equine influenza in urban areas, a trend toward high-intensity livestock production was underway . In addition to representing one of the greatest disease events in human history, the Spanish flu pandemic may also mark a turning point in the ecology of influenza and the increasing importance of Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: However, to our knowledge, there is no evidence of sustained onward transmission of the 1918 pandemic virus outside of North America, where the virus sustained long-term circulation in pigs and became established as the \"classical\" H1N1 swine influenza virus lineage , which continues to circulate in North American and has been introduced into Asian swine. Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: Overall, the most parsimonious explanation is that the genes of the 1918 virus transmitted largely from birds to humans at the start of the pandemic, and from humans to swine once the pandemic was widespread in humans, with no role played by swine in the origins of the human pandemic . In addition to Koen, there is a reference to an infection with influenzalike disease in swine near the China-Russia border during the second global wave of the pandemic during October 1918 and an independent description of influenza in European swine in 1918 by Altmann Aladar, a Hungarian veterinarian .", "Title: Unified feature association networks through integration of transcriptomic and proteomic data\nPassage: Network centrality in biological networks is an indicator of the importance of the node to the function of the network . Pathways with higher centrality in host response networks may be more important to the host response and/or may be more coordinated in terms of their activity. To that end, the centrality of features in KEGG pathways was compared between each network to identify functions that may have higher or lower centrality in an antibody vs. receptor-mediated network. We used betweenness, the number of paths through a network that pass through the gene in question, as a measure of centrality. Title: Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations", "Passage: Multiple measures can improve the confidence in performance evaluation. We calculated five measures to evaluate the perfor-mance of features and TS prediction models from cross-validations. To compare the five measures, we computed the Pearson correlation and mutual information between every pair of the five measures across all 133 individual feature-based classifiers . Pearson correlation is only sensitive to a linear relationship between two variables while mutual information is capable of detecting non-linear relationships. We found that AUC and DD had the best concordance according to mutual information and the third best concordance according to the Pearson correlation. Both measures consider Title: Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations", "Passage: Next, we were interested in testing the predictive power of sequence and structure features. The ''sequence features'' model contained features calculated from sequence information only, while the ''structure features'' model had features derived from the protein crystal structure. The ''all features'' model combined sequence and structure features. The performance of the ''all features'' model was slightly better than that of the ''structure features'' model, while the ''structure features'' model performed better than the ''sequence features'' model . This suggests that structure-based features have higher predictive power than sequence-based features in differentiating TS mutations from neutral mutations. Nevertheless, the results demonstrated Title: Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations", "Passage: As shown in Figure 6A , the ROC curve of the ''all features'' model is biphasic. True positive rates are three-fold of false positive rates when applying thresholds greater than 0.5, while true positive rates are less than two-fold of false positive rates when applying thresholds less than 0.5. Although the AUC value is slightly lower than those of leave-one protein-out , the lower left portion of the ROC curve is comparable with those, suggesting our top-ranked predictions are particularly accurate. We further plotted precision-recall curves to evaluate the performance of the ''all features'' model . A 50% precision is", "Title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985\u20132008\nPassage: Despite the availability of safe and effective antibiotics and vaccines for treatment and prevention, pneumonia is a leading cause of death worldwide and the leading infectious disease killer . Pneumonia is the single leading cause of death globally among children under 5 years of age accounting for approximately 2 million deaths annually . Children in developing countries have an estimated 0.29 episodes of pneumonia per person-year, compared with 0.05 episodes per person-year in developed countries . Title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985\u20132008", "Passage: September 2009 . In addition, Hong Kong SAR recommends seasonal influenza vaccine use in high risk groups. Vaccine clinical trials in other countries have estimated that 21% of radiologically confirmed pneumonia is caused by Hib and 36% by pneumococcus ; over 10% of hospitalized pneumonia in children in nearby Thailand are due to influenza . Studies within China have suggested that Hib and pneumococcus are common causes of pneumonia in children , suggesting that widespread use of these two vaccines, as well as influenza vaccine, could reduce the incidence and mortality of pneumonia in China. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: A systematic review of etiology studies prior to availability of new conjugate vaccines confirmed S. pneumoniae and H. influenzae type B as the most important bacterial causes of pneumonia, with Staphylococcus aureus and Klebsiella pneumoniae associated with some severe cases. Respiratory syncytial virus was the leading viral cause, identified in 15-40% of pneumonia cases, followed by influenza A and B, parainfluenza, human metapneumovirus and adenovirus . Title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985\u20132008", "Passage: Better access to proven public health interventions, including vaccines, is needed in the public sector in China. Vaccines against Haemophilus influenzae type b , Streptococcus pneumoniae, and influenza are not part of routine childhood vaccination programs in many countries worldwide ; none of these vaccines are included in the routine childhood immunization schedule in mainland China. However, Hib and influenza vaccines are commonly available in many parts of China through vaccination clinics, and Hong Kong SAR is the first region in China, as well as Asia, where pneumococcal conjugate vaccine will be included in their routine childhood immunization program starting", "Title: Quantifying social distancing arising from pandemic influenza\nPassage: social distancing. Title: Quantifying social distancing arising from pandemic influenza\nPassage: thus discouraging people from getting out and circulating in the wider population . Title: Estimating the number of infections and the impact of non-\nPassage: Social distancing Avoid social interaction wherever possible Title: Quantifying social distancing arising from pandemic influenza\nPassage: F wa\u015d R\u00f0F\u00deZ 0:95G0:04\u00f0Gs:e:\u00de.", "Title: Dating the time of viral subtype divergence\nPassage: The study here focuses on influenza, although the techniques are readily applied to other rapidly evolving organisms. Influenza has three types, A, B and C, classified based on serological analysis. To date, only type A sequences have been demonstrably associated with global pandemics . Since modern surveillance began in the 1930s, type B has only been responsible for mild epidemics while type C has been nearly asymptomatic in human infection. Several subtypes of A, notably H1N1 and H3N2, are currently co-circulating in the human population. As the H1N1 and H3N2 subtypes may be as divergent from each other as they Title: Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types", "Passage: At the conclusion of this analysis of all available HRV VP1 sequences, totals of 77 HRV-A types, 29 HRV-B and 51 HRV-C types have been listed in full in Tables S1 and S2). Novel strains of HRV were classified based on date of submission to the Picornaviridae Study Group, rather than the earliest isolated strain. Title: Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types\nPassage: As described above, their current classification can incorporate phylogenetic data and any available information on neutralization properties in addition to VP1 distances. Combined, these may potentially resolve any remaining uncertainties over type assignments. Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: There are 3 main types of circulating influenza viruses in the world: A, B, and C. Influenza viruses are enveloped negative-strand RNA viruses with segmented genomes . Of its two genera, one includes influenza A and B viruses, and the other influenza C virus. Type A influenza viruses are subtyped based on 16 known hemagglutinin and nine neuraminidase subtypes that exist in wild birds and provide a source of viral HA and NA subtypes antigenically novel to humans. The subtypes are further classified according to the combinations of virus surface proteins, abbreviated as H1-H16 and N1-N9 , starting with the", "Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,\nPassage: We found that daily air travel volume positively correlates with imported-and-reported case counts of SARS-CoV-2 infection among high surveillance locations . We noted that increasing flight volume by 31 passengers/day is associated with 1 additional expected imported-and-reported case. In addition, Singapore and India lie above the 95% PI in our model; Singapore had 12 more imported-and-reported cases than expected and India had 3 more than expected. Thailand has a relatively high air travel volume compared with other locations, but it lies below the 95% PI, reporting 16 fewer imported-and-reported cases than expected under the model. Indonesia lies below the PI Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,", "Passage: The model requires data on imported-and-reported cases of SARS-CoV-2 infection, daily air travel volume, and surveillance capacity. We obtained data on imported-and-reported cases aggregated by destination from the World Health Organization technical report issued February 4, 2020 . We assumed a case count of 0 for locations not listed. We used February 4 as the cutoff for cumulative imported-and-reported case counts because exported cases from Hubei Province dropped rapidly after this date , likely because of travel restrictions for the province implement on January 23. We defined imported-and-reported cases as those with known travel history from China; of those, 83% Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,", "Passage: Most cases imported to other locations have been linked to recent travel history from China , suggesting that air travel plays a major role in exportation of cases to locations outside of China. To prevent other cities and countries from becoming epicenters of the SARS-CoV-2 epidemic, substantial targeted public health interventions are required to detect cases and control local spread of the virus. We collected estimates of air travel volume from Wuhan to 194 international destinations. We then identified 49 countries that had a score of >49.2/100 on category 2, Early Detection and Reporting of Epidemics of Potential International Concern, Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,", "Passage: To identify locations reporting fewer than predicted imported SARS-CoV-2 infected cases, we fit a model to data from 49 locations outside mainland China with high surveillance capacity according to the GHS Index . Among these, 17 had high travel connectivity to Wuhan and 32 have low connectivity to Wuhan. We considered locations to be countries without any position on territorial claims. We performed a Poisson regression by using the cumulative number of imported-and-reported SARS-CoV-2 cases in these 49 countries and the estimated number of daily airline passengers from the Wuhan airport. We then compared predictions from this model with imported-and-reported", "Title: Assessing global preparedness for the next pandemic: development and application of an Epidemic Preparedness Index\nPassage: National preparedness to detect emerging or epidemic-prone diseases requires adequate financial resources and investment in public health systems. 16 The same is true of response: a large body of evidence points to a direct link between the adequacy of health financing and key metrics associated with effective response, including the quality of clinical care and health outcomes. 17 During acute public health emergencies, health ministries as well as local government units may be required to rapidly scale up surveillance and health provision activities. This can lead to rapidly mounting costs, especially for personnel and consumables such as personal protective equipment Title: Assessing global preparedness for the next pandemic: development and application of an Epidemic Preparedness Index", "Passage: Effective public health systems are vital for early detection, mitigation and management of infectious disease outbreaks. Early detection requires robust surveillance and effective outbreak investigation capabilities for rapidly identifying, characterising and tracking emerging infectious diseases. 10 This capacity requires effective health institutions with capacity to access and monitor the entirety of the geography and population. Once an epidemic is underway, the healthcare and public health systems must be able to identify, investigate, monitor and manage abrupt surges in cases through the mobilisation of personnel and resources. Health systems must be able to manage the clinical care for infected persons, and Title: Assessing global preparedness for the next pandemic: development and application of an Epidemic Preparedness Index", "Passage: A conceptual framework for epidemic preparedness and response Epidemic preparedness reflects the capacity of institutions-public health authorities, health systems and emergency response bodies-to detect, report and respond to outbreaks. Government institutions must detect and assess potentially consequential outbreak events, report outbreaks and their causes to relevant national and international organisations and networks, and respond with measures to reduce the health, societal and economic impacts of outbreaks. 5 7 While preparedness for public health emergencies is typically considered in terms of surveillance, response and health capacity, these functions in turn rely on a broader set of institutional, financial and infrastructural factors. Title: Assessing global preparedness for the next pandemic: development and application of an Epidemic Preparedness Index\nPassage: and vaccines, which can be difficult to sustain without adequate resources.", "Title: Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity\nPassage: The only positive sample to HPIV2 was collected during winter. HPIV1 and HPIV3 detection occurred mainly in late winter and spring. Similar results were reported showing this virus presence in samples collected in spring, autumn and winter. According to literature, HPIV3 are the most frequent viruses from this family, being type 1 and 2 viruses barely detected or even detected, which shows agreement with obtained results to literature data. Title: Seasonal distribution of active systemic lupus erythematosus and its correlation with meteorological factors\nPassage: low incidence in the summer. Title: Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity", "Passage: This study was conducted at the Genomic Studies The total respiratory infections were detected mainly in winter, spring and summer of 2004, and autumn and winter of 2005, as showed in Figure 1A , which also demonstrate the seasonal distribution of the detected respiratory viruses. Title: Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity\nPassage: FLUA and FLUB were detected in few samples; however, these samples were collected during autumn and winter, agreeing to previous studies that showed Inlfuenza outbreaks occurring between late summer and early winter .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first known MERS human-to-human transmission event was one characterized by acute LRT disease in a healthcare setting in Jordan. In stark contrast, a sero-survey of HCW who were sometimes in close and prolonged contact with the first, fatal MERS-CoV case in 2012 , found none of the HCW had seroconverted four months later, despite an absence of eye protection and variable compliance with required PPE standards . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: Researches showed that the R 0 of severe acute respiratory syndrome was about 2.7-3.4 or 2-4 in Hong Kong, China . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 . The transmissibility of the Middle East respiratory syndrome is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 , with the inter-human transmissibility of the disease was about Title: The Failure of R (0)", "Passage: While the first factor may be fairly uniform across outbreaks, the second may depend significantly on context, varying both within and among populations. The problem with the SARS estimates stems from the mass-action assumption of compartmental models; that is, that all susceptible individuals are equally likely to become infected. When this assumption does not hold, the models may yield inaccurate estimates or estimates that do not apply to all populations. R 0 estimates for SARS in the field were based largely on outbreak data from a hospital and a crowded apartment building, with anomalously high rates of close contacts among Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Secondly, the R0, the basic reproduction number, is correctly described as the average number of infections each case causes. But it lacks two key ideas: 1) the 0 after the R implies the native state, which is a fully susceptible population and without any control measures. R is the effectiive number and can include the impact of control measures. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: In this study, we used the R 0 to assess the transmissibility of the SARS-CoV-2. Commonly, R 0 was defined as the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population . If R 0 > 1, the outbreak will occur. If R 0 < 1, the outbreak will toward an end. In this study, R 0 was deduced from the RP model by the next generation matrix approach . The multiple of the transmissibility of A P to that of I P .", "Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: Among the 148 swabs initially negative for influenza because not previously tested for any other viruses, the study found an etiology for 95 swabs. In total, only 53 swabs, representing 24% of the sample, remained without etiology with negative multiplex PCR results all along the year. Multiple hypotheses can explain this result: a poor quality of swabs, preventing from identifying a pathogen, noninfectious causes or other pathogens not included in the multiplex PCR. However, we couldn't test the negative swabs for RNAse P, a marker of human cells, which could provide a modicum of assurance that the swab contained human Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: Of the 29 swabs received, 18 had a corresponding research swab that was positive for a respiratory pathogen. Seven corresponding self-swabs were concordant with the positive research swabs for influenza, and eight corresponding self-swabs were concordant with the research swab for noninfluenza pathogens . The kappa statistic between research and self-swab was 0.84. There were no differences in demographic variables, including education level or days between drop-off and receipt of swabs, among participants whose self-and research-staff obtained swabs correlated versus those whose swabs did not correlate . Of the self-swab samples that had a corresponding positive research swab, the longest Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Among the 250 randomly-selected swabs, 26 were not available anymore as they were sent to Influenza Reference Center for confirmation and characterization of the pathogenic agent. According to the sensitivity of the assay two samples could be discordant results between Influenza PCR initially realized and Multiplex PCR. Thus they were deleted from the analysis: one is positive for Influenza in singleplex and negative for all tested pathogens in multiplex and one is positive for Influenza in singleplex and positive for PIV2 in multiplex. In total, 222 analyses were considered. Moreover, 53 samples were negative for all analyzed respiratory pathogens and Title: Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden", "Passage: 2 than -5 laboratory results were not linked to symptoms reported. On the other hand, 272 sick reports could not be merged to nasal swabs. Apart from the same issue of timing, this fact might also be explained by certain symptoms reported. The absence of a nasal sample correlates well with the presence of vomiting and the absence of runny nose. Further details on specimen results can be found in our Eurosurveillance paper . Briefly, when analyzing the seasonality, we found that the peak in the number of returned swabs was reached in the last week of September 2011, but", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: SARS-CoV that includes the split orf8b , civet SARS-CoV , two bat SARS-related-CoV containing full-length orf8 , 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5 ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: subunit of 2019-nCoV shares around 70% identity to that of the two bat SARS-like CoVs and human SARS-CoV ), the core domain of RBD are highly conserved ). Most of the amino acid differences of RBD are located in the external subdomain, which is responsible for the direct interaction with the host receptor. Further investigation of this soluble variable external subdomain region will reveal its receptor usage, interspecies transmission and pathogenesis. Unlike 2019-nCoV and human SARS-CoV, most known bat SARSr-CoVs have two stretches of deletions in the spike receptor binding domain when compared with that of human SARS-CoV. But some Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first WHO case definition defined probable cases of MERS based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract involvement. It also included roles for contact with a probable or confirmed case or for travel or residence within the Arabian Peninsula. If strictly adhered to, only the severe syndrome would be subject to laboratory testing, which was the paradigm early on . From July 2013, the revised WHO case definition included the importance of seeking out and understanding the role of asymptomatic cases and from June 2014, the WHO definition more Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: clearly stated that a confirmed case included any person whose sample was RT-PCR positive for MERS-CoV, or who produced a seroconversion, irrespective of clinical signs and symptoms. Apart from the WHO and the KSA Ministry of Health reports, asymptomatic or subclinical cases of MERS-CoV infection were documented in the scientific literature although not always as often as occurred early on . The KSA definition of a case became more strict on 13 th May 2014, relying on the presence of both clinical features and laboratory confirmation . Testing of asymptomatic people was recommended against from December 2014 , reinforced by Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: As a group, HCWs comprised 16 % of MERS cases in the KSA and South Korea. It is apparent that the weekly proportion of infected HCWs increases alongside each steep rise in overall detections . In May 2013, the WHO published guidelines for IPC during care of probable or confirmed cases of MERS-CoV infection in a healthcare setting . This is explainable because to date, each case rise has been intimately associated with healthcare-facility related outbreaks . These rises in MERS-CoV detections can decrease the average age during each event because HCWs are usually younger than inpatients with MERS. Healthcare Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: case detection and management. Data collected included demographics, history of recent travel to affected areas, close contact with a probable or confirmed COVID-19 case, underlying conditions, signs and symptoms of disease at onset, type of specimens from which the virus was detected, and clinical outcome. The WHO case definition was adopted for surveillance: a confirmed case was a person with laboratory confirmation of SARS-CoV-2 infection , irrespective of clinical signs and symptoms, whereas a probable case was a suspect case for whom testing for SARS-CoV-2 was inconclusive or positive using a pan-coronavirus assay . By 31 January 2020, 47 laboratories", "Title: Quantifying social distancing arising from pandemic influenza\nPassage: the build-up of herd immunity and possibly pre-existing immunity. Title: Quantifying social distancing arising from pandemic influenza\nPassage: We have assumed an 'all or nothing' model of prior immunity, meaning that a fraction of individuals were totally protected from infection during the pandemic period. The main alternative model of prior immunity is that a fraction of the population is partially immune, having a lower risk of infection. Under some circumstances, there will be material differences between the behaviour of these prior immunity models: if R 0 is very large, all susceptibles, whether fully or partially immune, will inevitably be infected; alternatively, if there is assortative mixing between classes of susceptibles, fully susceptibles will be overrepresented during the early Title: Human mobility and the worldwide impact of intentional localized highly pathogenic virus release", "Passage: The case of 20% immunity in population as a result of the vaccination campaign that successfully eradicated smallpox in the late seventies, was also considered. The results for the UK and the top 20 affected countries in each scenario, 14 days after the attack, are summarized in Fig 9 and Fig 10 for the two seeding possibilities considered. As expected, in both cases, immunity is able to reduce both the number of cases within each country and the respective outbreak probability, but is not sufficient to prevent the infection from spreading into other countries. Title: Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects", "Passage: Following mass vaccination with 100% coverage, population susceptibility, X, quickly increases over time in the presence of high migration rates and short-lived vaccine efficacy . Even with a hypothetical perfect vaccine that retains complete protection indefinitely, high migration rates can drive population susceptibility near 100% within 9-10 years . Between three primary drivers causing herd immunity to wane, namely migration, waning efficacy, and demographic turnover through births and deaths, we find that the first two are substantially more influential than either the birth or death rate, which are each typically much slower processes. As compared to rates of birth and", "Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: syndrome such as high blood pressure. Macrophage activation syndrome could also lead to acute necrotic brain injury. However, it is associated to high ferritin and low triglycerides at the time of the encephalopathy, other multisystemic injuries, typical neuropathological findings, and recurrence over time, which were not noted in our patient . Parvovirus B19 has been described to cause encephalopathy in sickle cell patients. It is associated with aplastic anemia. It caused punctate areas of hemorrhages in the basal ganglia, periventricular white matter, and mainly along the posterior parietal cortex. This was attributed to parvovirus B19-induced vasculitis . In our patient, Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: Several differential diagnoses of acute encephalopathy in a patient with sickle cell anemia can be considered. An infectious encephalitis, including herpes encephalitis, was ruled out by blood and CSF bacterial and viral cultures and negative HSV I/ II PCR. Nasopharyngeal aspirate was negative for viruses. Some infections have been previously associated with necrotizing encephalitis such as Influenza A . SCD patients are prone to ischemic or hemorrhagic strokes . Primary hemorrhagic stroke is uncommon in pediatric SCD. Most cases were from adults and have been described in the context of previous ischemic stroke, aneurysms, low hemoglobin, acute chest syndrome, and Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: there was no sign of aplasia or any neuroradiological finding of parvovirus B19 infection. Finally, acute encephalitis has been observed in SCD patients in the context of arterial hypoxemia from fat embolism, pulmonary embolism, sudden anemia, or acute chest syndrome due to pneumonia . This was ruled out as the patient did not have clinical or radiological signs of acute chest syndrome or embolism and there was no arterial hypoxemia. Title: MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice", "Passage: Japanese encephalitis virus is the most prevalent cause of viral encephalitis worldwide. More than 67,900 cases of JE are reported annually, among which approximately 30% are fatal and 50% suffer from permanent neuropsychiatric sequelae . JEV infection causes devastating and fatal neuroinflammation characterized by neuronal destruction accompanied with intense microgliosis, strogliosis, and production of various inflammatory cytokines . Neurons can be destroyed directly by JEV infection and indirectly by inflammation mediated cytotoxicity . Then the massive neuronal death contributes to the progression and deterioration of Japanese encephalitis .", "Title: Early responses to H7N9 in southern Mainland China\nPassage: random number. Three thousand and fifty-four telephone numbers were dialled, of which 1082 gave interviews, and 1972 refused to participate . A further 32 gave incomplete responses , 39 were deleted as they had not heard of H7N9 or were out of the age quota group, leaving an eligible 1011 participants. Response rates compare positively to analogous public surveys on swine flu . Table 1 breaks down participants by age, sex and occupation, comparing these categories with wider Shanghai data . Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")", "Passage: Following ethical approval by the relevant University ethics boards in London and Malaysia, data was collected from a total of 328 respondents . A paper version of the questionnaire was distributed in Malaysia, with students recruiting 180 respondents from their own classes, and community members from residential areas and local offices in Kuala Lumpur , 59% female)). Response rate was generally good, with 180 out of 200 approached to participate completing the questionnaire. In Europe, data was collected between 30 th April and 6 th May 2009 from 158 respondents via an online questionnaire in English or Portuguese, linked to Title: Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study", "Passage: Sample size determination. We estimated that a sample of at least 500 was required to achieve 80% power at an a = 0.05 to reject a model of the specified complexity if the model fit index Root Mean Square Error of Approximation exceeded 0.08 . To allow for a response rate ,60% in the follow-up and the baseline surveys, we need to target at least 1,389 subjects in the baseline survey. Title: Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults\nPassage: binomial confidence interval of the true response rate will range from 0.057 to 0.437. Table 6 .1 gives the probabilities of observing 0 or at least 2 responses over a range of underlying response rates. For example, if the true response rate at a particular time point is 0.20, then there is a probability of 0.988 to observe at least one response and a probability of 0.931 to observe at least two responses among the 20 vaccinees.", "Title: Jun\u00edn virus induces autophagy in human A549 cells\nPassage: the Candid#1 vaccine. Title: Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors\nPassage: Currently, the only clinically successful anti-arenaviral vaccine is the anti-JUNV Candid #1 strain, which is currently manufactured by the Argentinian government but is not being considered for large-scale use due to its limited target population as only Argentina is endemic for JUNV infection. To generate Candid #1, a human viral isolate was used to passage twice in guinea pigs followed by additional passages in suckling mice and cell cultures . A number of unique mutations in Candid #1 were originally thought to attenuate Candid #1 compared to its parental WT strain , and one such mutation was consistently found to Title: Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors", "Passage: of other arenaviral vaccines. However, they may be limited to the JUNV vaccine for several reasons. While the IFN1 pathway pathway and subsequent T-cell response have been found to be critical in controlling arenaviral infection in mice , arenaviral-associated immunosuppression results in limited T-cell responses . Furthermore, the JUNV GP has been found to contain fewer glycans than the GPs from other mammarenaviruses , and glycan residues on the glycan-rich LASV GP has been shown to promote neutralization antibody evasion . This is strengthened by recent observations that anti-JUNV antibodies from infected patients can neutralize other JUNV strains but cannot Title: In silico Design of a Multivalent Vaccine Against Candida albicans", "Passage: suffering from chronic vaginal yeast infections . It consists of a truncated recombinant secreted aspartic protease 2 , currently in clinical testing by Pevion BiotechAG 10 . NDV3 targets the recombinant N-terminal region of the hyphal protein agglutinin-like sequence three protein and is being developed by NovaDigm Therapeutics 12 . Another vaccination approach from Novartis Pharmaceuticals based on monoclonal antibody targeting the heat shock protein 90 progressed through to a Phase III clinical trial but was abandoned in later stages of development due to safety concerns 13 . Finally, a prophylactic and therapeutic IgM-monoclonal antibody by LigoCyte Pharmaceuticals that targeted", "Title: Human adenovirus type 7 infection causes a more severe disease than type 3\nPassage: should also stimulate further studies of mechanisms of the different pathogenicity among human adenovirus serotypes. Title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?", "Passage: Recombinant human serotype 5 adenovirus vectors encoding GP have been evaluated in single-dose studies and have shown very acceptable safety profiles. Unfortunately, AdHu5-seropositive volunteers demonstrated statistically significantly lower GP-specific IgG titres . Increasing the administered dose of vaccine appears to overcome pre-existing immunity to this serotype; however, this is associated with increased reactogenicity . Unfounded concerns also still persist about a potential increase in HIV-1 infection rates among AdHu5-seropositive vaccinees, based on data from two Phase II studies of the Merck rAd5 HIV-1 gag/pol/nef vaccine . Use of rarer serotypes of human adenoviruses, such as Ad26 and AdHu35, can bypass Title: Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines", "Passage: Adenovirus is probably the leading viral vector platform for Ab response induction, having reached clinical trials for a variety of major diseases and attracted the interest of leading pharmaceutical companies. To represent this approach, we used human adenovirus serotype 5 expressing the model Ag OVA. AdHu5 is the most widely studied adenovirus vaccine vector, and although its use in humans is limited by the prevalence of anti-AdHu5 neutralizing Abs, it is among the most immunogenic adenovectors in mice and primates . There are a variety of differences between and within adenovirus species: as a member of adenovirus species C, AdHu5 Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: Currently, replication-deficient human adenovirus serotype 5 vaccines are being evaluated against several pathogens. Several candidates have been shown to induce protective immune responses against emerging or re-emerging infectious pathogens such as Ebola and avian influenza viruses Complete protection and long-term memory responses have also been reported in different animal models ; however, the final development of AdHu5-based vector to approved human vaccines has been hampered by the presence of natural preexisting immunity to AdHu5 which is present in a large fraction of the human population. Neutralizing antibody to porcine adenovirus 3 was not detected from pooled immune globulin representing 10", "Title: National intensive care unit bed capacity and ICU patient characteristics in a low income country\nPassage: Limitations of this study include its retrospective nature with the consequence that it could not provide the same level of evidence as a prospective survey. Furthermore, due to the concise format of medical records, only limited data could be retrieved for this audit. For example, information on whether patients received mechanical ventilation; the volume of fluids; and drugs was not available. According to anecdotal evidence, 99% of all admissions are mechanically ventilated; however, the lack of data to support this precludes us stating this as a fact. Other ICU-relevant data would have allowed better description of the study population. More Title: Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review", "Passage: The lack of inclusion of relevant factors in the methods was the most common limitation acknowledged by the authors. These included: spatial and socio-economic heterogeneity, seasonality, changing immunity, and other environmental drivers. In almost 20% of papers, the authors identified reporting bias as a key limitation. Examples of reporting bias were: sample collections not properly designed ; voluntary internetbased survey reflecting survey respondents' idiosyncrasies; and health-seeking behaviours and socio-economic factors affecting access to health facilities. Title: Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study", "Passage: There are several potential limitations. This was a single-centre study. Data collection was limited to variables available during usual care and resulted in an imbalance between groups. Besides, among 338 severe sepsis patients admitted to our centre during 2-year study period, most were excluded for hospital-acquired sepsis, diagnosis of tumour and receipt of chemotherapy or corticosteroid, resulting in enrolling 71 patients, which might bring enrolment bias. Another limitation of this study is that the exact time of severe sepsis onset could not be precisely determined, though we have defined the onset to be the time recordable manifestation or laboratory findings Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: A limitation to this study is that only SHCLCI cases were recorded during the study period. This unables global hospitalization burden estimates caused by seasonal influenza nor the estimation of seasonal differences in vaccine effectiveness to prevent severity and death. The system identifies the epidemiological and virological characteristics of severe forms of influenza that show changes in their virulence, but comparison between severe and non-severe cases is not feasible. The proportion of SHCLCI cases admitted to ICU and CFRs are potentially higher than other surveillance systems that monitor all hospitalised cases of confirmed influenza. This is particularly evident with regard", "Title: Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose\nPassage: the difference was statistically significant. The higher HIV-1 infection rate of HIVIGLOB-treated infants persisted throughout six months of follow-up, although differences at later time points were not statistically significant. In essence, passive immunization with HIVIGLOB did not prevent HIV-1 acquisition in any infants born to infected mothers, and may have enhanced in utero HIV-1 transmission. Title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection", "Passage: survived , with an average weight loss of 12.3% and a MTD of 6.6 \u00b1 0.6 dpi . Comparing groups with equal treatment times, there was no statistical difference between F 2 at 1 or 2 dpi . However, given that multiple administrations of F 2 were required to achieve similar protection levels demonstrated by a single injection of antisera, the results suggest that equine antisera is a superior product to F 2 in terms of efficacy, possibly due to a longer in vivo half-life of equine antiseras. Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies", "Passage: Calibration plates for IgG1 and IgG2a assay were coated with 0.1 \u00b5g goat anti-mouse IgG . Increasing concentrations of purified mouse IgG1 or IgG2a were added to the plates. IgG1 and IgG2a responses detected from individual sample are given as concentration of H1N1-specific IgG1 and IgG2a. Title: Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated \u201cHuman Immune System\u201d Mice\nPassage: IgG response . This suggests that repeated vaccination leads to enhanced antigen-specific antibody production. The responder mice exhibited higher total IgM and total IgG concentrations in their plasma, as compared to PBS-injected and non-responder vaccinated animals .", "Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China\nPassage: 2019-nCoV patients should be admitted to singlebedded, negative pressure rooms in isolated units with intensive care and monitoring . Clinical engineering should have plans to reconstruct standard rooms . Retrofitting the rooms with externally exhausted HEPA filters may be an expedient solution. Also, the general hospital may consider procedures such as suspending elective surgeries, canceling ambulatory clinics and outpatient diagnostic procedures, transferring patients to other institutions, and restricting hospital visitors . More importantly, because the hospitals' ability to respond to the outbreak largely depends on their available ICU beds, the plan to increase ICU bed capacity needs to be determined. Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China", "Passage: > 3 weeks according to some literature and our unpublished data . Healthcare providers and those in contact with infected patients should utilize contact, droplet, and airborne precautions with N95 respirator. Strict infection prevention and control practices have been implemented and audited in our units following the infection prevention and control plan published by China's National Health Committee . In addition, wellequipped fever clinic as triage station with trained staff knowing 2019-nCoV case definitions is established. For suspected 2019-nCoV infection, several key points are crucial procedures: recording a detailed history, standardizing pneumonia workup, obtaining lower respiratory tract specimens , and Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: hospitals be needed, and social media be employed. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management", "Passage: and DR examination rooms, should be implemented properly.", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: tachypnea when admitted to the ICU, with a mean rate of 43 breaths per minute . Arterial blood gas analysis at ICU admission revealed profound hypoxia, with a mean PaO 2 /FiO 2 of 58.1 . White blood cell counts were low or in the normal range. All patients had elevated serum aspartate aminotransferase , lactate dehydrogenase and hydroxybutyrate dehydrogenase . At admission, all patients' levels of immunoglobulin and components C3 and C4 were in the normal range. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: tachypnea when admitted to the ICU, with a mean rate of 43 breaths per minute . Arterial blood gas analysis at ICU admission revealed profound hypoxia, with a mean PaO 2 /FiO 2 of 58.1 . White blood cell counts were low or in the normal range. All patients had elevated serum aspartate aminotransferase , lactate dehydrogenase and hydroxybutyrate dehydrogenase . At admission, all patients' levels of immunoglobulin and components C3 and C4 were in the normal range. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 \u00d7 10 copies in three patients and was Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: 1 \u00d7 10 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The", "Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Home caregivers 1 Clean and disinfect hands after contact with the patient, before leaving patient's room or the house, before and after eating, after using the toilet and after entering house from outside . Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Throughout the period of home care, healthcare personnel should perform regular follow-up through face-to-face visits or phone interviews to follow the progress of symptoms and, if necessary, specific diagnostic tests should be conducted . Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Persons with close contacts and suspicious exposure should be advised to have a 14-day health observation period, which starts from the last day of contact with the 2019-nCoV infected patients or suspicious environmental exposure. Once they display any symptoms, especially fever, respiratory symptoms such as coughing, shortness of breath, or diarrhea, they should reach out for medical attention immediately . Contact surveillance should be carried out for those who had exposed to accidental contact, low-level exposure to suspected or confirmed patients, i.e. checking any potential symptoms when carrying out daily activities . See Table 3 for details . Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: If they had travelled to Hubei Province in the past 14 days and is in fever, cough or difficulty in breathing, they should: see a doctor immediately; call the doctor about his/her recent trips and symptoms before going to the doctor's office or emergency room; avoid contact with others; not to travel around; cover mouth and nose with a tissue or sleeve when coughing or sneezing; and wash hands with soap and water for at least 20 s. If soap and water are not available, use alcohol-based hand sanitizers .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: surface , and the term \"phage-displayed library\" to refer to a diverse pool of recombinant filamentous phage displaying an array of polypeptide variants . Such libraries are typically screened by iterative cycles of panning against an immobilized protein of interest followed by amplification of the bound phage in E. coli cells. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: surface , and the term \"phage-displayed library\" to refer to a diverse pool of recombinant filamentous phage displaying an array of polypeptide variants . Such libraries are typically screened by iterative cycles of panning against an immobilized protein of interest followed by amplification of the bound phage in E. coli cells. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date.", "Title: Transcriptional regulation of secretory capacity by bZip transcription factors\nPassage: pathway commonly known as the unfolded protein response . The UPR alleviates ER stress by increasing transcription of the chaperone proteins and lipids that increase folding capacity in the ER, as well as upregulating other components of the secretory machinery. The UPR also decreases protein load by increasing production of the ERAD machinery that degrades misfolded proteins . Finally, the UPR reduces protein load through the attenuation of protein translation . If ER homeostasis is not restored, the UPR then triggers the execution of cytotoxic programs leading to cell death. Title: Regulated Ire1-dependent decay of messenger RNAs in mammalian cells", "Passage: load of new proteins through transcriptional induction of secretory pathway components and general translational attenuation. One of the key players in the UPR is Ire1 , a conserved transmembrane protein with a luminal domain that senses protein misfolding in the ER. Title: Transcriptional regulation of secretory capacity by bZip transcription factors\nPassage: UPR alleviates ER stress by increasing transcription of the chaperone proteins and lipids that increase folding capacity in the ER, as well as upregulating other components of the secretory machinery. The UPR also decreases protein load by increasing production of the ERAD machinery that degrades misfolded proteins . Finally, the UPR reduces protein load through the attenuation of protein translation . If ER homeostasis is not restored, the UPR then triggers the execution of cytotoxic programs leading to cell death. Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: The UPR pathways trigger a complex network of signals via three ER transmembrane stress sensors: inositol-requiring enzyme 1 a/b , PKR-like ER kinase and activating transcription factor 6 , depicted schematically in Figure 1 . Under homeostatic condition, the ER luminal domains of these sensor proteins are inactive, due to association with glucose regulating protein 78 . GRP78 has a high affinity for misfolded and unfolded proteins: when luminal load of misfolded protein increases, GRP78 is released from the ER stress sensors, which are then free to initiate downstream signalling outside the ER.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In humans, overt disease was given the name Middle East respiratory syndrome, with the acronym MERS. From intermittent animal-to-human spill-over events, the MERS-CoV spreads sporadically among people, causing more severe disease among older adults, especially males, with pre-existing diseases. The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown", "Title: Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses", "Passage: The cardiac glycoside ouabain is an inhibitor of ATP1A1 that has been used to treat congestive heart failure in European countries . The PHB inhibitor rocaglamide is a flavagline from an Aglaia tree used in traditional Chinese medicine that has potent anticancer activity . To examine whether pharmacological inhibition of ATP1A1 or PHB inhibited LCMV multiplication, we pretreated human , nonhuman primate , and rodent cells with ouabain or rocaglamide and infected them with rLCMV/eGFP . Ouabain treatment resulted in a strong dosedependent inhibition of eGFP expression in infected human-and nonhuman primate cells, but did not affect eGFP expression intensity Title: Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus", "Passage: secondary matrix protein VP24-apart from its role in the evasion of host immune response, nucleocapsid formation, and regulation of replication-has an important role in viral budding and egress. Na + /K + -ATPase ATP1A1 is detected to have a close interaction with VP24 of EBOV during replication. Ouabain, at a non-cytotoxic concentration of 20nM, is able to suppress the replication of the EBOV in human MRC-5 cells . Among the three cardiac glycosides that may include digoxin, digitoxin, and ouabain, only digoxin is commonly used in clinical practice. Ouabain, because of its poor oral availability, is used primarily as a Title: Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses", "Passage: anti-LCMV activity of ouabain . Nevertheless, ATP1A1-mediated Src signaling could plausibly contribute to the inhibitory effect of ouabain on JUNV multiplication as similarly to that observed with MHV. Moreover, cell entry of JUNV occurs also by clathrin-mediated endocytosis , a process affected by Src signaling. Ouabain has been clinically used in several European countries for the management of congestive heart failure, whereas bufalin has been tested in clinical trials for cancer treatments , and the CST digoxin has been FDA-approved since 1997 to treat heart failure and atrial fibrillation. Hence, opportunities for the repurposing CSTs have potential as therapeutics to Title: Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses", "Passage: fresh cell monolayer and identified infected cells based on ZsGreen expression. To assess the effect of ouabain on de novo assembly of infectious progeny we determined normalized ratios of ZsGreen + cells . The second experiment involved infection of cells with WT LCMV, and 48 h later we washed infected cells three times to remove the extracellular infectious progeny produced during the first 48 h of infection. Then, fresh media containing ouabain or DMSO vehicle control were added, and 24 h later we determined virus titers in TCS . Results from both experiments consistently showed that ouabain did not inhibit", "Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: RTIs are a major cause of morbidity and mortality worldwide. Acute RTI is most common in children under five years of age, and represents 30-50% of the paediatric medical admissions, as well as 20-40% of hospitalizations in children. Respiratory infections cluster during winter and early spring months. The leading viral agents include respiratory syncytial virus , influenza A and B viruses, parainfluenza viruses , and human adenoviruses . In addition, there is a continuously increasing list of new respiratory viruses that contribute significantly to the burden of acute respiratory infections, such as the recently identified human metapneumovirus and human Bocavirus Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus", "Passage: Text: Viral Respiratory tract infections represent a major public health problem because of their world-wide occurrence, ease of transmission and considerable morbidity and mortality effecting people of all ages. Children are on average infected two to three times more frequently than adults, with acute RTIs being the most common infection in childhood . Illnesses caused by respiratory viruses include, among others, common colds, pharyngitis, croup, bronchiolitis, viral pneumonia and otitis media. Rapid diagnosis is important not only for timely therapeutic intervention but also for the identification of a beginning influenza epidemic and the avoidance of unnecessary antibiotic treatment . Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus", "Passage: The most common viruses detected were RSV and rhinovirus accounting for almost 60% of all cases. Both viruses were reported previously by others as the major aetiology for respiratory viral infections in young children with rhinoviruses being recognized increasingly for their role in lower respiratory tract infections . Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: Acute RTIs are classified as upper and lower RTI , according to the involved anatomic localization. URTIs cause non-severe but widespread epidemics that are responsible for continuous circulation of pathogens in the community. LRTIs have been classified as frank pneumonia and bronchiolitis with clinical, radiological and etiological features that usually overlap . Viruses are again the foremost agents of LRTIs often misdiagnosed as bacterial in origin and hence treated with antibiotics unnecessarily .", "Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China\nPassage: The survey revealed that over half of the TB patients were 65 years and older in Shandong, while the over 65's were more likely to present with abnormal CXRAY and persistent cough. Similar trends have been documented in other developed cities such as Hong Kong and Singapore . These high rates may reflect the higher TB rates in the past and decline in immunity in the over 65's. How to treat elders with TB and other complications such as diabetes remains an ongoing challenge in China and similar settings. Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: from people 65 years or older. The ratio between over 65's and 15 to 64 years old was 8.4 in sputum positive cases and 5.9 in bacteriologically confirmed cases. The ratio between rural and urban areas was 2.7 in sputum positive cases and 4.8 in bacteriologically confirmed cases. Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China\nPassage: the yields were higher in over 65's compared with the general Table 2 Prevalence rates of sputum positive TB cases, bacteriologically confirmed TB cases and all cases in Shandong, China, 2010 No population. Although using CXRAY to examine everyone is not feasible, it can be used in routine elder physical examinations. The China public health package now covers free CXRAY for elders, as well annual employee body examinations provided free CXRAY. Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: The crude prevalence rate in Shandong in 2010 of sputum positive cases was 22.1 , bacteriologically confirmed cases was 36.8 , and all cases were 337.1 per 100,000 in adult population . The adjusted prevalence rates of the whole population in Shandong were17.8 , 27.8 and 239.4 per 100,000 in 2010. A remarkable decline of 82.0%, 80.2% and 31.4% was observed in TB prevalence rates of sputum positive, bacteriologically confirmed, and all cases, respectively, compared to the adjusted rates in 2000 . Large declines were observed in males between 40 and 65 years old, and in females over 60 years", "Title: Temporal trends in the discovery of human viruses\nPassage: We confirmed that our model reproduced the observed slight downward trend in the rate of discovery since 1954 and the observed variance in the data from 1954 to 2006 . The distribution of the number of virus species discovered per year shows slight overdispersion which falls within the predicted range . Together, these results support our choice of model, even though we do not explicitly consider heterogeneity in the probability of discovering a given species in any one year or temporal variation in sampling effort, detection techniques and reporting. Title: Temporal trends in the discovery of human viruses\nPassage: yield useful estimates of the additional parameters required. Title: Temporal trends in the discovery of human viruses", "Passage: We used piecewise linear regression to test for changes in the slope of the discovery curve. The results suggested upswings in 1930 and 1954 (1953 -1956 . We therefore restricted detailed analysis to the period 1954-2006. Title: Temporal trends in the discovery of human viruses\nPassage: is therefore of considerable interest.", "Title: Studying copy number variations using a nanofluidic platform\nPassage: A real-time PCR reaction was also performed on these 48 samples. Twenty-four replicates were used for each sample. Although the average copy numbers were close to the digital array data, large fluctuations were observed in the 24 reactions of each sample. Studies on other genes showed that real-time PCR does not always produce accurate results . Title: Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens", "Passage: In addition, the intra and inter-assay reproducibility of quantification for all primer sets was evaluated using three replicates of each standard dilution in each of three real-time PCR assay runs. The coefficient of variation for the C values was #3.3% and #6.7% for intra-and inter-assay, respectively. All the data depicting mean C , standard deviation , and CV for each primer set selected for the real-time PCR array with each standard concentration are shown in Table S2 . Title: Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens", "Passage: The developed analytical standards were used to calculate the intra and inter-assay reproducibility of quantification for each virus-specific primer set. Mean C values, standard deviation and coefficient of variation were calculated from the data obtained in three replicates of each standard dilution for the intraassay reproducibility, and in three real-time PCR assays consisted of three replicates each for the inter-assay reproducibility. CV was calculated as SD/Mean C * 100%. Title: A cost effective real-time PCR for the detection of adenovirus from viral swabs", "Passage: were observed that spanned eight orders of magnitude with Cp values ranging from 14 to 40 . The intra-and inter-assay reproducibility of the real-time PCR following homogenization and heat treatment ranged from 0.03 to 4.80%, and 1.45 to 3.79%, respectively. Similarly, intra-and inter-assay reproducibility of following the nucleic acid extraction protocol ranged from 0.2 to 2.15% and 0.85 to 3.15%. As expected, the highest %CV values observed for both methods were with virus dilutions near the LoD.", "Title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA\nPassage: passages within bacteria. The complete genome sequences of rescued viruses, after extensive passages in mammalian cells showed that modifications in the E2 protein coding sequence were stably maintained. A single amino acid substitution in the RNA dependent RNA polymerase was observed in the rescued viruses vR26_E2gif and vR26, which was reversion to the parental Riems sequence. CONCLUSIONS: These results show that targeted recombination-mediated mutagenesis provides a powerful tool for expediting the construction of novel RNA genomes and should be applicable to the manipulation of other RNA viruses. Title: Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization", "Passage: of ZIKV strain FSS13025 was used to amplify the DNA template for in vitro transcription of ZIKV 5 0 end RNA. JEV UFS mutants were generated by site-directed mutagenesis, the resultant plasmids were utilized to amplify the DNA templates for in vitro transcription of the corresponding JEV 5 0 RNA mutants. Title: Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization\nPassage: Site-directed mutagenesis method was employed for the generation of ZIKV fragments containing the desired UFS mutations, the generated Not I-Avr II restriction fragments were then subcloned into the infectious clone of ZIKV strain FSS13025 , which was kindly provided by Professor Pei-Yong Shi. Title: Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles", "Passage: For example, RdRp mutator variants of chikungunya virus and Sindbis virus are attenuated in fruit flies and mice . The attenuation observed in vivo has been directly correlated with the increased mutation rates that would presumably result in higher frequencies of lethal mutations. Indeed, mutator strains of RNA viruses present mutation frequency profiles similar to those of wild-type-like viruses whose mutation rates are extrinsically increased by treatment with RNA mutagens in studies evaluating lethal mutagenesis as an antiviral strategy . However, while many determinants that alter RdRp fidelity have been identified, the enzymatic mechanisms or dynamics by which this occurs", "Title: Globalization and emerging governance modalities\nPassage: becomes impossible. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: and a higher standard across the board. Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust", "Passage: Achieving these changes would require the institutions that demand internationally comparable data from international organisationsmostly UN member states and their development organisations but also private foundations and multilateral health fundsto recognise that socially robust processes may result in slightly lower frequency and even somewhat less standardised measures, even as they lead to more use of data to guide service provision locally and nationally. We note that many richer nations do not themselves report health data in the formats required of most lowand middle-income nations, so they should have little difficulty understanding the utility of local variation. Title: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management", "Passage: The above improvements in the healthcare sector can only be achieved if different smart city products are fashioned to support standardized protocols that would allow for seamless communication between themselves. Weber and Podnar \u017darko suggest that IoT devices in use should support open protocols, and at the same time, the device provider should ensure that those fashioned uphold data integrity and safety during communication and transmission. Unfortunately, this has not been the case and, as Vermesan and Friess explain, most smart city products use proprietary solutions that are only understood by the service providers. This situation often creates unnecessary fragmentation", "Title: Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection\nPassage: function before and post infection of H7N9. In particular, this group of patients had pre-existing conditions, which may also have affected the HRQoL results. Patients who had suffered acute pathologies reported significant decreases in quality of life, whereas other patients with pre-existing conditions reported significant improvements in terms of reduced BP and improved MH, VT and SF scores 21 . In our study, H7N9 survivors had significantly higher VT and MH scores than the population norms. Thus, those scores may have been higher at baseline, i.e., prior to admission. Finally, after discharge from the hospital, there was no significant improvement; Title: Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection", "Passage: however, whether improvements in physical and mental health would have been detected had the follow-up duration been longer is unknown. Thus, further expanded research is needed. Title: Fast-track surgery improves postoperative clinical recovery and cellular and humoral immunity after esophagectomy for esophageal cancer\nPassage: All analyses were performed with the statistical package SPSS . A P value of <0.05 was considered significant. Title: Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection", "Passage: To test whether EAP could protect H5N1 infected mice, mice were treated with EAP at a dose of 5, 10, 25, or 50 mg/kg body weight intranasally once daily for 5 days prior to viral challenge with 120 PFU. Ten mice per group were monitored for 14 days for the survival rate. As shown in Figure 2 , all mice receiving PBS died at day 11. Mice administrated 25 mg/kg EAP had a survival rate of 50% at day 14, which was significantly higher than those receiving PBS . EAP treatment of 10 mg/kg and 50 mg/kg also appeared to", "Title: Haunted with and hunting for viruses\nPassage: Tan and colleagues specifically focused on the newly-emerged MERS-CoV. The virus was identified in 2012 in the Middle East with some exported cases to Europe. In 2013 the virus has been re-emerging and expanding its borders to more European countries. In the initial diagnosis, the pan-coronavirus real-time reverse transcription polymerase chain reaction assay played a very important role for the identification of the causative agents. By using this method, scientists detected an expected-size PCR fragment for the corresponding conserved region of ORF1b of the replicase gene of a coronavirus. This is another example that molecular biology methods played for the Title: Insights into the Evolution and Emergence of a Novel Infectious Disease", "Passage: Zoonotic emergence of novel human infections poses a significant risk to global public health. For example, the 'Spanish flu' pandemic of 1918 probably originated in birds and caused millions of deaths worldwide . While much less virulent, the subsequent influenza pandemics of 1957, 1968 and 2009 are potent reminders of the capacity of the influenza virus to cross the species barrier into humans. Many other pathogens share this capacity: the SARS outbreak of 2003 has been linked to bats and palm civets . In 2008, a novel arenavirus which killed four out of five patients in South Africa was linked Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Text: Emerging pathogens cause new or previously unrecognized diseases, and among them, emerging zoonotic diseases are a major concern among scientists studying infectious diseases at different spatial and temporal scales . Changes in biotic and abiotic conditions may alter population disease dynamics and lead to the emergence of zoonotic infections . During the last decades, several outbreaks of emerging and re-emerging viral pathogens have occurred, affecting both purely-local and worldwide/pandemic involvement of human populations. Among the conspicuous examples are influenza A, Ebola virus, hepatitis C virus, severe adult respiratory distress , coronavirus, and human immunodeficiency virus, which challenge prevention and Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: With respect to their significance to the economy, vaccines have also been developed for many of these viruses in a bid to prevent localized infections from progressing into serious outbreaks. This has, however, proven to be a hard battle as the vaccines are unable to provide complete cross-protection among the various serotypes of each virus .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Infectious MERS-CoV added to DC, goat or cow milk and stored at 4\u00b0C could be recovered at least 72 h later and, if stored at 22\u00b0C, recovery was possible for up to 48 h . MERS-CoV titre decreased somewhat when recovered from milk at 22\u00b0C but pasteurization completely ablated MERS-CoV infectivity . In a subsequent study, MERS-CoV RNA was identified in the milk, nasal secretion and faeces of DCs from Qatar . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Camel calving season occurs in the winter months and this may be a time when there is increased risk to humans of spill-over due to new infections among na\u00efve DC populations . What role maternal camel antibody might play in delaying infection of calves remains unknown . Juvenile DCs appear to host active infection more often than adult DCs and thus the sacrificial slaughter of DCs, which must be five years of age or older , may not be accompanied by significant risk of exposure to infection. In contrast to earlier results, slaughterhouse workers who kill both younger and older Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: is an animal of ritual significance after the Hajj pilgrimage . However, MERS-CoV infection frequency is reportedly much lower than is the widespread and frequent habit of eating, drinking and preparing DC products. Daily ingestion of fresh unpasteurized DC milk is common among the desert Bedouin and many others in the KSA. DC urine is also consumed or used for supposed health benefits. Despite camel butchery being a local occupation, neither butchers nor other at-risk groups are identifiable among MERS cases; this may simply be a reporting issue rather than an unexplainable absence of MERS. A small case-control study published Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: positive DC had been infected by a variant of the same virus, harbouring the same distinct pattern of nucleotide polymorphisms. All nine DC in the owner's herd, serially sampled, reacted in a recombinant S1 antigen ELISA, with the two animals that had been RT-rtPCR positive showing a small, verifiable rise in antibody titre . A rise in titre theoretically begins 10 to 21 days after DC infection . The authors suggested that the rise in titre in DC sera which occurred alongside a declining RNA load, while the patient was actively ill and hospitalized, indicated that the DCs were infected", "Title: Incubation periods of viral gastroenteritis: a systematic review\nPassage: 1.22 . 25% of cases will become symptomatic by 4.0 days and 75% of cases will become symptomatic by 5.3 days . Because of limited data, the 5th and 95th percentiles were not estimated. Few adult volunteers exhibited symptoms when challenged with astrovirus suggesting that the virus has low pathogenicity in adults, who may be protected by antibodies acquired in childhood . As data from adult challenge studies comprised 50% of the abstractable data suitable for pooled analysis for astrovirus, our incubation period results may not be applicable to primary infections or infections in children. Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Based on 1,123 observations from ten observational studies, and five observations from one experimental study , we estimate the median incubation period for genogroup I noroviruses to be 1.1 days with a dispersion of 1.82 . 5% of genogroup I norovirus cases will become symptomatic 0.4 days after infection and 95% of cases will develop symptoms by 3.0 days . Title: Incubation periods of viral gastroenteritis: a systematic review\nPassage: Based on 106 observations from four observational studies , we estimate the median incubation period for sapoviruses to be 1.7 days with a dispersion of 1.48 . Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: We found 20 estimates of incubation period for astrovirus, including five original estimates, seven estimates with sources, and eight estimates where the original source was not provided . Statements of incubation period were generally between 1 and 5 days . Three original studies containing data suitable for pooled analysis were found: two experimental challenge studies in adult volunteers and an observational study describing a series of outbreaks in a child care center in Houston, Texas, USA . From these three studies we estimate the median incubation period of gastroenteritis due to astrovirus to be 4.5 days with a dispersion of", "Title: Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA\nPassage: al. 17 and Furuse et al. 26 Since M1 protein plays an important role in virus assembly and budding, any change in M1 can have deleterious effect on virus survival, whereas M2 protein is integral membrane protein forming pH-gated channels in the viral lipid membrane. 23 More sites in the M2 protein under positive selection are located in the extracellular domain, which is recognized by the host immune response system. Thus, to evade host immune response, M2 protein is more susceptible to mutations. 26, 39, 40 Also, higher rate of amino acid variations in M1 and M2 proteins was observed Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Matrix protein 2 is highly conserved among influenza A virus strains, indicating that M2 is an attractive target for developing a universal vaccine . In previous studies, various constructs of the M2 vaccine have been developed and tested, including recombinant Escherichia coli expressing M2 fusion protein, adenoviral vectors expressing the M2 protein, plasmid DNA encoding M2 and peptides encoding M2e , each of which was able to elicit protective immune responses in mice. However, the drawback of these M2-based vaccines is their low immunogenicity; additionally, most of them would require intramuscular injections. Therefore, many strategies have been applied focusing on Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Matrix protein 2 is highly conserved among influenza A virus strains, indicating that M2 is an attractive target for developing a universal vaccine . In previous studies, various constructs of the M2 vaccine have been developed and tested, including recombinant Escherichia coli expressing M2 fusion protein, adenoviral vectors expressing the M2 protein, plasmid DNA encoding M2 and peptides encoding M2e , each of which was able to elicit protective immune responses in mice. However, the drawback of these M2-based vaccines is their low immunogenicity; additionally, most of them would require intramuscular injections. Therefore, many strategies have been applied focusing on Title: Protection against homo and hetero-subtypic in\ufb02uenza A virus by optimized M2e DNA vaccine", "Passage: Influenza virus M2 protein is an integral membrane protein expressed on the viral surface in low quantities, while being abundantly present on the surface of infected cells . This expression pattern plays an important role in viral replication. The M2 protein consists of an N-terminal extracellular region , transmembrane region, and C-terminal cytoplasmic tail region. The M2e is composed of 24 amino acids and is highly conserved among different influenza A subtypes . Thus, this region may be a good candidate epitope for the preparation of a universal vaccine. However, in its natural state, viral M2e has low immunogenicity and", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: There are eleven studies that focus on SARS-CoV diagnostic testing . These papers described diagnostic methods to detect the virus with the majority of them using molecular testing for diagnosis. Comparison between the molecular test and serological test showed that the molecular test has better sensitivity and specificity. Hence, enhancements to the current molecular test were conducted to improve the diagnosis. Studies looked at using nested PCR to include a pre-amplification step or incorporating N gene as an additional sensitive molecular marker to improve on the sensitivity . Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Serological testing such as ELISA, IIFT and neutralization tests are effective in determining the extent of infection, including estimating asymptomatic and attack rate. Compared to the detection of viral genome through molecular methods, serological testing detects antibodies and antigens. There would be a lag period as antibodies specifically targeting the virus would normally appear between 14 and 28 days after the illness onset . Furthermore, studies suggest that low antibody titers in the second week or delayed antibody production could be associated with mortality with a high viral load. Hence, serological diagnoses are likely used when nucleic amplification tests are Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The first validated diagnostic test was designed in Germany. Corman et al. had initially designed a candidate diagnostic RT-PCR assay based on the SARS or SARS-related coronavirus as it was suggested that circulating virus was SARS-like. Upon the release of the sequence, assays were selected based on the match against 2019-nCoV upon inspection of the sequence alignment. Two assays were used for the RNA dependent RNA polymerase gene and E gene where E gene assay acts as the first-line screening tool and RdRp gene assay as the confirmatory testing. All assays were highly sensitive and specific in that they did Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: There is no perfect test for the diagnosis of infl uenza. Virus culture, the present 'gold-standard test' is not 100% sensitive and does not provide results in a time-frame that allows optimal use of potentially effective antiviral treatment. Although rapid diagnostic tests provide results in less than 30 minutes, they are signifi cantly less sensitive and do not differentiate between different subtypes of infl uenza A virus. Rapid testing is only offered after the fi rst culture-confi rmed cases of infl uenza are reported from the community. Molecular assays; reverse transcriptase polymerase chain reaction and real-time RT-PCR targeting conserved regions", "Title: Reverse Genetics Approaches for the Development of Influenza Vaccines\nPassage: Adjuvants have been shown to enhance the immune response elicited by an antigen and could be used to improve the immunogenicity of IIV . The use of adjuvants could also reduce vaccine dose, stretching antigen and vaccine supplies. Currently, FDA-licensed adjuvants for influenza vaccine usage include aluminum salt and the squalene oil-in-water emulsion systems MF59 ) and AS03 . However, most of the current IIVs do not contain any type of adjuvant, but many are under investigation. Title: Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus", "Passage: , and monophosphoryl lipid A have achieved widespread human use. Most adjuvants either activate pattern recognition receptors ) in the innate immune system or improve the delivery of antigens to the immune system. The most common adjuvant, alum, comprised of aluminum salts, has been used in humans since 1932, is approved for human use by the FDA, and is a component of numerous licensed vaccines such as Diphtheria, Tetanus and Pertussis vaccines, and hepatitis B vaccines. MPLA with Alum is used for the hepatitis B vaccine, Fendrix, and the human papillomavirus vaccine, Cervarix, and has extensive human safety data in Title: Safety, Reactogenicity, and Immunogenicity of Inactivated Monovalent Influenza A(H5N1) Virus Vaccine Administered With or Without AS03 Adjuvant", "Passage: In summary, we demonstrated the feasibility of a strategy in which proprietary adjuvants available in the US National Prepandemic Influenza Vaccine Stockpile could be combined with pandemic avian antigens produced by other manufacturers . This approach has the potential to substantially increase the supply of effective vaccine and to add flexibility and speed to the responses available for controlling an emerging influenza pandemic. Title: Oil-in-water emulsion adjuvants for pediatric influenza vaccines: a systematic review and meta-analysis", "Passage: stimulates the local inflammatory response at the injection site and thus increases the uptake of antigen by activated dendritic cells 43 . Similarly, AS03 facilities a stronger antibody response by inducing a local cytokine and chemokine response at the injection site to enhance antigen uptake 43 . Studies in young children also showed that MF59-adjuvanted influenza vaccines produced a stronger and more homogeneous innate transcription response like that of adults, thus resulting in significantly higher HI titers than those elicited by non-adjuvanted vaccines 22 .", "Title: Markers of exacerbation severity in chronic obstructive pulmonary disease\nPassage: We were also aware that the clinical studies we analysed differed with respect to which comorbidities or identifiable causes for exacerbations were reported. Most patients were elderly and therefore were more likely to be suffering from one or more co-existing diseases such as asthma or cardiovascular disease. Such co-morbidity makes interpretation of our findings more difficult with respect to the true causes of exacerbations. If their aetiology could be determined, then susceptible patients such as those in Level I could be identified and new treatments developed to help prevent their onset and related hospital costs. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Finally, the compatibility between the studies of COPD exacerbation that we analysed may have been limited by substantial variations in the time and location of studies. Exacerbations are more likely in summer but many studies failed to report the time of year or the time period for study implementation. Thus, seasonal effects, combined with the low incidence of exacerbations per patient, could represent an inherent bias. In addition, different institutions probably had different standards with respect to diagnosis and management of COPD exacerbations when these studies were performed. Such variations may also explain any observed inconsistencies in our findings. However, Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Lastly, our findings were obtained from COPD patients that had experienced at least one exacerbation during the study assessment period. In the same studies, there were also patients who did not experience an exacerbation. This indicates that a fraction of COPD patients may be regarded as being susceptible to an exacerbation whereas another fraction is 'exacerbation-free'. It would be interesting to determine how the variables we identified in our study change in the latter patient group according to FEV 1 . Some published studies have stratified COPD patients on the basis of exacerbation frequency; this is generally done by categorising", "Title: Advances in Directly Amplifying Nucleic Acids from Complex Samples\nPassage: Saliva and sputum are abundant and easy to obtain, and are thus attractive samples for diagnostics. Saliva flows into the oral cavities through salivary glands, where blood vessels secrete the same protein and nucleic acid biomarkers as in peripheral blood. In contrast with blood-based samples, saliva sampling does not require trained technicians, presents fewer antigen-associated risks, and can be more easily purified . Sputum, a necessary sample for respiratory infections, is mucus from the lower airways. Unfortunately, saliva and sputum are very heterogeneous with respect to the distribution of organisms, chemical composition, and the presence of outside contaminants such as Title: Selection of key recommendations for quality indicators describing good quality outbreak response", "Passage: Two researchers performed the extraction of recommendations independently on a sample consisting of 25% of all selected sources . The researchers extracted good quality response recommendations from the selected literature. Discrepancies between the two researchers were discussed until consensus was reached. After reaching consensus on this 25% sample, one researcher continued to extract recommendations from the remaining selected literature . The two researchers examined the total set of recommendations to remove identical recommendations. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms. LRT samples are also best for attempting isolation of infectious virus, although the success of culture is reduced when disease persists . Recommended sample types include bronchoalveolar lavage , tracheal/tracheobronchial aspirate, pleural fluid and sputum . Fresh samples yield better diagnostic results than refrigerated material and if delays in testing of \u226572 h are likely, samples should be frozen at \u221270\u00b0C . If available, lung biopsy or autopsy tissues can also be tested . Title: Near-Patient Sampling to Assist Infection Control\u2014A Case Report and Discussion", "Passage: The other related, practical issue is then to define what the clinically relevant threshold should be for the limit of detection of any molecular assay used to test such air samples. The following example illustrates some of these issues. Note that the figures discussed are for illustrative purposes only but the methods and equipment are based on some of the authors' current experiments.", "Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: ranged from 36%-60% overall, which is alarmingly high compared with all previous outbreaks of human cases of seasonal influenza in the United States, for which the CFR has ranged from 0.04%-1.0% . This high level of illness severity and high mortality rate was unexpected and increased disease burden, resulting in concern among clinicians and public health officials; however, the risk factors that are most highly associated with the deaths from avian influenza were not clear. Title: Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People\u2019s Republic of China", "Passage: of cases were men and the median age was 61 years . Forty-four died resulting in a case fatality proportion of 33% . Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: For the H7N9 group, the median number of days from onset to confirmation of infection in the fatality groups was slightly longer than that of survivors vs. 8 days, p = 0.011]; however, the median number of days from onset to outcome vs. 31 days, p < 0.001] and number of hospitalization days vs. 25 days, p < 0.001] in the fatality groups was slightly less than those relating to survivors, respectively . Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses", "Passage: The ratio of comorbidity was much higher in the H5N1 and H7N9 virus fatalities than in the survivors vs. 8.33% , p = 0.046 for H5N1; 58.6% vs. 34.8% , p < 0.001 for H7N9]. Only two H5N6 survivors were found to have underlying conditions, one of which was pregnancy, while only 22.2% of the H9N2 survivors had comorbidities. In total, the rate of comorbidities in the H7N9 fatality and survivor groups was slightly higher than that of the H5N1 groups .", "Title: Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database\nPassage: away from hospitals . The subjects for this investigation were randomly selected and unfiltered. The time period of each group was consistent and was evenly distributed in two weeks. We made further inquiries 189 amicable interviewees who were willing to take the SMP tests about their background, as well as the privacy protection in SMP data. The patients were fully informed before the voluntary agreements for SMP tests were signed. The researchers obtained the respective remaining samples from nurses after the ordinary blood tests were performed. No extra sampling of blood was performed in this study. Title: Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database", "Passage: room for blood sampling. Our researchers were permitted to wait in the room and give the patients suggestions to permit the additional SMP tests accompanied by their original blood tests. The data acquisition was performed in a passive way, i.e., the participators were randomly involved in. We orally interviewed the patients, doctors and nurses regarding their attitude towards the SMP test. The investigators for survey studies were divided into two groups: one group interviewed the people who will get their blood tested in the blood-collection room of hospitals, whereas the other group randomly interviewed the pedestrians in city streets far Title: A simple novel device for air sampling by electrokinetic capture", "Passage: Authors' contributions JG contributed to experimental design, performed the air sampling and mold spore data reduction, and had primary responsibility for drafting the manuscript. PG contributed to the experimental design and reviewing of the manuscript. GS performed the atomic force microscopy and interpretation of the results therefrom. AF performed the PCR and amplicon analysis and wrote that part of the methods section. JH-M was responsible for the PCR and amplicon analysis experimental design and data reduction and contributed to the manuscript writing. JAG contributed to the experimental design and manuscript review and writing. All authors read and approved the final Title: Near-Patient Sampling to Assist Infection Control\u2014A Case Report and Discussion\nPassage: After discussion with our local institutional review board it was agreed that this air sampling constituted environmental sampling and therefore did not require a formal ethics approval.", "Title: Treatment of Neuroterrorism\nPassage: Venezuelan equine encephalitis virus is an alphavirus that is most commonly found in Central and South America. It is transmitted to humans by mosquitoes. In case of a bioterrorist attack, the distribution would be made through aerosols . The virus usually leads to an initial severe febrile illness in nearly everyone exposed at 1 to 6 days after exposure. Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas\nPassage: within the VEE subtype, subtype II Everglades virus , which is found only in Florida, can cause neurologic disease in humans and equids . Subtype IIIA, Mucambo virus, also causes febrile disease in humans . Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas", "Passage: hundreds-of-thousands of cases over a period of months to a few years. Prior to the 1980s, VEE epizootics involving high case-fatality rates were frequently recorded. Because horses have been an important component of the local agricultural economies within many Latin American regions, VEE has often had a sizeable economic impact as well as a direct effect on public and veterinary health . Recent outbreaks during the 1990s in Venezuela, Colombia and Mexico have demonstrated the potential for VEEV to re-emerge periodically from enzootic progenitors . The emergence of VEEV into an epidemic/ epizootic form has been associated with specific mutations Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas", "Passage: climate change, which also increases the potential for other VEEV subtypes to spread northwards and establish enzootic transmission cycles. Although many VEE complex viruses have not been implicated in human disease, those that are associated with human disease can cause acute, often severe febrile illness that may progress to encephalitis, causing severe human morbidity and mortality . Patients who survive encephalitis are often left with permanent neurologic sequelae, and the cost for treatment and long-term care related to a single case can be several million dollars . In addition to VEEV , which cases the majority of the encephalitis cases", "Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Email address Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: Arabia, Sweden, Turkey, Poland, and the United States. Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: lay press sources. Of note, errors in newspaper writings were associated with anonymous authorship and being a letter to the editor or editorial. Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: of this manuscript.", "Title: Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities\nPassage: The results of stratification analysis by anomalies are shown in Additional file 1: Table S2 . The estimates were similar to those for the periods defined by absolute values of meteorological factors, in terms of magnitude and changing patterns. But the likelihood ratio tests showed more significant interaction for temperature or vapor pressure, and less for relative humidity. Title: Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities", "Passage: There are several limitations in our study. Firstly, our study is based on 3 years of surveillance data which may not have enough power to allow assessment of exposureresponse curves for the effects of environmental factors. Nevertheless, our findings did suggest an increasing trend of influenza associated mortality risks across the periods of low, middle and high vapor pressure, although such findings may be applicable only to the warm climates. Secondly, we only investigated the effect modification of environmental factors through a simple interaction model, but there were other unadjusted factors, including host susceptibility and virulence of influenza strains. These Title: Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities", "Passage: guinea pig experiments showed dramatically reduced transmission rates . In future, we may examine the seasonal variation in influenza effects in other cities to assess whether such a seasonal variation, if common in subtropical and tropical cities, is consistently determined by environmental factors, or by other factors such as host immunity and virus virulence. The results for the different age groups suggested that the modification effects of environmental factors may mainly lie in the elderly aged over 65 years, as the consistent increasing trend over the low to high vapor pressure periods was only observed in this age group. However, Title: Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities", "Passage: factors are unlikely to work independently with environmental factors. Other environmental factors such as ultraviolet radiation , rainfall have been proposed to play a role in the regulation of influenza seasonality, although evidence is rather limited compared with the three factors we chose to investigate . Lastly, we did not adjust for the vaccination rate in our model. In 2003, vaccination rate was 191 doses per 1,000 total population in Hong Kong , slightly higher than the rate of 129 doses/1,000 total population in Guangzhou . However, it is not clear when people received vaccination; therefore we were unable to", "Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain\nPassage: The 1918-1920 influenza pandemic, or the so-called Spanish flu, was responsible for more than 50 million deaths worldwide . In Europe, the excess mortality rate associated with the 1918-1919 influenza pandemic has been estimated at 1.1%, or approximately an 86% increase in all-cause mortality . This pandemic rapidly spread in a series of pandemic waves that gripped the world beginning in early 1918 . However, according to results of various phylogenetic and molecularclock analyses, the initial circulation of the virus from avian or swine and other mammal species to humans may have occurred a few years earlier . Moreover, the Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: It is postulated that 10% of the worldwide population is infected by an influenza virus each year, resulting in a total economic burden of $87.1 billion USD . As a testament to the significant toll posed by influenza on public health and healthcare systems, the US Centers for Disease Control and Prevention estimated that from 2010 to 2015, influenza infections resulted in 9.23-35.6 million illnesses and 139,000-707,000 hospitalizations annually in the US alone . It has been suggested that children are likely the primary transmitters of influenza . Lethal influenza infections are primarily associated with high risk populations, including infants Title: 1918 Influenza: the Mother of All Pandemics\nPassage: z50 million and were arguably as high as 100 mil- Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: The name Spanish flu comes from the first news reports of influenza-like-illness in Madrid in the late spring of 1918. However, this pandemic gained its nickname because the first mentions of the virus were published in Spain, where the press faced no censorship during World War I, owing to the country's neutrality . Many people fell ill with respiratory symptoms in May 1918, including King Alfonso XIII, which was well documented in the press . Because respiratory disease outbreaks occurred in neighboring France as early as April 1918, it is likely that the virus was introduced into Spain via Spanish", "Title: Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda\nPassage: The laboratory capacity for the isolation and identification of bacterial pathogens has been established at the NRL. Specimens for bacteria such as Vibrio cholerae, Salmonella typhi, Shigella species, Neisseria meningitidis and Haemophilus influenzae are collected from the peripheral levels and transported to the NRL where they are analyzed. The results are fed back to the districts and also shared with WHO/AFRO on a monthly basis. Decentralization of services was also implicated in expansion of access to antiretroviral treatment at the national level. Following the Rwanda National Paediatric Conference in 2004, there was recognition that early infant diagnosis of mother-to-child transmission Title: Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda", "Passage: in turn ships these specimens to the Ugandan Virus Research Institute in Entebbe, Uganda for confirmation and characterization of the organism. The results are reported back to Rwanda's NRL and EPI offices and then shared with the WHO. The results are communicated to the district health team and health facilities that use the results to inform timely and relevant public health response actions. Title: Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda", "Passage: For monitoring of the measles program, serum specimens from patients with suspected measles are collected and transported from the health facilities to the NRL. The samples are analyzed for viral antibodies by ELISA. The results are given to EPI for their use in determining a timely response. The results are shared with WHO-AFRO on a monthly basis. Serum specimens also are sent to UVRI on a quarterly basis for external quality control. In addition, the NRL receives quality control panels every quarter from UVRI. Title: Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa", "Passage: On 45 hectares, the CIRMF campus has a working space of 2,500 square meters composed of a main building, laboratories, service buildings, and living accommodations . The present high containment and high security laboratory, operated by the Emerging Viral Diseases Unit , is one of 2 laboratories in Africa that can manipulate Risk Group 3/4 Agents . Research, including isolation and characterization of these highly pathogenic viruses is performed in accordance with international rules defined by WHO on the handling Risk Group 3/4 Agents Updated equipment includes a double door autoclave, thermo regulated cabinet, a high security centrifuge system, a", "Title: Risk factors for severe acute lower respiratory infections in children \u2013 a systematic review and meta-analysis\nPassage: Hospitalization for acute lower respiratory infections in young children poses a substantial burden on health services, especially in developing countries. In spite of this, the evidence regarding the risk factors for this major burden of disease is in many cases sparse, of variable quality, and not generalizable. However, since the majority of these risk factors are potentially preventable, governments should consider what action can be taken to decrease the prevalence of these risk factors. This, along with increasing coverage of vaccines for Streptococcus pneumoniae and Haemophilus influenzae type B, should substantially decrease the burden of childhood pneumonia in developing countries. Title: Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology", "Passage: South Africa is a middle-income country, but there is great variation in socioeconomic status with some provinces that are more similar to low-income countries . This results in some populations within the country having a disproportionately higher level of exposure to risk factors for communicable disease. These include environmental risk factors, such as crowded living conditions and exposure to indoor air pollution, as well as biological risk factors, such as malnutrition and underlying infections . These risk factors may drive the burden of influenza in South Africa to be greater than other countries with similar income level . In particular, Title: Risk factors for severe acute lower respiratory infections in children \u2013 a systematic review and meta-analysis", "Passage: Moreover, the odds ratio meta-estimates reported in this review should be useful for modeling the global, regional, and national estimates of severe ALRI if the national/regional prevalence of these risk factors are known . Future studies should investigate the role of poverty, HIV, and other risk factors currently classified \"likely\" or \"possible\" risk factors for ALRI, and should attempt to obtain more precise estimates of risk for \"definite\" risk factors by studying larger samples in diverse settings and by more careful measurement and analysis of possible confounding factors. Title: Risk factors for severe acute lower respiratory infections in children \u2013 a systematic review and meta-analysis", "Passage: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios : low birth weight 3.18 , lack of exclusive breastfeeding 2.34 , crowding -more than 7 persons per household 1.96 , exposure to indoor air pollution 1.57 , incomplete immunization 1.83 , undernutrition -weight-for-age less than 2 standard deviations 4.47 , and HIV infection 4.15 .", "Title: Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction\nPassage: This paper proposes a novel method to represent the potentiallyinfected group of people as a graph structure. We also model the principle of close proximity interaction by robustly analyzing the physical distance between subjects in the 3D world. This visionbased approach can re-identify diagnosed patients with infectious diseases and evaluate the infection risk of people who have contacted them. We evaluated our method in various scenarios, including indoor office, bus station, bus compartment, hospital. The comparison with the process of manual analysis shows that our method achieves consistent results but significantly reduces the time cost. Title: Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction", "Passage: The key contribution of our method is to quantitatively model the principle of Close Proximity Interaction , based on the state-of-the-art techniques in computer vision. The input to our workflow is video sequences VS i , i = 1, 2, 3, \u00b7 \u00b7 \u00b7 , N c , captured by multiple cameras. These cameras are potentially non-overlapping and installed at different locations. The search starts with a diagnosed patient P * , who is confirmed in the clinic with the pandemic disease. The goal of this work is to identify the contact graph and quantitatively evaluate their potential infection risk Title: Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction", "Passage: We use a graph representation to model the contact network. Each edge E is a sequence involving two subjects S A , S B as the graph nodes. Two nodes can be connected with multiple edges since two subjects can encounter each other at multiple locations. Title: Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction\nPassage: Inspired by the methods mentioned above, our method solves a multi-tasking problem by effectively taking advantage of the information from a few building blocks. Our method directly applies to real-world scenarios to identify potentially-infected subjects. So far, we found that this problem is under-explored.", "Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome\nPassage: Text: Multiple evanescent white dot syndrome was first described in 1984 as a rare, sudden onset of unilateral chorioretinopathy, with the predominant sign being multifocal yellow-white spots throughout the retina . The clinical spectrum of MEWDS has expanded over the years to include bilaterality and recurrences or an atypical presentation involving the fovea without the white spots . Symptoms include acute onset of decreased visual acuity unilaterally accompanied in most cases by photopsia and scotomata. A prodromal flu-like illness has been reported in up to 50% of cases . One report described a patient with elevated levels of total serum Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome", "Passage: The incidence of MEWDS is unknown. Only small case series are reported in the literature . One of the largest described 34 affected patients reviewed over several years' period . Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome\nPassage: Although MEWDS is suspected to occur as a consequence of a viral-like infection in genetically susceptible individuals, its precise pathogenesis remains unknown. Recovery is gradual, over weeks to months, and the visual prognosis is very favorable . Treatment is usually not required. Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome", "Passage: Abstract: OBJECTIVE: To describe an unusual cluster of multiple evanescent white dot syndrome encountered within a 3-month period. METHODS: This retrospective observation study is comprised of seven patients who presented with MEWDS in a 3-month period in central Israel. Data were collected from patients' medical records on clinical, multimodal imaging, and viral serology findings. RESULTS: Six women and one man of mean age 31.5 \u00b1 7.2 years. Three reported a precedent viral infection. All had unilateral decreased vision. Funduscopy revealed foveal granularity. MAIN IMAGING FINDINGS: Hyperfluorescent spots on blue autofluorescence , hypofluorescent spots on indocyanine green angiography, dark lesions on", "Title: Virus contaminations of cell cultures \u2013 A biotechnological view\nPassage: controlled conditions led to the production of better quality animals especially in respect of virus infections . Van Wezel et al. could show, by performing serological tests on 18 captive-bred cynomolgous monkeys and 40 imported wild caught parent animals that most of the wild caught animals were positive for antibodies against herpes simplex B, parainfluenza 3, or measles virus, whereas two thirds of the captive bred animals were only positive for antibodies against rotaviruses. Twenty out of 36 imported animals were positive for foamy virus 1 antibodies whereas these antibodies were not observed in the animals bred in captivity . Title: Model-Based Design of Growth-Attenuated Viruses", "Passage: Infections caused by viruses persistently threaten human health. For example, 40 million, 350 million, and 170 million people in the world are carrying human immunodeficiency virus type 1 , hepatitis B virus , and hepatitis C virus , respectively . Annually 5% to 15% of the global population is infected with influenza, resulting in 250,000 to 500,000 deaths . Protection against viral infections may be provided by inoculations with live-virus, killed-virus, or subunit vaccines. Live-virus vaccines offer advantages because they activate both humoral and cellmediated immunity, require only a single boosting, and generally provide longer immune protection than other forms Title: Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo", "Passage: Vaccination is the cornerstone control measure to reduce morbidity and mortality caused by infectious diseases. However, vaccination against hypervariable and emerging pathogens can be challenging. For example, seasonal influenza vaccines need to be updated almost annually to antigenically match emerging drift variant viruses and to maintain vaccine efficacy. Furthermore, in case of an emerging pandemic strain of influenza virus, timely production of a pandemic influenza vaccine has proven to be challenging 27, 28 . The rapid construction of recombinant viral vaccine vectors, such as MVA, which allows easy insertion of any or multiple antigens of choice and rapid production of Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Most, if not all, challenge viruses are manufactured according to Good Manufacturing Practice standard. Although controlled nasal inoculation differs from naturally occurring infectionin which exposure to variable quantities of the virus may occur at various mucosal sites -the developed HVC model used in challenge studies mimics natural disease as far as possible .", "Title: Global epidemiology of avian influenza A(H5N1) virus infection in humans, 1997 \u2013 2015: a systematic review\nPassage: a continuous threat to human populations, echoing the recommendations of WHO and other organizations on influenza at the human-animal interface, 41, 89, there is a need for sustained efforts and close collaboration between the animal health and public heath sectors at community, national, and international levels to monitor the dynamics in human, poultry and wild birds, and to conduct early clinical management, while downstream research is encouraged to develop vaccines and antivirals, explore the driving factors behind the epidemic, and evaluate the potential for future pandemics. Title: Clinical review: Update of avian influenza A infections in humans", "Passage: Avian influenza viruses have occurred with increased incidence within the human population, reflecting the delicate and tangled interaction between wildlife, domesticated animals, and humans. Disease in humans can be limited to conjunctivitis or an influenza-like illness, but HPAI H5N1 causes mainly severe pneumonia, respiratory failure, and death. Most cases have occurred through direct transmission from infected poultry or waterfowl, with only a few limited cases of human to human transmission. Treatment has been successful with the NA inhibitors if started early, and vaccine development is underway with a more immunogenic attenuated H5N1 virus preparation. Infection control measures are the mainstay Title: Global epidemiology of avian influenza A(H5N1) virus infection in humans, 1997 \u2013 2015: a systematic review", "Passage: America, and Asia, and so far no human cases of infection have been reported, with the exception of three human infections with influenza A virus detected in China in 2014-15. 39, 77 However, the co-circulation of influenza A viruses in human and animal reservoirs can provide opportunities for these viruses to re-assort and acquire the genetic characteristics that facilitate sustained human-to-human transmission, a necessary trait of pandemic viruses. 3, 87 Vaccines and antivirals are the most effective approaches to prevent influenza virus infection and treat illness respectively. 41, 88, 89 Vaccination of poultry has been implemented in many of the Title: Interventions in live poultry markets for the control of avian influenza: A systematic review", "Passage: Human influenza viruses cause seasonal influenza, a globally widespread respiratory illness giving rise to~3-5 million cases of severe illness every year . Influenza viruses can also be found in other mammals and birds, and the greatest diversity of influenza viruses occurs in aquatic birds . Most strains of avian influenza viruses do not pose a risk to human health. Some strains however, e.g. subtypes H7N9 and H5N1 , have acquired the ability to cross the speciesbarrier and infect humans who come into close contact with infected birds or contaminated environments . Occasionally, animal influenza viruses cause global pandemics in humans,", "Title: Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013)\nPassage: Crystallization Crystallization experiments and IDPs represent an inherent conflict, as crystallization requires very stable structures in order for diffraction to occur, and IDPs are very dynamic in nature. However, stabilizing these and other transient structures for the purpose of crystallization is possible, as demonstrated by the crystallization of Pup discussed earlier in this digest. Generally, crystallization of disordered proteins is facilitated by partners called 'crystallization chaperones'. A review by Bukowska et al. 76 summarizes the uses and applications of the most common crystallization chaperones and how they have been used to crystallize otherwise non-crystallizable structures. These approaches generally require other Title: Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein", "Passage: Protein crystallization. Crystals of the S-crystallin Q108F mutant in complex with GSH were obtained at 22 \u00b0C by the sitting drop, vapor diffusion method. Initial crystal screens were set up after incubating the protein at 6 mg/ml in 7 mM GSH and 0.35 mM CDNB for 1 h. Poorly diffracting crystals were grown in 0.5% PEG8000, 0.1 M HEPES, pH 6.8 and 1.65 M ammonium sulfate in 3 days and these were used for microseeding. Single crystals of a hexagonal shape and with dimensions of 0.15 mm were obtained in less than a week. All crystals were cryoprotected in reservoir Title: Lys-315 at the Interfaces of Diagonal Subunits of \u03b4-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly", "Passage: Introduction \u03b4-Crystallin is a taxon-specific eye lens protein. It is the major soluble protein in the eye lens of reptiles and birds and functions as a structural protein to maintain the refraction properties of the lens . \u03b4-Crystallin and argininosuccinate lyase are homologous proteins. ASL is In this study, the effects of this interaction on the folding pathway of wild-type and mutant proteins were investigated using urea as a denaturant. The different distributions of dissociated component from wild-type and mutant proteins, as measured by sedimentation velocity experiment, suggests the quaternary structure dissociates in different ways for wild-type and mutant proteins. Title: Lys-315 at the Interfaces of Diagonal Subunits of \u03b4-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly", "Passage: A containing 10% glycerol and 1.2 M ammonium sulfate and eluted with a linear gradient to the same buffer lacking ammonium sulfate. The retained proteins were eluted at~0.3 M ammonium sulfate. Fractions were pooled and loaded onto S-300 Sephacryl column pre-equilibrated in 50 mM Tris-acetic acid buffer, pH 7.5. Fractions were analyzed by SDS-PAGE and protein concentrations determined by the method of Bradford . Proteins possessing a C-terminal His 6 tag were purified on Ni affinity column then desalted using a Sephadex G-25 column as previously reported .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: inflammatory responses mediated by NF kappa B . The effects on NF-\uf06bB expression appeared to be confined to prevention of its nuclear translocation after its attempted activation with lipopolysaccharide, LPS . In the cytoplasm of infected cells, N protein can be found in cellular P bodies where it sequesters and protects 5' caps. It may locate the caps through its interaction with DCP1, a key constituent of P bodies. During hantavirus infection, the viral RNAs become concentrated in P bodies, through their interaction with N and DCP1. The N protein demonstrates preferential protection of mRNAs engineered to prematurely terminate their Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses", "Passage: During early viral infection, different viral proteins transiently colocalize with PML on NBs before disrupting them ). The functional consequences of the altered localization of the PML NBs could be a specific viral strategy to block cellular systems that may hamper viral replication. Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses\nPassage: During early viral infection, different viral proteins transiently colocalize with PML on NBs before disrupting them ). The functional consequences of the altered localization of the PML NBs could be a specific viral strategy to block cellular systems that may hamper viral replication. Title: The role of viral persistence in flavivirus biology", "Passage: Hantavirus infections are another interesting example of viral persistence. Hantaviruses are segmented, RNA viruses that cause lifelong infections in their reservoir rodent hosts, despite high levels of neutralizing antibodies . Pathogen recognition receptors, such as RIG-I and TLR7, are not elevated in the lungs of infected rats, suggesting that evasion of viral recognition may contribute toward the establishment of a persistent infection. Perhaps, the reason for noninduction of RIG-I is the fact that hantaviruses do not produce detectable amounts of dsRNA . IFNs, such as IFN-b, IFN-k, MxA, and pro-inflammatory chemokines, cytokines, and transcription factor genes are elevated midway in", "Title: Estimating the number of infections and the impact of non-\nPassage: others. Title: Self-Interest versus Group-Interest in Antiviral Control\nPassage: effects. For instance, it is well-documented that oseltamivir frequently leads to nausea and a number of less frequent adverse effects such as hepatitis and skin reactions . Recently, there have been suggestions of more serious adverse effects, including neuropsychiatric syndromes that may have contributed to a number of suicide events in Japan . Table 1 While we have used mortality as the currency to compare the costs and benefits of antiviral drug use, previous game theoretical studies of vaccination focused on the relative perceived risk of vaccination as compared to infection, and thereby also introduced a common currency to compare Title: What Effect Did the Global Financial Crisis Have Upon Youth Wellbeing? Evidence From Four Australian Cohorts", "Passage: Matching did result in a decline in the size of effects and the number that were statistically significant. However, eight out of 12 wellbeing factors remained significant, and of those only three had effects sizes greater than .10; namely career prospects, home life, and people in general . Importantly, however, these results tended to be smaller than the comparison at age 19 but generally not significantly so. Indeed, z tests suggested only satisfaction with living standards, independence, and social life had significantly larger effects at age 19 that 22. Title: Lost in Translation (LiT)", "Passage: One important item that is often overlooked in early human studies is accurate recording of symptoms using a volunteer or patient completed questionnaire, before and during a drug response. Symptoms represent a record of the input from the subjects' own sensory systems, gut, brain, etc., that are often more sensitive than anything else available. Some symptoms are common, for example, headache, often ascribed to caffeine deprivation, but others such as sedation, sleep disturbance, inattention, nausea, abdominal discomfort, diarrhoea and unusual fatigue are early clues to a pharmacodynamic effect. These concerns are often not reported by patients or by carers and", "Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1\nPassage: Since MAPKs are activated by phosphorylation, dephosphorylation of MAPKs seems to be an efficient process to inactivate their activities. It can be achieved by specific protein kinase phosphatases which can remove the phosphate group from MAPKs. Examples of these phosphatases include tyrosine phosphatases, serine/threonine phosphatases, and dual-specificity phosphatases . Some DUSPs are also known as MAPK phosphatases . Currently, there are at least 10 MKPs identified, while MKP-1 is the most studied member of the family. The regulatory role of MKP-1 on cytokine induction is best demonstrated by MKP-1 knockout macrophages in response to lipopolysaccharide , a cell wall component Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1", "Passage: Since MAPKs are activated by phosphorylation, dephosphorylation of MAPKs seems to be an efficient process to inactivate their activities. It can be achieved by specific protein kinase phosphatases which can remove the phosphate group from MAPKs. Examples of these phosphatases include tyrosine phosphatases, serine/threonine phosphatases, and dual-specificity phosphatases . Some DUSPs are also known as MAPK phosphatases . Currently, there are at least 10 MKPs identified, while MKP-1 is the most studied member of the family. The regulatory role of MKP-1 on cytokine induction is best demonstrated by MKP-1 knockout macrophages in response to lipopolysaccharide , a cell wall component Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1", "Passage: Western blot was done as described . Equal amounts of protein were separated by 10% SDS-PAGE, electroblotted onto nitrocellulose membranes , and followed by probing with specific antibod-ies for Actin, MKP-1 , phospho-p38 MAPK, phospho-ERK1/2 . After three washes, the membranes were incubated with the corresponding secondary antibodies. The bands were detected using the Enhanced Chemiluminescence System as per the manufacturer's instructions. Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1\nPassage: Western blot was done as described . Equal amounts of protein were separated by 10% SDS-PAGE, electroblotted onto nitrocellulose membranes , and followed by probing with specific antibod-ies for Actin, MKP-1 , phospho-p38 MAPK, phospho-ERK1/2 . After three washes, the membranes were incubated with the corresponding secondary antibodies. The bands were detected using the Enhanced Chemiluminescence System as per the manufacturer's instructions.", "Title: Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection\nPassage: Listeria monocytogenes is a Gram-positive, facultative intracellular, food-borne pathogen that causes severe disease in pregnant and immunocompromised hosts . L. monocytogenes is also an important model organism that has been used for decades to study bacterial pathogenesis, immunology and cell biology . Title: An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression", "Passage: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All protocols were reviewed and approved by the Animal Care and Use Committee at the University of California, Berkeley . Title: An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression\nPassage: For surface associated proteins, bacteria were suspended in 150 \u03bcL of LDS buffer containing 5% BME, boiled for 20 minutes, and proteins separated by SDS-PAGE. Title: An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression\nPassage: of these genes is regulated post-transcriptionally in response to the host.", "Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients\nPassage: Importantly, RASs to NS5B inhibitors were observed in 5 strains out of 26 sequenced samples . C451R was found in two isolates while A421V was found in only one. In 2 of the 3 strains for which we were able to obtain longer sequences, RASs S556G and Q556R were observed. Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients\nPassage: Importantly, RASs to NS5B inhibitors were observed in 5 strains out of 26 sequenced samples . C451R was found in two isolates while A421V was found in only one. In 2 of the 3 strains for which we were able to obtain longer sequences, RASs S556G and Q556R were observed. Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: RASs to NS5A inhibitors were identified in 2 strains out of 25 fully sequenced samples. RAPs were found in 3 strains : 2 exhibited the substitution H58P and 1 the substitution K24Q. Although these substitutions were not reported as resistant, some changes at these positions were previously described as RASs in subtype 1a, namely H58D and K24R . Finally, substitution E62D was found in one subtype 1a strain. This change is considered as a secondary substitution because, although it does not confer resistance by itself, when combined with a known RAS it does. In fact, it confers a higher level Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: RASs to NS5A inhibitors were identified in 2 strains out of 25 fully sequenced samples. RAPs were found in 3 strains : 2 exhibited the substitution H58P and 1 the substitution K24Q. Although these substitutions were not reported as resistant, some changes at these positions were previously described as RASs in subtype 1a, namely H58D and K24R . Finally, substitution E62D was found in one subtype 1a strain. This change is considered as a secondary substitution because, although it does not confer resistance by itself, when combined with a known RAS it does. In fact, it confers a higher level", "Title: Designing and conducting tabletop exercises to assess public health preparedness for manmade and naturally occurring biological threats\nPassage: with its known epidemiology, can undermine the credibility of the exercise and can distract participants enough to take them out of their roles, thus disrupting the flow of the exercise. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: Public distrust in journalists and the sensationalising of health related stories can also be a hindrance to taking the risk seriously and of undertaking precautionary measures . A belief that risk has been exaggerated is associated with an increased sense of helplessness and frustration and a reduction in the likelihood that people will prepare in the short-term . Title: Can informal social distancing interventions minimize demand for antiviral treatment during a severe pandemic?", "Passage: We have not explicitly considered school closure in any of these scenarios nor have we considered behavioural changes such as hand hygiene or coughing into your sleeve as the impact of these at a population level is difficult to quantify. We assume a constant level of behaviour change over some duration of time which is likely unrealistic. Some individuals may fatigue such that the magnitude of their behaviour change wanes over time. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The reluctance to be vaccinated and the cynicism illustrated by these extracts is consistent with research showing that decisions to engage in preventive and avoidant behaviours is influenced by attitudes towards public health interventions including having confidence in the efficacy of the behaviour . It is worth noting that the latter beliefs influence the level of trust in health agencies and that specifically advising people about why specific preparations are required increases the likelihood of adoption and helps maintain trust in health agency sources of information .", "Title: The lifecycle of the Ebola virus in host cells\nPassage: GP protein is synthesized in the endoplasmic reticulum as a precursor and transported along the classical secretory pathway from the ER via the Golgi apparatus to the plasma membrane. Precursor GP is processed by the acylation, oglycosylation, and maturation of N-glycans, and finally undergoes proteolytic cleavage by furin . Acylation is another posttranslational modification of viral GP, involved in particle formation, including virus assembly and budding. After those processes, GP is partially recruited to the late endosome to meet with VP40 for assembly and budding . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: During virus maturation, the precursor form GPC is processed using a membrane -bound protease into Gn and Gc, a cleavage that occurs, and appears to be signaled, after the conserved peptide signal WAASA at the C-terminal of Gn . Although the two proteins can be expressed independently through transfection, they can be retained in the wrong cellular compartment ; they thus must be co-expressed to allow them stability so that the two can be assembled correctly in the Golgi . Title: The lifecycle of the Ebola virus in host cells", "Passage: Following endocytosis, the next steps consist of the uncoating and fusion of the viral membrane with the endosomal membranes. Precursor GP is cleaved by the host enzyme, furin in the Golgi apparatus, resulting in GP1, GP2, and additional proteins, including sGP, \u0394-peptide, and ssGP . GP2 is critical for membrane fusion, as it's composed of five domains: 1) a fusion loop; 2) an N-terminal heptad repeat region; 3) a C-terminal heptad repeat region; 4) a transmembrane region; and 5) a short cytoplasmic tail . The glycan cap of GP1 can interact with the internal fusion loop of GP2 to restrict Title: Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis", "Passage: Furthermore, other viruses become processed after assembly. For instance, assembled polioviruses present in autophagosomes, were shown to mature upon acidification of these vesicles prior to their fusion with lysosomes. This acidification induces the cleavage of poliovirus capsid proteins, an essential step for these virions to gain full infectivity . Interestingly, MVM and H-1PV virions were shown to colocalize with the late endosomal/lysosomal marker Lamp2 . This leads us to speculate that the maturation of these viruses may involve the induction of additional post-assembly capsid modifications in these compartments besides the above-mentioned Golgi-associated phosphorylations.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In humans, overt disease was given the name Middle East respiratory syndrome, with the acronym MERS. From intermittent animal-to-human spill-over events, the MERS-CoV spreads sporadically among people, causing more severe disease among older adults, especially males, with pre-existing diseases. The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers . Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: MERS-CoV is characterized by sporadic zoonotic transmission events as well as spread between infected patients and close contacts . Nosocomial outbreaks in health care settings-the result of poor infection control and prevention-are widely recognized as the hallmark of MERS . Superspreading events have been recorded in healthcare settings in Jordan, Al Hasa, Jeddah, Abu Dhabi and South Korea . Like other coronaviruses, MERS-CoV can be spread through person-to-person contact, likely via infected respiratory secretions . Transmission dynamics, however, are otherwise poorly understood . Bats are believed to be the natural reservoir of MERS-CoV, and dromedary camels can have the virus Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Repeatedly touched surfaces, such as door knobs, should be disinfected and cleaned regularly. Intimate personal contact, e.g., kissing, and sharing cups or eating utensils must also be avoided .", "Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China\nPassage: responsible for most episodes of ARTIs in children. 1 In the past decade, several new viruses associated with ARTIs such as human metapneumovirus , novel strains of coronaviruses , human bocavirus , WU polyomavirus and KI polyomavirus have been discovered in human respiratory tract specimens. Among them, some have been identified to be causative pathogens of ARTIs. 1, 4, 5 Currently, there are no approved vaccines or medications available for most of the respiratory viruses. 1 A better understanding of the epidemiology of viral respiratory tract infections in children plays a key role for the prevention, control and treatment of Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: Text: Acute respiratory tract infections are a persistent and pervasive public health problem in both developed and developing countries. They cause a great burden of disease worldwide. Especially in developing countries including China, ARTIs, mainly pneumonia, are the leading cause of death among children under the age of 5 years. 1,2 A great variety of pathogens can cause ARTIs, and viruses have been considered as the predominant pathogens in this children population. 3, 4 The most frequently reported viruses include respiratory syncytial virus , influenza viruses A and B , parainfluenza viruses , human rhinovirus and adenovirus , which are Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: viral distribution patterns. 24, 29, 33 Regardless of the IAV outbreak, RSV and HRV were the two most common viral pathogens in ARTIs, which was consistent with most previous studies. 1, 10, 15, 16, 22, Our study further confirmed the importance of RSV and HRV in children with ARTIs, especially in children < 4 years of age. 10, 14, 23 Our results also showed that 12\u00c17% of viral pathogens detected were PIV1 and PIV3, which implied that PIVs played an important role in children with ARTIs. Similar findings were obtained in the studies conducted in Shanghai, 14, 34 Changsha, 26 Title: Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China", "Passage: infections . Studies of CAP have traditionally focused little on viral causes . Currently, viral infections are also involved with 80% of episodes of CAP in children under 2 years old and over 40% of older children . The existing studies have showed that respiratory syncytial virus and influenza viruses are important pathogens among the hospitalized and outpatient children presenting with ARTI .Adenovirus virus and parainfluenza viruses are also associated with a substantial proportion of ALRI in infants and young children .", "Title: Viral vector-based influenza vaccines\nPassage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adenovirus vectors are attractive as vaccine vectors because their genome is very stable and there are a variety of recombinant systems available which can accommodate up to 10 kb of recombinant genetic material . Adenovirus is a non-enveloped virus which is relatively stable and can be formulated for long-term storage at 4 \u00b0C, or even storage up to six months at room temperature . Adenovirus vaccines can be grown to high titers, exceeding 10 1\u00b0 plaque forming units per mL when cultured on 293 or PER.C6 cells , and the virus can be purified by simple methods . Adenovirus vaccines Title: HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach", "Passage: Adenoviral vectors have been used for a variety of vaccine applications including cancer and infectious diseases . Ad vectors have been utilized as vaccine vectors because of several attributes. This broad utility profile has derived from several key attributes: the viral genome is readily manipulated allowing derivation of recombinant viruses; replication-defective Ads can be derived and propagated easily in complementing cell lines making production of large scale vaccines feasible; Ads infect a broad range of target cells ; they possess a large gene delivery payload of up to 8kb; and the vector can achieve unparalleled levels of in vivo gene Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: both CD4 + and CD8 + T cell responses . The adenovirus vector is another of the most widely evaluated vectors to date to express heterologous antigens, due to ease of production, safety profile, genetic stability, the ease of DNA genome manipulation, and the ability to stimulate both innate and adaptive immune responses and induce both T and B cell responses . They have been extensively examined as a delivery vector in several preclinical and clinical studies for infectious diseases such as anthrax, hepatitis B, human immunodeficiency virus -1, influenza, measles, severe acute respiratory syndrome , malaria and tuberculosis M.", "Title: Responding to the COVID-19 pandemic in complex humanitarian crises\nPassage: Populations affected by humanitarian crises are expected to be particularly susceptible to COVID-19, the disease caused by SARS-CoV-2, due to displacement, crowded housing, malnutrition, inadequate water, sanitation, and hygiene tools, and stigmatization. Disease outbreaks further reduce access to limited healthcare, which is increasingly disrupted by attacks on health facilities and the persistent overburdening of health systems. These situations escalate both the necessity and the difficulty of delivering accurate and actionable information to potentially affected populations . Title: Responding to the COVID-19 pandemic in complex humanitarian crises", "Passage: As the international community responds to SARS-CoV-2, public health authorities in humanitarian crises begin at a disadvantage to enact appropriate infection control to prevent transmission in healthcare settings, identify infectious cases, administer supportive care and novel treatments for the seriously ill, and trace contacts. These standard public health measures are particularly difficult to perform in humanitarian settings. For example, limited public health, laboratory, and primary care services represent a barrier to testing. Providing the limited healthcare worker cadre with appropriate training and personal protective equipment, and ensuring a continuous supply chain for such, is a challenge in all settings, exacerbated Title: Responding to the COVID-19 pandemic in complex humanitarian crises", "Passage: in complex humanitarian crises. Frequent displacement and limited contact information may prevent effective contact tracing. Finally, intractable structural challenges such as overcrowding limit the implementation of both quarantine of those exposed and isolation of those who are ill. Given these increased vulnerabilities, humanitarian crises should be viewed as a priority for national and international bodies that seek to combat this unfolding pandemic. Resources must be identified to protect healthcare workers, develop and deploy rapid testing, improve surveillance, and enact quarantine and isolation of contacts and cases. Title: Innovations in research ethics governance in humanitarian settings\nPassage: or other difficult circumstances, where there is great vulnerability and pressing humanitarian needs.", "Title: Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species\nPassage: Previously, several studies were conducted on synonymous codon usage bias in a wide variety of organisms including prokaryotes and eukaryotes , and till date in many organisms the codon usage patterns have been interpreted for diverse reasons. Many genomic factors such as gene length, GC-content, recombination rate, gene expression level, or modulation in the genetic code are associated with CUB in different organisms . In general, compositional constraints under natural selection or mutation pressure are considered as major factors in the codon usage variation among different organisms . Moreover, studies revealed that mutation pressure, natural or translational selection, secondary protein Title: Genome-Wide Analysis of Codon Usage Bias in Epichlo\u00eb festucae", "Passage: Studies of codon usage have determined that several factors may influence codon usage patterns, including mutational bias and natural selection. Analysis of codon usage patterns sheds light on the molecular biology of gene regulation, gene expression, secondary protein structure, selective transcription, and the external environment. Among these, the major factors that are responsible for codon usage variation among different organisms are compositional constraints under mutational pressure and natural selection . Title: A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity", "Passage: evolutionary optimization of codon sequences that minimizes the consequence of frameshift errors . Unlike missense errors, which are not necessarily destructive to proteins, frameshift errors are deleterious as premature termination often leads to nonfunctional translational products. Therefore, the ribosome must keep the correct reading frame for hundreds to thousands of codons during translation to ensure proper protein production. Title: A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity", "Passage: The discrepancy between the experimental FS rates and ribosomal occupancy suggests that the overall frameshift consequence cannot be extrapolated from the local region in a linear manner. To assess the natural reading frame accuracy of individual ribosomal steps, we took advantage of ribosome profiling data sets that permit determination of ribosome positions at a subcodon resolution . Similar to previous reports , the overall ribosome-protected fragments show a strong 3-nucleotide periodicity with approximately 70% of reads mapped to frame 0 . The remaining out-of-frame reads could be due to Using ribosome profiling data in HEK293 cells, the ratio of average", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: Currently, there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin. Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV was recently reported, which shared \u223c96% homology with the SARS-CoV-2 . However, as we know, the human SARS-CoV and intermediate host palm civet SARSlike CoV shared 99.8% homology, with a total of 202 single-nucleotide variations identified across the genome . Given that there are greater than 1,100 nt differences between the human SARS-CoV-2 and the bat RaTG13-CoV , which are distributed throughout the genome in a Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: naturally occurring pattern following the evolutionary characteristics typical of CoVs, it is highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species are the most revealing signs that SARS-CoV-2 evolved by natural evolution. A search for an intermediate animal host between bats and humans is needed to identify animal CoVs more closely related to human SARS-CoV-2. There is speculation that pangolins might carry CoVs closely related to SARS-CoV-2, but the data to substantiate this is not yet published . Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Evolution is stepwise and accrues mutations gradually over time, whereas synthetic constructs would typically use a known backbone and introduce logical or targeted changes instead of the randomly occurring mutations that are present in naturally isolated viruses such as bat CoV RaTG13. In our view, there is currently no credible evidence to support the claim that SARS-CoV-2 originated from a laboratory-engineered CoV. It is more likely that SARS-CoV-2 is a recombinant CoV generated in nature between a bat CoV and another coronavirus in an intermediate animal host. More studies are needed to explore this possibility and resolve the natural origin", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The goal of any vaccine is to protect against infection and disease, while inducing population-based immunity to reduce or eliminate virus transmission within the population. It is clear that currently licensed influenza vaccines have not fully met these goals, nor those specific to inducing long-term, robust immunity. There are a number of vaccine-related issues that must be addressed before population-based influenza vaccination strategies are optimized. The concept of a -one size fits all\u2016 vaccine needs to be updated, given the recent ability to probe the virus-host interface through RNA interference approaches that facilitate the identification of host genes affecting virus Title: Clinical vaccine development", "Passage: One of the most important aspects of vaccinology in the 21st century is the extension of the target population by the development of new vaccines against emerging infections, tumors, and chronic diseases. Ultimately, the goal of modern vaccination may be expressed as to prevent or to cure as many diseases with vaccination as possible. Rappuoli et al. presented this concept in a simple figure . Meeting this challenge requires increasing both the number of vaccine clinical trials in nontraditional populations worldwide and the scientific expertise necessary for the successful development of new vaccines . Many initiatives have been launched recently Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: vaccine would be one that induces both mucosal and systemic responses similar to those occurring under natural infection, leading to long-term protection against both disease and infection. Such a vaccine might increase public confidence and result in better vaccine uptake. Title: Vaccines for the future: learning from human immunology\nPassage: Vaccination has been one of the most effective measures to control infectious diseases in the 20th century. It is believed that vaccination saves 2-3 million lives per year globally. Smallpox has been eradicated worldwide and polio is almost eliminated. Most of the viral and bacterial diseases traditionally affecting childhood all over the world are now preventable with vaccines and hepatitis B virus , which in some cases cause cancer. In summary vaccination has been -and continues to represent -a success story . However, there is still a long list of viruses , human immunodeficiency virus , Dengue, respiratory syncytial virus", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: The economic impact of major outbreaks can be substantial for the affected country. This was seen clearly in SARS, MERS in RoK and Ebola in West Africa. One analyst estimates that the current coronavirus outbreak's likely impact will range from a 0.8% cut to real GDP if the epidemic is controlled within 3 months, to a 1.9% cost to GDP if the epidemic lasts 9 months . This may increase substantially in the light of the extended restrictions on movement, and therefore trade and commerce, within China. Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: However, the 2009 pandemic, albeit milder than previous pandemics in terms of overall mortality, resulted in significant strains on global healthcare networks and economies . In Canada, direct healthcare costs related to the 2009 pandemic have been estimated at $2 billion CAD, with $250 million CAD related directly to hospital care . A computational modeling study by Smith and colleagues suggested that direct costs related to illness would be between 0.5-4.3% of GDP in the UK for pandemics ranging from low to extreme . Further, the 2002-2004 severe acute respiratory syndrome outbreak resulted in~$1 billion total GDP loss in Toronto Title: Human H5N1 influenza infections in Cambodia 2005\u20132011: case series and cost-of-illness", "Passage: An influenza pandemic may not only result in significant loss of life but also have a substantial impact on the economy. The 2003 SARS outbreak demonstrated that even a disease with relatively limited health impacts can have a major effect on the economy of a region . The Asian Development Bank estimate the impact of SARS in East Asia was approximately US$18 billion and suggest that an influenza pandemic could be substantially more . Compared to SARS, HPAI has not significantly impacted tourism however it has been extremely damaging to the poultry industry . The cost to the poultry sector Title: Estimating the number of infections and the impact of non-\nPassage: countries between 7 and 43 million individuals have been infected with SARS-CoV-Z up to 28th March,", "Title: Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens\nPassage: We used the ''Insignia'' program , a bioinformatics on line tool developed in the Center for Bioinformatics and Computational Biology, University of Maryland to choose a specific DNA or RNA ''signature'' for targeted viruses. Comparative sequence analysis of the complete genomes was performed using mVISTA . Multiple nucleotide sequence alignments were then created to visualize the most conserved genome areas using MEGA4 . Title: DisCVR: Rapid viral diagnosis from high-throughput sequencing data", "Passage: and hence require the operator to have expertise in command line usage and an understanding of bioinformatics, which may be difficult to find in diagnostic settings. To our knowledge, the only tool that has been developed for ease of use and for application on computers with limited resources is Truffle . This is designed to screen for a limited set of user-specified viruses, comes preloaded with probe-sets for grapevine viruses, and cannot easily be updated for large sets of viruses from other hosts. Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: The Identify-Isolate-Inform Tool was initially developed for Ebola virus disease 10,11 and later adapted for measles, 12 MERS, 13 mumps, 14 Zika virus disease, 15 hepatitis A, 16 pertussis, 17 and scabies. 18 This novel tool for suspected 2019-nCoV patients provides frontline clinicians with a simple algorithm to manage an emerging disease. Identification of exposed patients with an epidemiologic risk factor within 14 days of symptom onset is a crucial first step. An automatic prompt in the electronic health record can be useful in assisting clinicians with early identification of patients at risk. Case definitions promulgated by the WHO 24 Title: The Microbial Detection Array Combined with Random Phi29-Amplification Used as a Diagnostic Tool for Virus Detection in Clinical Samples", "Passage: A common method of choice for clinical pathogen identification is polymerase chain reaction which is a sensitive and specific method. However, each PCR reaction only provides identification of one specific virus, or a group of related viruses. Thus, a clinical hypothesis regarding the suspected pathogen needs to guide the decision as to which PCR analyses to perform, resulting in a large number of PCR protocols needed to facilitate the identification of all human pathogens.", "Title: Mortality among patients with tuberculosis requiring intensive care: a retrospective cohort study\nPassage: Twenty four patients had pulmonary disease only, 21 had extrapulmonary disease only, and 22 had association of pulmonary and extrapulmonary disease. The most common symptoms were fever , loss of weight , cough , and neurologic ones . Reticular infiltrate was the most common radiographic finding, followed by consolidation . Forty six patients collected a sputum sample, of whom 25 were sputum-smear positive. Mycobacterial cultures were positive in 35 patients . In 9 , TB diagnosis was based on clinical, epidemiologic and radiographic findings. The median interval from hospital admission until initiation of treatment was 3 days . Title: Mortality among patients with tuberculosis requiring intensive care: a retrospective cohort study", "Passage: Of them, 62 had ARF and required MV. The mean age of all patients was 43.2 \u00b1 14.1 years and males slightly outnumbered female patients . A history of previous TB was present in only 6 patients . Comorbid illnesses were identified in 58 patients, with coinfection with HIV being the most common, present in 46 patients. The median CD4/ mm 3 count of these patients was 83 , and only 6 were receiving highly active anti-retroviral therapy at the time of hospitalization. A history of alcoholism was present in 25 patients and 20 were current smokers. Demographic and clinical Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: The most striking finding was that a large proportion of TB patients did not present consistent cough. Passive case finding is the routine practice in developing countries where sputum microscopy is performed to identify TB cases among people with persistent cough. A large proportion of TB cases may be missed using this method as 53% of bacteriologically confirmed cases and 45% sputum positive cases in this study had no persistent cough but were identified through abnormal CXRAY. Nearly half of bacteriologically confirmed cases reported no symptoms in the last six months. This finding, although initially surprising, is consistent with reports Title: Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study", "Passage: No aspect of TB diagnosis or treatment was different in survivors or nonsurvivors. Twenty-two pulmonary TB cases and 22 disseminated TB cases were equally distributed between the 2 groups . Tuberculosis was diagnosed from respiratory samples in the majority of cases. Thirty-two patients were diagnosed through direct visualization of the bacillus using the Ziehl-Neelsen technique ; the diagnosis was only made through culture of respiratory specimens in 5 patients. Bacteremia due to Mycobacterium tuberculosis was found in 6 patients. Eleven patients required invasive procedures for TB diagnosis, such as organ biopsy. The main TB regimens prescribed were per oral or", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult.", "Title: Sounding the Alarm: Health in the Anthropocene\nPassage: Another important aspect of limits to growth is the increasing scarcity of resources, including the scarcity of affordable energy for use by industry, individuals and households. This aspect has received some public health attention, including a special issue in the American Journal of Public Health . In recent years, the price of oil has fallen , leading some commentators to argue that such concerns are overstated. However, few experts argue that the current comparatively low price of oil can be long sustained. Title: Sounding the Alarm: Health in the Anthropocene\nPassage: Other forms of worsening resource scarcity include of phosphate, rare earths, helium and some metals. Additional aspects include a limit to the growth of crop yields , falling returns to increasing complexity , and imperfect co-operation. See Butler, 2015, for further review . Title: Local risk perception enhances epidemic control", "Passage: Given infinite resources, all three of the decision paradigms would markedly diminish an emerging outbreak. However, interventions may be constrained by limited supplies or lack of population access to medical countermeasures, such as vaccines or antimicrobials. Even social distancing measures, such as self-isolation, may be limited by economic necessity-the need to go to work, school or daycare-or care-giving obligations for extended family. While such limitations should be formally analyzed, our simple analysis suggests that the best paradigm for averting infections also requires the fewest resources. For example, for a flu-like R 0 of two, compare the local count strategy, where Title: Sounding the Alarm: Health in the Anthropocene", "Passage: This dilemma illustrates a less appreciated limit to growth. On the one hand, there may not be enough accessible, easily recoverable oil to fuel the global economy for more than a few more decades. But even if there is, the global capacity to safely absorb the carbon emissions released by the burning of this oil is itself critically limited. There is growing academic recognition, and also from some in business that much of the world's oil resources are effectively unburnable , or they would be in a world that prioritises the avoidance of highly dangerous climate change and the acceleration", "Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919\nPassage: In mid-August of 1918, reports suggesting a second wave of this severe illness began to surface . In some regions, primarily Northern Europe, the period between the end of the first wave and the beginning of the second wave was incredibly short, making the two waves almost indistinguishable . This second wave, occurring from September-November 1918, was responsible for the majority of illnesses and fatalities associated with the pandemic. Although the origins of the first wave continue to be debated, the origin of the second wave is generally agreed to be the harbour town of Plymouth in Southern England, which Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: A third and final wave of the pandemic appeared in most of the world in the early months of 1919 . This final wave generally overlapped the first wave in terms of regional distribution; however, it seemed to spare areas where the second wave had been especially severe. Overall, morbidity rates were lower throughout this final influenza wave; however, mortality rates are believed to have been just as severe as the second wave . Three successive annual winter post-pandemic recurrences occurred following the third wave of the pandemic with continually decreasing mortality rates, in particular within those 20-40 years of Title: 1918 Influenza: the Mother of All Pandemics\nPassage: third pandemic waves, are unknown. Title: Lessons learned from the 1918\u20131919 influenza pandemic", "Passage: Those who had suffered from the earlier spring infl uenza generally suffered less discomfort in the second wave which would occur in the early summer of 1918 in Europe, affecting the outcome of the war. The third and most deadly wave of the infl uenza would occur later that year in the late fall. Despite the obvious differences between the strains in each wave, it is suggested that the more virulent form of infl uenza was genetically derived from the spring infl uenza . The antigenic composition of the 1918 virus is related to the H1N1 viral group. Phylogenetic studies", "Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China\nPassage: The most striking finding was that a large proportion of TB patients did not present consistent cough. Passive case finding is the routine practice in developing countries where sputum microscopy is performed to identify TB cases among people with persistent cough. A large proportion of TB cases may be missed using this method as 53% of bacteriologically confirmed cases and 45% sputum positive cases in this study had no persistent cough but were identified through abnormal CXRAY. Nearly half of bacteriologically confirmed cases reported no symptoms in the last six months. This finding, although initially surprising, is consistent with reports Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: Participants with positive sputum smear specimens were classified as sputum positive cases. Those with positive smear or culture sputum specimens were classified as sputum bacteriologically confirmed cases. Those being culture negative with abnormal CXRAY suggestive of TB and having been ruled out from other diseases by clinicians and radiologists were classified as CXRAY suggestive bacteriologically negative cases. Due to resource limitations the recommendation of broad-spectrum antimicrobial agents to confirm the diagnosis of negative TB cases was not applied in this survey . Newly diagnosed cases were distinguished from previously diagnosed cases through checks during the interviews and against the TB Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: other suspects . The symptom consultation alone identified 308 suspects, including 6 sputum smear positive TB and 9 bacteriologically confirmed TB. Among the 344 suspects with CXRAY abnormalities, 11 had sputum positive TB and 18 had bacteriologically confirmed TB. The yield of bacteriologically confirmed cases was 47.4% by screening consultation and 94.7% by CXRAY. In the population of over 65 years old, symptom consultation and the CXRAY identified 174 and 182 suspected cases respectively, yielding5 and 9 of bacteriologically confirmed cases. Yields of bacteriologically confirmed cases were 55.6% by symptom consultation and 100% by CXRAY among over 65's. Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: All participants of the survey were first screened by symptoms and CXRAY. Those who had symptoms of consistent cough or haemoptysis, or CXRAY abnormalities were then screened by smear and culture. Case identification rates of new bacteriologically confirmed cases from the suspected cases were significantly higher with CXRAY as a primary tool and further increased by both symptom screen of persistent cough and CXRAY compared with symptom screen alone . The same pattern of case identification rate was observed in the sputum positive cases . The proportion reporting persistent cough was not significantly higher among bacteriologically confirmed cases compared with", "Title: It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919\nPassage: Text: Influenza and influenza viruses are wellknown popular topics to medical professionals and the general public. Influenza viruses had caused a pandemic globally during 1918 and 1919, and that influenza pandemic had taken away more than 20 million people's lives in the world. However, in my opinion, it is unlikely that influenza viruses will again cause a pandemic on a level comparable to what happened in 1918 and 1919. Title: Invasive bacterial infections following influenza: a time\u2010series analysis in Montr\u00e9al, Canada, 1996\u20132008", "Passage: well be in fact random variations in the parameters. The comparison of observed and expected S. pyogenes counts before and after influenza counts are added to the model shows a visible improvement in fit. A comparison of the two dark lines shows that, with influenza B in the model, four transient increases in S. pyogenes infections are now modelled that were not before: those in 1997, 2001, 2007 and especially 2008. Looking back at the time series of influenza B counts , one notes that these were years with late, high peaks in the weekly numbers of influenza B-positive tests. Title: 1918 Influenza: the Mother of All Pandemics\nPassage: Could a 1918-like Pandemic Appear Again? Title: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997\u20132006)\nPassage: One example of such possible viral persistence between influenza seasons was found, with HA and NA sequences from the same viruses , showing a similar clustering pattern for both these genes, separated by at least one year.", "Title: Estimating the number of infections and the impact of non-\nPassage: estimate that interventions across all 11 countries will have averted 59,000 deaths up to 31 March Title: Estimating the number of infections and the impact of non-\nPassage: in its epidemic, the recent interventions are forecasted to avert 370 total deaths up to 31 of March. Title: Estimating the number of infections and the impact of non-\nPassage: much earlier in its epidemic, we predict 370 deaths have been averted. Title: Estimating the number of infections and the impact of non-\nPassage: our intervention model, we calculated the total deaths averted up to the end of March. We find that,", "Title: HIV/AIDS prevention in China: A challenge for the new millennium\nPassage: Although positive steps have now been taken by the Chinese government in combating HIV/AIDS, numerous challenges remain. One issue is the structural inadequacy of China's current health care system that was graphically revealed during the SARS outbreak . Tuberculosis offers another pertinent example of how these shortcomings may compound the situation. China now has twice the level of multi-drug resistant tuberculosis of other countries . Providing affordable and accessible health care to the general public has also become increasingly difficult following the introduction of free-market reforms in 1978. In this manner, the rural health cooperatives that once provided health insurance Title: Preventing Emerging and Re-emerging Infections in the Eastern Mediterranean Region: Gaps, Challenges, and Priorities", "Passage: For malaria control, low coverage of diagnostic facilities for confirmation of malaria, weak malaria surveillance, limited capacity for developing a comprehensive plan for monitoring, prevention and management of insecticide resistance and limited preparedness to deal with natural and man-made devastations such as floods and civil unrest are current challenges. For vaccine-preventable diseases the main hindrances in achieving the immunization targets continue to be the emergency situations, varying technical and managerial capacity, varying strength of the health systems, the multiple priorities and insufficient government financial allocations, and low community awareness and attitudes towards vaccine. Title: Steps to a Sustainable Public Health Surveillance Enterprise A Commentary from the International Society for Disease Surveillance", "Passage: The significant health impacts and economic costs of disease outbreaks illustrate the critical importance of effective public health surveillance and rapid response, as well as the cost of inaction. 11 Table 1 provides examples of the health and financial burdens posed by some naturally occurring and intentional infectious disease outbreaks. The values reported in Table 1 do not fully reflect additional indirect costs of diseases and their potentially crippling effects on a community, nor do they address costs that are underreported/ unreported due to lack of data. Higher rates of illness, for example, can lead to lower worker productivity, 11 Title: Local risk perception enhances epidemic control", "Passage: As outbreaks emerge, public health agencies often implement a variety of pharmaceutical and non-pharmaceutical interventions to prevent epidemic expansion, including vaccination and medical prophylaxis, school closures and other social distancing measures, and information campaigns to promote awareness, hygienic precautions and voluntary isolation . However, such measures require population adherence and are often hindered by failure to take recommended actions . Around the globe, for example, seasonal influenza vaccine coverage falls significantly below the 75% baseline recommended by the World Health Organization, but varies widely between countries and across age groups . In the USA, 2015-2016 uptake was only 59.3% in", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: total of 3711 persons , 199 symptomatic cases have been diagnosed on board as of 24 February, and additional asymptomatic infections and symptomatic cases after disembarkation have also been reported. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Text: An outbreak of novel coronavirus disease has occurred on a cruise ship, the Diamond Princess . The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 and 766 cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards.", "Title: Chest radiographic data acquisition and quality assurance in multicenter studies\nPassage: Recruitment of study subjects began in May 1990 and continued through January 1994, with follow-up continuing through January 1997. At the time of this report, 3,057 chest radiographs had been performed on the children enrolled in this study. Title: The Trojan Chicken Study, Minnesota\nPassage: The study design was further limited in that we did not account for time after exposure when photographs were taken. Since participants could drop by any time of the day, the time after exposure and duration of exposure likely varied between participants. In both the feasibility and pilot studies, the return rate was low, and tracking down participants was difficult. If similar studies are conducted in the future, a reward system might be used to increase compliance. Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: This report describes a study planned while the pandemic was emerging in spring, 2009, with the hope of evaluating cross-protection. We established a cohort, collected baseline samples, monitored donors for symptoms, and collected follow-up samples. Banked samples were used to characterize pre-existing antibody and T-cell immunity cross-reactive with the pH1N1 virus and responses to infection. The relative mildness of the pandemic was fortunate for public health but resulted in relatively few infections in this cohort. We characterize baseline donor T-cell and antibody responses reactive with pH1N1 plus certain follow-up parameters. Title: Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1)", "Passage: responses. In contrast, the telephone-based study of Rubin et al. employed a random-digit-dial sampling design, allowing a more representative sample of the general UK population, but their sample was only 997 respondents and the survey was undertaken after media attention had abated, beginning 8 May 2009. Nonetheless, the results reported in this paper are largely congruent with our own results and we see the studies as strongly complementary.", "Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: Text: Q fever is a worldwide zoonosis caused by Coxiella burnetii , a small, gram-negative obligate intracellular bacterium. C. burnetii displays antigenic variation with an infectious phase I and less infectious phase II. The primary reservoir from which human infection occurs consists of sheep, goat and cattle. Although C. burnetii infections in animals are usually asymptomatic, they may cause abortions in sheep and goats . High concentrations of C. burnetii can be found in birth products of infected mammals . Humans frequently acquire infection through inhalation of contaminated aerosols from parturient fluids, placenta or wool . Because the infectious dose Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies", "Passage: C. burnetii is a highly pleomorphic Gram-negative coccobacillus and the causative agent of Q fever. Q fever is a zoonosis, and the most common reservoirs are cattle, sheep, and goats but many other animals can be infected by C. burnetii . When infected, these domestic animals can shed the organism in urine, feces, milk, and especially birth products. The pathogen survives within the phagolysosome of host cells, and a spore stage has been described. This spore stage explains the ability of C. burnetii to survive in unfavorable environmental conditions, and it can be an environmental risk for months to years Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: is very low and C. burnetii is able to survive in a spore-like state for months to years, outbreaks among humans have also occurred through contaminated dust carried by wind over large distances . Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3trimester and to test animals in petting zoos regularly for C. burnetii.", "Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection\nPassage: In conclusion, our study suggests that bacterial coinfection is not uncommon in H1N1 infected patients and laboratory investigations should go beyond establishing a viral cause alone. Bacterial coinfection was more frequently seen in the older age group and was associated with higher rates of complications. As adjunct to clinical findings, clinicians need to have a high index of suspicion if neutrophilia was identified on admission as it may denote bacterial coinfection. A larger scale study will be useful to further confirm our findings. Title: Severe novel influenza A (H1N1) infection in cancer patients", "Passage: In our study, we detected bacterial coinfection in seven of the eight patients. The CDC reported that 29% of fatal cases in the United States presented at least one bacterial coinfection . Mauad et al. found evidence of bacterial coinfection in 38% of fatal cases in Sao Paulo. Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: Forty-five patients had lower respiratory tract specimens sent for bacterial cultures. The 5 patients without these specimens were children who had difficulty in producing respiratory secretions, however, they appeared generally well with no evidence of pneumonia. Blood cultures were performed in 23 patients and Mycoplasma pneumoniae serology in 27 patients . Of the 50 H1N1 patients, 17 were coinfected with a second respiratory pathogen; 14 bacterial and only 3 viral. Mycoplasma pneumoniae was the commonest bacterial coinfection followed by Staphylococcus aureus , Klebsiella pneumoniae , Streptococcus pneumoniae , Moraxella catarrhalis , Pseudomonas aeruginosa , Streptococcus pyogenes and Streptococcus agalactiae . Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: The bacterial coinfection rate of 28% amongst our H1N1 hospitalized patients was higher compared to other studies . A large laboratory-based study in the United States demonstrated comparable bacterial coinfection rates to our study with similarly very low frequency of viral copathogen detection . Whilst our finding concurred with several studies that showed H1N1 infections having a predilection for younger patients, patients > 50 years had higher risk of bacterial coinfection in our study.", "Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection\nPassage: The intestinal epithelial barrier forms a selectively permeable immunologically tolerant but alert barrier between the sterile inside and microbe-laden lumen. Title: The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human\nPassage: of this system is apparent with the identification of different types of Goblet cells, which synthesize and secrete the mucus along the crypt in the human colon. Indeed a \"sentinel\" Goblet cell has been identified, positioned at the top of each colonic crypt. Endocytosis of TLR generates MUC2 secretion, together with an intercellular gap junction signal, which induces MUC2 secretion in adjacent Goblet cells and thus regulates the entry of bacteria into the crypt . Title: The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human", "Passage: The stability of the mucus barrier and the innate defense mechanisms rely on the secretion of intact, gel forming mucus and the availability of mucosal immune proteins, including immunoglobulins and the trefoil factor peptides. Together these factors normally ensure mucosal cell integrity and epithelial homeostasis through restitution and regeneration processes. Part of the risk is linked to the immature state of the mucosa at this very early stage of life. A role for the mucins in the pathogenesis of NEC is indicated by the depletion of Goblet cells seen in the mucosa of neonates with NEC and this is expected Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: homeostasis Similar to intestinal mucosal epithelial cells, lung epithelial cells have developed many defence mechanisms to deal with environmental exposures. Increasing evidence shows that the UPR pathways interact with the recognition and handling of exogenous threats, like viruses. 44 The continuous epithelium in the airways acts as a physical barrier to keep the underlying immune system separated from exogenous air-borne pathogens. Ciliated cells continuously clear inhaled matter trapped by the mucus layer. Respiratory goblet cells synthesise and secrete the mucins, MUC5B and MUC5AC rather than MUC2. MUC5B/AC, and their glycoforms contribute to the elasticity and viscous nature of the mucus", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: The analysis of the focus group data was undertaken by a single researcher who was neither present at the focus groups nor had read any preliminary findings. This work was verified by the focus group facilitators to ensure that any \"contextual richness\" had not been missed in the data. Thematic analysis was used to identify themes and concepts across the entire data set to \"identify repeated patterns of meaning\" . The process involved working through the six phases of thematic analyses as identified by Braun and Clarke . Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The study was part of a rapid response initiative; therefore focus groups were selected as the most efficient means of data collection in the time available. Eight semi-structured focus groups were recruited between May and July 2010 comprising 7 to 13 participants each and lasting approximately 1 hour. Separate focus groups were conducted for each of the target groups with a total of 80 participants representative of five target populations groups identified in consultation with Ministry of Health staff: M\u0101ori, Pacific Peoples, children , general population, and vulnerable people with chronic conditions (defined as those who are eligible for subsidised Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: Immunogenicity and Safety of an AS03-Adjuvanted H7N9 Pandemic Influenza Vaccine in a Randomized Trial in Healthy Adults", "Passage: increase . The coprimary safety objective was to describe the safety and reactogenicity of the vaccines up to day 42. Title: Safety of Tdap vaccine in pregnant women: an observational study\nPassage: SAEs were also reported to the Marketing Authorisation Holder as part of global drug safety surveillance. Title: The promise of mRNA vaccines: a biotech and industrial perspective", "Passage: As the field accrues more data from early-phase human studies, the focus of mRNA vaccines will shift from documenting local and systemic tolerability to capturing potential long-term safety. Unfortunately detecting safety signals for uncommon adverse events requires thousands of subjects. As with novel adjuvants, an adequate safety database to assure safety for candidate mRNA vaccines is likely to be in the tens of thousands range. Given that different manufacturers are pursuing different strategies to optimize their candidate vaccines, conclusions from one candidate may not be generalizable. Therefore, it is likely that each candidate vaccine will have to independently prove its", "Title: Timing and causes of death in septic shock\nPassage: ICU also directly resulted from end-of-life decisions in 36 patients with fixed multiple organ failure for whom the treating physicians were convinced that meaningful recovery was not possible. Therefore, extensive diagnostic procedures were not carried out in such settings of exclusive palliative care. Besides, most early-onset deaths were directly related to the primary infection through intractable shock and multiple organ failure . In addition, 6.4 % of early decedents were diagnosed with mesenteric ischemia likely to act as a consequence or a contributor of multiple organ failure. Most late deaths were related to ICU-acquired complications such as nosocomial infections and Title: Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study", "Passage: a high rate of fatality, with more than one fourth of the patients dying in hospital. The highest proportion of death occurs early in the course of the disease, despite an excellent proportion of initial adequate antibiotherapy . This is considered to be related to the early inflammatory process, which is overwhelming host defences. In a recent study, Garcia-Vidal et al. investigated independent factors associated with early deaths in CAP and demonstrated that age, altered mental status, multilobar pneumonia, shock, bacteraemia and inadequate empiric antibiotic therapy were predictors of death within 48 hours . The small number of patient dying Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Local elaboration of inflammatory and chemotactic mediators is considered to be a requirement for the development of systemic disease symptoms, with those abnormalities sometimes culminating in shock and death. Yet it is not hypoxemia, due to the prominent pulmonary edema, that leads to death in most fatal cases of HCPS, but rather intoxication of the heart by as-yet-undefined mediators that leads to the low cardiac output state and the associated shock syndrome . It is tempting to speculate that mediators produced in the lung in connection with the inflammatory infiltrate can percolate through the coronary circulation with minimal dilution in Title: Timing and causes of death in septic shock", "Passage: failure, the development of , digestive perforation . Others : myocardial infarction , lymphoma-related tumor lysis syndrome , extensive limb ischemia , acute liver failure . Iatrogenic complications related to chest tube insertion , catheter insertion , accidental removal of tracheostomy , and cardiac arrest at the start of hemodialysis . MOF multiple organ failure, ICU intensive care unit, ARDS acute respiratory distress syndrome sepsis-induced immunosuppression in patients that survive the primary insult may favor the development of secondary infections in addition to other common risk factors related to severity and requirements for invasive procedures . Ventilator-associated pneumonia remains the", "Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity\nPassage: HIV infectivity by increasing the viral mutation frequency . In a follow up study, Clouser et al. further reported the antiviral effect of gemcitabine against HIV-related retrovirus, murine leukemia virus , in vitro and even in murine AIDS model . A significant antiviral effect of gemcitabine on IAVs was also reported for RPE cells by Denisova et al. . They also tested whether gemcitabine had an antiviral effect on several other viruses of different families and found its strong inhibitory effect on Sindbis virus and herpes simplex virus-1 but relatively weak effects on Semliki forest virus and human echovirus 6, Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: and minimal effects on Bunyamwera virus, measles virus , and vaccinia virus . The antiviral effect of gemcitabine on EVs, initially performed on Coxsackievirus B3 , was found from screening FDA-approved drugs in CVB3 replicon-harboring Vero cells by our group . Its broad-spectrum antiviral activity on EVs was further identified by observing a similar inhibitory effect on enterovirus 71 and human rhinoviruses . In the case of HRV, the antiviral effect of gemcitabine was further confirmed in a virus-infected mouse model . In this study, intranasal administration of gemcitabine significantly lowered the pulmonary viral load and inflammation by decreasing proinflammatory Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: can infect pregnant women and cause congenital abnormalities such as microcephaly in infants, which has attracted increasing public attention as well as extensive research and development into possible treatments. Effective antiviral activities of gemcitabine were also found for the replication of HCV in Huh-7 cells and the infection of HIV in U373-MAGI-CXCR4 CEM cells, with estimated EC 50 s of 12 nM and 16.3 nM, respectively , which were lower concentrations than those used in cancer therapy . In the case of HIV, the combination of gemcitabine with decitabine, another nucleoside analog in clinical use for cancer therapy, synergistically reduced Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: Most studies regarding the antiviral activity of gemcitabine lack experimental evidence of the mode of action. However, our group has recently reported that gemcitabine had an anti-EV effect by targeting the salvage pathway of pyrimidine biosynthesis . Moreover, gemcitabine strongly induced the expression of several ISGs including CXCL10, IRF7, IRF9, IFIT1, and DDX58, which were the major effectors in the innate immunity that defended the host against the virus infection. These results were consistent with a previous report that gemcitabine stimulated the production of IFN-\u03b2 and IFN-\u03b3 in IAV-infected RPE cells . Importantly, the activation of ISGs was well-correlated with", "Title: Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak\nPassage: Third, the decline in reproduction number could be because many infections were asymptomatic and many symptomatic cases were not reported. The request to report any symptoms might not have reached all participants because of the event's large size and because participants came from many different countries. During norovirus outbreaks, asymptomatic cases occur; in almost half of the outbreaks in the Netherlands during 2002, stool samples from >1 healthy persons tested positive for norovirus . Volunteer and outbreak studies demonstrate that 30% of collected stool specimens of exposed, asymptomatic persons were positive for norovirus . However, both the proportion of asymptomatic Title: Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan", "Passage: the number of people in each category for each outbreak, genotyping results were obtained. Figure 1 summarizes the survey results, and the coded data are given in eTable 1. It should be noted that the number of asymptomatic and virusnegative individuals includes both uninfected individuals and infected cases without virus shedding. The abovementioned study 31 has been very rigorous, in that all individuals involved in each food-borne outbreak were fully surveyed, which has been extremely rare and not routinely attainable. In addition, such a study must employ the highly sensitive real-time RT-PCR, a condition that was also satisfied by the Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1", "Passage: initial cases could arise from individuals who are asymptomatic, but still carrying and transmitting the virus or from others whose illness was not sufficiently acute to warrant seeking medical attention. To our knowledge, the issue of the impact of this misspecification of the number of cases on the estimation of epidemic parameters has not been well-studied. Title: Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan", "Passage: It should be noted that q was assumed as independent of symptoms because the RT-PCR testing employed was highly sensitive and the cut-off value must have allowed q to be comparable between symptomatic and asymptomatic infected individuals. 8, 26 Sensitivity analysis was conducted to address potential difference of q between symptomatic and asymptomatic infection . It should also be noted that the parameter p should have ideally reflected the demographic stochasticity of the data generating process, but p is a mixture of food-borne and human-to-human transmissions and we do not have a sufficient dataset to characterize the distribution. Thus, the", "Title: High Throughput Screening for Small Molecule Enhancers of the Interferon Signaling Pathway to Drive Next-Generation Antiviral Drug Discovery\nPassage: To achieve simultaneous treatment of cells with IFN-b and various compound concentrations and to avoid reagent degradation over time, the screen was run in a modular manner with a precise timeline . The first step included production of plates with appropriate concentrations of compound and IFN-b and then storage at 4uC. A separate plate was made for each of the four compound concentrations . The Twister II, Sciclone, Orca, and Liconic cold storage incubator handled this step. For the second step, cells were plated at 8000 cells per well in 384-well assay plates . This step was accomplished in seven Title: High Throughput Screening for Small Molecule Enhancers of the Interferon Signaling Pathway to Drive Next-Generation Antiviral Drug Discovery", "Passage: concentrationresponse were rejected. Compounds with a consistent increase or decrease in response with increasing drug concentration or good efficacy at any concentration were included for further validation. This approach led to selection of 64 compounds for further validation, including compounds with the 20 highest z-scores. Title: High Throughput Screening for Small Molecule Enhancers of the Interferon Signaling Pathway to Drive Next-Generation Antiviral Drug Discovery", "Passage: Thereafter, to reach a smaller and tractable set of hits to validate experimentally, we took advantage of testing each compound at four concentrations. Specifically, we used self-organizing maps analysis to cluster hit compounds by shape of the dose-response curve. The significance of change from dose to dose was also analyzed using linear models and moderated F-statistics as implemented in the limma package in Bioconductor . The concentration-response curves for each compound were then visually inspected, using scatter plots generated in TIBCO Spotfire DecisionSite , with respect to the shape of the curve and reproducibility between replicates. Compounds showing an erratic Title: Identification of Novel Compounds Inhibiting Chikungunya Virus-Induced Cell Death by High Throughput Screening of a Kinase Inhibitor Library", "Passage: High-throughput screening is a technology widely used in today's drug discovery programs that aims to speed up the identification of potentially active substances against various diseases. By using high-throughput assays, a large collection of substances, from small molecules to natural products, can be evaluated for antiviral activity in a relatively short amount of time . The work reported here describes the development of a simple, cell-based high-throughput assay to screen potential CHIKV antivirals. The assay uses resazurin, an oxidized, nonfluorescent blue dye that is converted to the reduced, and highly fluorescent pink-colored resorufin through oxidation-reduction reaction, to measure cellular metabolic", "Title: Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis\nPassage: The controversies surrounding BSE and the seal deaths show two aspects of Osterhaus' role. He was self-confident in his estimations about risks, but also acknowledged criticism from his sceptics. The tricky question was when to stick to his original position, and when to adopt the opposing view, and, consequently, the appropriate strategy. This, he says, created a tension: on the one hand he had his own gut feelings, and at the same time he tried to think through competing viewpoints. There was not only an epistemological choice to be made, but also a balancing act to carry out: considering various Title: Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study", "Passage: Competing interests FB received a speaker fee from BRAHMS. ER receives research support from the National Institute of Allergy and Infectious Disease and the Aggennix Corporation and has served as one-time consultant for Aggennix Corporation, Eisai Pharmaceuticals, Idaho Technologies and Astra Zeneca. RB has received research support, consulting fees, and honoraria from BRAHMS and from bioMerieux. DA has received consultant fees from BRAHMS, performed PCT assays for the PCT-7 trial, and had access to equipment and assays by BRAHMS as part of NIH-funded studies. KR has received consultant fees from BRAHMS. FMB has received consultant and speaker fees and grant/research Title: Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk", "Passage: In adopting a quasi-foundational approach, there are ways to ensure rigour and the trustworthiness of interpretations. The social phenomenology of Schutz, used to derive themes and as a basis for theory development from respondent perceptions, requires meeting three postulates, namely logical consistency, subjective interpretation and adequacy. For the first, we have highlighted how the research problem and methods were derived from a real world problem on which was based the questionnaire, sampling strategy and the need to interview; for the second, by using respondents' views to develop interpretation ; and for the third, by linking second order constructs to activities Title: Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients", "Passage: The proportion of bacteria in the SBA group was 96.0% , higher than that of the SAA group ; while the proportion of fungi isolated from the SAA group was 8.4%, higher than that of the SBA group . The ratio of gram-positive bacteria isolated from the SBA group was slightly more than that isolated from the SAA group , while separation rate of gram-negative bacteria was not statistically different between the two groups .", "Title: Tuberculosis mortality: patient characteristics and causes\nPassage: course and died in less than 14 days. Among the 27 patients diagnosed ante-mortem, the median interval between the initial visit and starting anti-TB treatment was 12 days , and 16 of these patients had received anti-TB treatment for \u226514 days before death. The median interval from treatment initiation to death was 23 days . Title: Estimation in emerging epidemics: biases and remedies\nPassage: The WHO Ebola Response Team report that the average time from symptoms to death is 5 \u00fe 4 \u00bc 9 days, while to remission the average time is 5 \u00fe 12 \u00bc 17 days. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: subsequently spreads to another . Among those with progressive illness, the median time to death is 11 to 13 days, ranging from five to 27 days . Fever and gastrointestinal symptoms may form a prodrome, after which symptoms decline, only to be followed by a more severe systemic and respiratory syndrome . Title: Tuberculosis mortality: patient characteristics and causes\nPassage: On the other hand, even among patients whose TB was diagnosed ante-mortem, the median time from treatment initiation to death was short. This finding was similar to that of previous reports, in which many patients died of TB within a short period of time, ranging from 1 week to 3 months after starting treatment . It was speculated that these patients were too ill on arrival and their outcomes could not be reversed even after treatment . The initial tentative diagnosis of our fatal TB patients was bacterial pneumonia in 39.5%, and sepsis or other severe infections in 20%, suggesting", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: viral load respectively were similarly inconsistent across available literature. Convalescent plasma, while promising, is likely not yet feasible, given the limited pool of potential donors and issues of scalability. Monoclonal antibody treatment is progressing. SARS-CoV enters host cells through the binding of their spike protein to angiotensin converting enzyme 2 and CD209L . Human monoclonal antibodies to the S protein have been shown to significantly reduce the severity of lung pathology in non-human primates following MERS-CoV infection . Such neutralizing antibodies can be elicited by active or passive immunization using vaccines or convalescent plasma respectively. While such neutralizing antibodies can Title: Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients", "Passage: The absence of viremia in both patient categories and relatively low viral load in the lung aspirates of the critically ill patients suggest that enhanced replication of the virus may not be an important contributor to the pathogenesis . The viral load in lung aspirates was independent of fatality. In contrast, among the Spanish patients , 93% and 57% of the mild and critical cases respectively were positive for serum viral RNA, with no significant difference in the viral load. Both studies used CDC primers for real time PCR and the critical cases were bled when already on Oseltamivir treatment, Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: well-tolerated in healthy participants. Where the biological samples are taken from also play a role in the sensitivity of these tests. For SARS-CoV and MERS-CoV, specimens collected from the lower respiratory tract such as sputum and tracheal aspirates have higher and more prolonged levels of viral RNA because of the tropism of the virus. MERS-CoV viral loads are also higher for severe cases and have longer viral shedding compared to mild cases. Although upper respiratory tract specimens such as nasopharyngeal or oropharyngeal swabs can be used, they have potentially lower viral loads and may have higher risk of false-negatives among Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Serological testing such as ELISA, IIFT and neutralization tests are effective in determining the extent of infection, including estimating asymptomatic and attack rate. Compared to the detection of viral genome through molecular methods, serological testing detects antibodies and antigens. There would be a lag period as antibodies specifically targeting the virus would normally appear between 14 and 28 days after the illness onset . Furthermore, studies suggest that low antibody titers in the second week or delayed antibody production could be associated with mortality with a high viral load. Hence, serological diagnoses are likely used when nucleic amplification tests are", "Title: Assessment of Temporary Community-Based Health Care Facilities During Arbaeenia Mass Gathering at Karbala, Iraq: Cross-Sectional Survey Study\nPassage: In most countries, the WHO has a country office led by a WHO Representative . The WRO provides the most important link between the WHO and the affected country for the purposes of gathering technical information, providing the local context in which an event takes place to WHO, conveying the opinions and preferences of the country to WHO regional and central headquarters, and relaying relevant information back to the affected country. During an MG event, the WRO's role in the event management process includes the following: Title: Psychological Flexibility of Nurses in a Cancer Hospital: Preliminary Validation of a Chinese Version of the Work-related Acceptance and Action Questionnaire", "Passage: The WAAQ is a seven-item scale that measures psychological flexibility in relation to the workplace. The items reflect the extent to which people can take goal-directed action in the presence of difficult internal experiences. The items are rated on a seven-point Likert-type scale ranging from 1 to 7 . Higher scores indicate greater levels of work-related psychological flexibility. The WAAQ has shown a satisfactory one-factor structure, reliability , as well as external, convergent, concurrent, and predictive validity. For instance, in comparison with the AAQ-II, the WAAQ correlates more strongly with work-specific variables. Title: A multidimensional classification of public health activity in Australia", "Passage: An ontology defines a common vocabulary for researchers who need to share information in a domain. It includes machine-interpretable definitions of basic concepts in the domain and relations among them . Title: Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development\nPassage: COA is an ordination technique that identifies the major trends in the variation of the data and distributes genes along continuous axes in accordance with these trends. COA creates a series of orthogonal axes to identify trends that explain the data variation, with each subsequent dimensional factor explaining a decreasing amount of the variation . Each ORF is represented as a 59-dimensional and each dimension is related to the RSCU value of each triplet . This was done using the CodonW program.", "Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking\nPassage: Text: With the ability to directly bind to DNA and regulate the expression of adjacent genes, nuclear receptors are a class of ligand-inducible transcription factors. They regulate various biological processes, such as homeostasis, differentiation, embryonic development, and organ physiology . The NR superfamily has been classified into seven families: NR0 ; NR1 , NR2 , NR3 , NR4 , NR5 , and NR6 . Since they are involved in almost all aspects of human physiology and are implicated in many major diseases such as cancer, diabetes and osteoporosis, nuclear receptors have become major drug targets , along with G protein-coupled Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking", "Passage: With the ability to directly bind to DNA and regulate the expression of adjacent genes, nuclear receptors are a class of ligand-inducible transcription factors. They regulate various biological processes, such as homeostasis, differentiation, embryonic development, and organ physiology . The NR superfamily has been classified into seven families: NR0 ; NR1 , NR2 , NR3 , NR4 , NR5 , and NR6 . Since they are involved in almost all aspects of human physiology and are implicated in many major diseases such as cancer, diabetes and osteoporosis, nuclear receptors have become major drug targets , along with G protein-coupled receptors Title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features", "Passage: Nuclear receptors are ligand-activated transcription factors that regulate the activation of a variety of important target genes, which are the most important drug targets in terms of potential therapeutic application. According to our results, secondary structure and polarizability play the major role in determining the drug-NRs interactions. The conservative motif of the NR is typically described as three stacked alpha-helical sheets. The helices that make up the ''front'' and ''back'' sheets are aligned parallel to one another. The helices in the middle sheet run across the two outer sheets and only occupy the space in the upper portion of the Title: Marine Organism Cell Biology and Regulatory Sequence Discoveryin Comparative Functional Genomics", "Passage: Mechanisms by which expression of a single gene is regulated can be extremely complicated. Multiple phosphorylation-or ligand-dependent nuclear receptors that homo-or heterodimerize may be required to achieve activity. Each of these receptors may have different activation specificity or duration, even when acting via the same regulatory DNA sequence such as classical proximal promoter elements. These receptors may also work in combination with other transcription factors that function at sites more distal from the proximal promoter or in introns. Alternatively spliced transcripts represent another complex aspect of gene expression regulation that is influenced by extracellular and intracellular signaling but is not", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Camel calving season occurs in the winter months and this may be a time when there is increased risk to humans of spill-over due to new infections among na\u00efve DC populations . What role maternal camel antibody might play in delaying infection of calves remains unknown . Juvenile DCs appear to host active infection more often than adult DCs and thus the sacrificial slaughter of DCs, which must be five years of age or older , may not be accompanied by significant risk of exposure to infection. In contrast to earlier results, slaughterhouse workers who kill both younger and older Title: Extreme water-related weather events and waterborne disease", "Passage: may also increase the risk of flooding in many areas, increasing human exposure to waterborne pathogens . Droughts or extended dry periods are known to reduce the volume of river flow and potentially increase the concentration of effluent-derived pathogens, due to reduced dilution by stream-receiving waters . Title: The interconnected and cross-border nature of risks posed by infectious diseases\nPassage: been linked to the hunting or slaughtering of primates and other wild animals . The density and health of livestock, meanwhile, have been linked to disease in humans . Although inconclusive, there is some evidence to suggest that livestock production may lead to increased antibiotic resistance in human pathogens. There are certainly many pathways by which drug resistant pathogens could transmit from livestock to humans, including environmental contamination by excreted veterinary antibiotics . Title: Predicting wildlife reservoirs and global vulnerability to zoonotic Flaviviruses", "Passage: their ability to pose ongoing spillover risk to humans.", "Title: Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review\nPassage: Papers were clustered according to the methodology used. More precisely, for each paper we identified the list of technical keywords associated with the methods, including both general concepts and sub-analysis terms ; the full list of technical keywords is presented in the Supporting Information, S1 Table. Papers that share the same keyword are often connected. Consequently, analytical 2) What methods have been used? Ascertain the key epidemiological methods developed and used so far. Classify the methods in terms of general approaches: such as descriptive phenomenology, process based models , statistical analysis of empirical data etc. Title: Pandemic influenza in Papua New Guinea: a modelling study comparison with pandemic spread in a developed country", "Passage: method. Title: Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review\nPassage: The statistical methods used to fit a model with the observed data were assessed with information criteria in almost 20% of cases. In a significant proportion of papers , the validation of the method was based on out-of-sample predictions, i.e. a subset of the data were used to train/calibrate the method , and then the method was applied to the rest of the data. In some cases, there was no assessment of the methods. Situations where the methods did not require comparison with real data were also present. Title: Operationalising resilience in longitudinal studies: a systematic review of methodological approaches\nPassage: used by the original authors.", "Title: Hepatitis C Virus Non-Structural Protein 3 Interacts with Cytosolic 5\u2032(3\u2032)-Deoxyribonucleotidase and Partially Inhibits Its Activity\nPassage: Hepatitis C virus is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma . Infection with HCV is also etiologically involved in the development of B-cell lymphomas . This virus belongs to the genus Hepacivirus in the family Flaviviridae. The HCV genome is a single, positive-stranded RNA with a nucleotide length of about 9.6 kb. It encodes a polyprotein precursor of approximately 3,000 amino acids. This polyprotein precursor is processed by host and viral proteases into at least 10 different proteins, which are arranged in the order of NH2-C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH. C, E1, and E2 are structural proteins while NS2-NS5B Title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver", "Passage: in the HCV protein levels was observed in the mice treated with LC16m8, rVV-CN2, or rVV-CN5. These results indicated that HCV nonstructural proteins might be important for effects of therapeutic vaccines. In contrast, rVV-CN5 which encoded HCV structural and non-structural proteins did not show any significant effects. These results indicated that HCV structural proteins might have inhibited the therapeutic effects of the non-structural proteins. Therefore, it may be important to exclude the HCV structural proteins as antigenic proteins when developing therapeutic vaccines against chronic hepatitis C. Title: Hepatitis C Virus Non-Structural Protein 3 Interacts with Cytosolic 5\u2032(3\u2032)-Deoxyribonucleotidase and Partially Inhibits Its Activity\nPassage: For the detection of endogenous HCV NS3 and cellular cdN proteins, HCV subgenomic RNA replicon cells were used . Title: Hepatitis C Virus Non-Structural Protein 3 Interacts with Cytosolic 5\u2032(3\u2032)-Deoxyribonucleotidase and Partially Inhibits Its Activity", "Passage: HuH7 cells were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum , 100 U/ml penicillin and 100 mg/ml streptomycin . HCV sub-genomic replicon cells were cultured in DMEM with 10% FBS, 100 U/ml penicillin, 100 mg/ml streptomycin and 400 mg/ml G418 . All cultured cells were maintained at 37uC with 5% CO 2 .", "Title: Th17 profile in COPD exacerbations\nPassage: COPD is characterized by a continuous inflammatory process of the airways, leading to obstruction or limitation of airflow, which is mainly associated with exposure to cigarette smoke. 1, 2 However, only 10%-20% of smokers will develop the disease at some day in their life. These data lead to the belief that this disease is due to multiple factors that interact with each other. Among the most prominent are genetic factors that can condition patients to have a certain susceptibility to COPD. For example, deficiency of alpha1-antitrypsin is present in at least 1% of the carriers of the disease in Europe Title: Th17 profile in COPD exacerbations", "Passage: two or more exacerbations per year, where the best predictor will be the history of previous treatments for exacerbations. 10 Indeed, about half of COPD patients die after 4 years of their first episode of exacerbation. 11 The symptomatology of COPD is diverse, depending on the phenotype . However, there is a range of signs and symptoms that occur more frequently, such as dyspnea of small efforts, chronic cough and increased sputum production. In addition, other clinical data that may appear are hypoxemia, hypercapnia, the so-called \"chest in barrel\" , weight loss, etc. 6, 10, 48 Molecular mechanisms in COPD Title: Asthma in the elderly: what we know and what we have yet to know", "Passage: The symptoms of asthma and COPD are very similar, if not identical. The major differences are the degree of reversibility is often greater in asthma and the persistence of dyspnea is greater in COPD. Both are characterized by exacerbations which respond to corticosteroids and bronchodilators, infections triggering exacerbations, episodic wheezing, cough with or without mucous production, improvement with chronic inhaled corticosteroids and bronchodilators, and decreased exercise tolerance. The chronic bronchitis phenotype of COPD as opposed to the emphysematous phenotype is more likely to be confused with asthma, but the variations of phenotypes in both diseases confounds simple measures to reliably Title: Th17 profile in COPD exacerbations", "Passage: The Global Initiative for Chronic Obstructive Lung Disease defines COPD as a common and treatable disease characterized by the persistent limitation of airflow, which is usually progressive and associated with an increase in the inflammatory response in the airways and in the lungs by harmful particles and gases. 10 Also, this guide defines exacerbations as an acute event characterized by worsening of patient's respiratory symptoms that go beyond daily variations and leads to a change in medication. 6, 10, 48 In addition, the guide also points out that a patient with frequent exacerbating COPD will be considered when he has", "Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: Targeting viral RNAs is the most direct and effective way to curb hantaviral replication. Small interfering RNA directed against hantaviral genes could facilitate viral RNA clearance based on the RNA interfering mechanisms and has been tested as a potential antiviral strategy in vitro and in vivo. It has been demonstrated that siRNAs targeting the S, M, or L segment of ANDV could reduce viral replication in Vero E6 cells or human lung microvascular endothelial cells and that an S-targeted siRNA pool seemed to be more efficient in reducing viral transcription and replication than M-or L-targeted siRNA in Vero E6 cells. Title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development", "Passage: A total of 5 \u00d7 10 5 A549 cells were seeded into six-well plates, allowed to reach confluence, and then challenged with virus . Total RNA was extracted from cells using the TRIzol reagent . Following phenol-chloroform extraction and isopropanol precipitation, the RNA pellet was washed, dried, and dissolved in 20 mL of RNase-free water. The protocol of RT-PCR amplifications and Q-PCR were as described by Hsu et al 38 . Title: Viral RNA extraction for in-the-field analysis", "Passage: Retroviruses encode their genetic information in RNA molecules, and have a high genomic recombination rate, which allows them to mutate more rapidly and thereby pose higher risk to humans. International travel and rising population densities render infectious retroviruses such as HIV, severe acute respiratory syndrome virus, hepatitis virus and influenza virus serious health threats to the public worldwide. A clear example is the recent virulent strain of avian flu , which has the potential to transcend the species barrier and become a deadly infectious disease for humans. One important way to help combat these viral infectious diseases is early detection Title: Frontiers in antiviral therapy and immunotherapy", "Passage: Opening this CTI Special Feature, I outline ways these issues may be solved by creatively leveraging the so-called 'strengths' of viruses. Viral RNA polymerisation and reverse transcription enable resistance to treatment by conferring extraordinary genetic diversity. However, these exact processes ultimately restrict viral infectivity by strongly limiting virus genome sizes and their incorporation of new information. I coin this evolutionary dilemma the 'information economy paradox'. Many viruses attempt to resolve this by manipulating multifunctional or multitasking host cell proteins , thereby maximising host subversion and viral infectivity at minimal informational cost. 4 I argue this exposes an 'Achilles Heel' that", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: The E1-A226V mutation also enabled an increase in infectivity of Ae. albopictus when compared to its infectivity of Ae. aegypti , and with several factors taken together, Ae. albopictus has become the new preferred and more lethal vector for CHIKV . In fact, Tsetsarkin et al. found that a Green Fluorescent Protein tagged E1-A226V virus was 100 times more infective to Ae. albopictus than it was to Ae. aegypti . In all the Indian Ocean Islands, Ae. albopictus became the main vector for CHIKV within 1-2 y after CHIKV was introduced to the region . Title: Dengue Fever, Hawaii, 2001\u20132002\nPassage: Ae. albopictus was the vector responsible for the 2001 Hawaii outbreak. Both entomologic surveys support that Ae. albopictus is ubiquitous, often common on all the islands, whereas Ae. aegypti is restricted to a few small foci on the relatively sparsely inhabited island of Hawaii. Title: Dengue Fever, Hawaii, 2001\u20132002", "Passage: where Ae. aegypti is present. Compared with Ae aegypti, Ae. albopictus is considered to be an inefficient epidemic dengue vector because it is less anthropophilic and not as well adapted to urban domestic environments . Ae. albopictus will readily feed on humans, but usually only on a single person, and it also feeds on other animals, which decreases the probability of human contact . Lifestyle factors may also help explain why Hawaii's dengue outbreak was limited . Residences in many affected areas often had dense, uncultivated vegetation near housing and, not infrequently, an abundance of items that could serve as Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: The 2005-2006 epidemic of CHIKV in La Reunion islands in the Indian Ocean, spurred the discovery of a new vector species, Ae. albopictus . Wrecking over one-third of the island's population, this epidemic peaked its devastation between January and February 2006, when over 46,000 cases came into light every week, including 284 deaths . Ae. albopictus is common in urban areas of the United States and is already flourishing in 36 states, raising grave concerns to the immunologically naive populace of the United States .", "Title: Identification of MicroRNA-Like RNAs in Mycelial and Yeast Phases of the Thermal Dimorphic Fungus Penicillium marneffei\nPassage: protein. RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules involved in mitosis, while cytochrome P450 catalyses diverse reactions in fungal primary and secondary metabolism, and xenobiotic detoxification. As for PM-milR-M2, 20 potential targets were predicted, which include 13 transposon or transposable elements and seven conserved hypothetical proteins. Title: Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease", "Passage: In addition to RNA Polymerase I, optimal rRNA gene transcription requires a number of accessory factors that facilitate Pol I recruitment, initiation, promoter escape, elongation, termination and re-initiation . Pol I transcription begins with the formation of the preinitiation complex by the upstream binding factor and the TBP-containing complex selectively factor at the rDNA promoter. SL-1 confers promoter sequence specificity by recognizing the core promoter element and it promotes a stable interaction between UBF and the rDNA promoter . In turn, UBF binds the upstream and core promoter elements as a dimer, possibly looping the intervening DNA into a nucleosome Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: The out:in ratios were calculated by dividing the number of RPFs mapping within 5 leaders of a transcript by the number of RPFs mapping to the coding region of the transcript including the translation initiation codon . Read coverage was length normalized by nucleotide length of the respective feature . 5 leader:AUG ratios were calculated by dividing the number of RPFs mapping within the 5 leaders of a transcript by the number of RPFs mapping to the start codon of a transcript or non-canonical start codons. Read coverage was length normalized by nucleotide length of the respective feature. Title: Proteomics Analysis of the Nucleolus in Adenovirus-infected Cells", "Passage: DBP implies that it may be an accessory factor in viral DNA replication during viral infection. Notably, in interphase cells, UBF and Nopp140 are co-localized and are known to be recruited together . RBM4 has been reported to be either predominantly nuclear or predominantly nucleolar, depending on experimental conditions . In our hands, the protein was nucleolar in \u03fe80% of cells. RBM4 has been implicated in the modulation of splice site selection, something of clear relevance to adenovirus infection, but it has also FIG. 4 . Distribution of proteins identified by SILAC as being enriched in nucleolus during viral infection.", "Title: Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel\nPassage: A total of 180 cases and 532 controls were included in the study population. Eight cases could only be matched to 2 controls. Table 1 shows the distribution of cases and controls by demographic factors. Overall, about 83% were males, 49% were whites, 44% were blacks, over 57% were younger than 25 years, 10% were older than 35 years, about 12% were Hispanic, and over 56% were in the army. Approximately 35% of cases had greater than 3 years of military service. Title: CDC Summary 21 MAR 2020,\nPassage: cases in the United States by age group found that 80% of deaths were among adults 65 years and older with the highest percentage of severe outcomes occurring in people 85 years and older. Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology", "Passage: in all case definitions by 137 respondents , in the majority of case definitions by 248 , and in the minority by 11 . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: Klosterneuburg in Austria in 2017 with 1.57 million basepairs . Pithovirus sibericum is the largest among giant viruses discovered to date with a diameter of 1.5 microns, a genome of 470,000 bp with 467 putative genes, 1.6 microns in length, and it is presumably 30,000 years old as it was recovered from permafrost in Siberia . The smaller Pandoraviruses with 1 micron in length have five times larger genomes, 2,500,000 bp . Title: Evolution of Genome Size and Complexity in the Rhabdoviridae", "Passage: Substantial variation in genome size and complexity was also observed in many rhabdovirus genera, suggesting that the length of the genome is not heavily constrained in all members of the family. Indeed, the presence of new ORFs and/or very long stretches of non-coding sequence within or between transcriptional units was noted frequently. Previous observations have demonstrated that foreign genes of up to~6 kb can be inserted into the VSIV genome without significant disruption to viral replication in vitro . Expanded VSIV genomes were morphologically similar but proportionally longer than wild-type viruses, suggesting that the unique morphology of the rhabdovirus particle Title: Evolution of Genome Size and Complexity in the Rhabdoviridae", "Passage: may more readily accommodate genome expansion than other virion structures. A significant body of evidence suggests that genome size in RNA viruses is likely to be constrained by low replication fidelity , and a relationship between genome size and error rate has been observed in a diverse array of organisms . However, if the genome sizes of rhabdoviruses are constrained by selective pressures other than those imposed by the background mutation rate, genome expansion may not require a concomitant reduction in polymerase error rates. As the mutation rate of rhabdoviruses has only been determined experimentally for VSIV thus far ,", "Title: Herpes zoster encephalitis presenting as multiple cerebral hemorrhages \u2013 a rare presentation: a case report\nPassage: Examination of peripheral blood smear failed to demonstrate any malarial parasite. The result of a rapid malaria antigen test was negative. The cerebrospinal fluid examination revealed: lymphocytes with presence of red blood cells , protein 90mg/dL, and glucose 108mg/dL. There was no organism in Gram and Ziehl-Neelsen staining of the CSF. His hemogram showed a total leukocyte count of 12,700/\u03bcL . His platelet count, bleeding and coagulation profile were within normal limits. The results of the human immunodeficiency virus tests were negative by both enzyme-linked immunosorbent assay and rapid HIV test for HIV-1 and HIV-2 antibodies. Title: Clinical study of children with cryofibrinogenemia: a retrospective study from a single center", "Passage: In this study, patients with CNS involvement presented as large artery narrowing, parenchymal involvement, and hemorrhage in demyelinating lesions on the white matter and basal ganglion. The last is compatible with acute hemorrhagic encephalomyelitis , considered a hyper-acute sub-form of acute disseminated encephalomyelitis. It is frequently a fulminant inflammatory hemorrhagic demylination of the CNS white matter. Death from brain edema is common within one week of the onset of encephalopathy. The pathogenesis is known as acute vasculitis with subsequent vessel occlusion . The patient here with AHEM presented with consciousness disturbance and repeated seizures. Herpes simplex virus infection is identified Title: Hemorrhagic shock and encephalopathy syndrome \u2013 the markers for an early HSES diagnosis", "Passage: Although abnormal cerebral edema was seen in all the patients during their clinical courses, 5 patients appeared normal or only slightly edematous as revealed on their brain CT scans upon admission. On the initial EEG, multi-focal paroxysmal discharges were seen in 4 patients, and low-amplitude patterns were seen in 4 other patients. The CSF cell counts were within a normal range in 7 patients, while the serum level of IL-6 and soluble IL-2 receptors increased with varying ranges in all the patients . Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: syndrome such as high blood pressure. Macrophage activation syndrome could also lead to acute necrotic brain injury. However, it is associated to high ferritin and low triglycerides at the time of the encephalopathy, other multisystemic injuries, typical neuropathological findings, and recurrence over time, which were not noted in our patient . Parvovirus B19 has been described to cause encephalopathy in sickle cell patients. It is associated with aplastic anemia. It caused punctate areas of hemorrhages in the basal ganglia, periventricular white matter, and mainly along the posterior parietal cortex. This was attributed to parvovirus B19-induced vasculitis . In our patient,", "Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")\nPassage: the website http://www.swinefluques tionnaire.com. The website link was pasted onto a variety of general, non-health networking websites . Respondents were primarily from the UK and Portugal but also included 30 respondents living outside these countries and resident in Finland , Poland , Malta and France . Ten non-European based residents were then removed from the online survey before analysis. Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: The current outbreak of swine infl uenza that originated in Mexico in March 2009 has spread to more than 80 countries causing more than 3,99,232 laboratory confi rmed cases of pandemic infl uenza H1N1 globally and over 4735 deaths reported to World Health Organization as of 11 October 2009 . The WHO declared pandemic alert stage 6 on 11 June 2009, indicating an ongoing infl uenza pandemic . The 2009 swine fl u virus designated H1N1 A/swine/California/04/2009 is not zoonotic swine fl u and is not transmitted from pigs to humans, but rather from person to person and has higher Title: Clinical aspects and cytokine response in severe H1N1 influenza A virus infection", "Passage: Originating from Mexico and spreading initially in the United States and Canada, a novel influenza A virus infection ) of swine origin spread globally during spring 2009 to mid-February 2010. Rates of hospitalization and death have varied widely according to country . Among hospitalized patients 9 to 31% have been admitted to intensive care units where the rate of death was 14 to 46% . Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: with confi rmed swine fl u . This new strain of H1N1 swine infl uenza has a unique combination of genes from both North American and Eurasian swine lineages that has not been identifi ed previously in either swine or human populations . The virus appears to be a result of reassortment of two swine infl uenza viruses, one from North America and one from Europe with the North American virus itself the product of previous re-assortments, carrying an avian PB2 gene for at least 10 years and a human PB1 gene since 1993. The virus also has genome segments", "Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections\nPassage: The second indicator of disease severity we consider is the time to peak viraemia. Several studies have shown that high viraemia levels early in infection are associated with a higher risk of developing severe disease . For primary infections, a shorter time to peak viraemia is associated with higher disease severity, while peak viraemia is rarely observed during a secondary infection, suggesting that virus peaks earlier in secondary infection relative to a primary infection . Figure 5b shows that our models recover this described negative relationship between time to peak viraemia and the peak level of endothelial activators. In secondary Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: for peak viraemia or the time to peak viraemia, because viraemia levels from patients with secondary dengue infection are generally already in decline by the time patients are admitted . Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: We first sought to determine whether the minimal model capable of reproducing the features of a primary dengue infection could reproduce the above features of a secondary dengue infection. To recover a secondary infection's shorter time to viral peak and higher level of peak viraemia, a 20% increase in the viral infectivity rate b was sufficient, resulting in a peak viraemia level of 9.8 log 10 viral copies at 7.4 days post viral inoculation. This level and timing of peak viraemia is consistent with virological data from secondary DF and DHF patients . This reparametrization can also be easily interpreted Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: The first virological indicator of disease severity we consider is peak viraemia. A higher magnitude of viral load early in infection has been repeatedly associated with a higher risk of developing severe disease . When a viral peak is observed, higher values of peak viraemia are associated with a higher risk of developing severe disease . Figure 5a shows that our models reproduce the observed positive association between peak viral load and peak endothelial cell activator levels. Furthermore, figure 5a shows that during a secondary infection, both peak viral load and peak E levels are generally higher than in a", "Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury\nPassage: Hepcidin is a \u03b2-defensin-like antimicrobial peptide that is mainly produced by the liver. Hepcidin not only shows antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and yeasts, but also functions as a principal iron regulatory hormone . Hepcidin binds to the iron export protein ferroportin and induces its internalization and degradation, which leads to decreased cellular iron export and increased intracellular iron retention . Because iron is an essential nutrient for all organisms, hepcidin also restricts the iron available to invading microbes, thereby enhancing the host defense against pathogens . Furthermore, hepcidin can modulate the lipopolysaccharide -induced acute inflammatory response via Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: Hepcidin is bound to plasma alpha-2 macroglobulin . Evidence suggests that other cells may express the hepcidin mRNA at a much lower level than the hepatocytes; the biological significance of the extra hepatic production of hepcidin remains uncertain. Plasma hepcidin is freely treated through glomeruli and in animals with normal kidney activity it quickly passes through the urine. In addition, a part of hepcidin is cleansed through degradation along with ferritin . Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: the regulation of iron hemostasis. This peptide prevents iron absorption from the small intestine and releases iron from reticuloendothelial cells. In infectious diseases, macrophages and bacteria compete to absorb iron . Macrophages interfere with the absorption of iron by bacteria. Eventually, the pathogen does not grow and replenish. Factors that cause hepcidin production are increased in bone marrow and anemia. Other factors that increase the production of hepcidin are iron accumulation and inflammation . Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: Hepcidin is effective on iron transfer from macrophages. In the presence of hepcidin, ferritin is transmitted into the macrophage and is destroyed by lysosomes, resulting in storage of iron inside the cell. In low concentrations of hepcidin, ferritin is present in the cell membrane, allowing the release of iron. After leaving the cell, iron oxide is rapidly oxidized by ceruloplasmin, a copper-rich ferroxidase and converted into ferric iron and then bound to transferrin .", "Title: A bibliometric analysis of literature on malaria vector resistance: (1996 \u2013 2015)\nPassage: are used and recommended for IRS . Title: A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan\nPassage: sample material. Title: A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan", "Passage: Our compendium provides a perspective that can help draw a roadmap for a scientific research program when the project outputs and metrics are incorporated. In addition, aligning program objectives and exacting expectations across participants and stakeholders contribute to the roadmap that ultimately builds that partner country's capability and capacity necessary for sustainability. Tracking the evolution of program projects and studies, especially collaborations and networks, is emphasized to capture important activities that are often omitted when large programs evolve and institutional memory is lost through turnover of human resources. To advance science through increased transparency and mature capabilities, a multi-sectoral approach, Title: A bibliometric analysis of literature on malaria vector resistance: (1996 \u2013 2015)", "Passage: extracted the information as is from Scopus. However, due to different spelling of authors or institutions, it is possible that some authors have multiple affiliations that the authors were not aware of and thus the ranking might not be 100% accurate. Finally, in VOSviewer, we always used a minimum number or threshold to draw the maps, thus not all the items are shown. Not being shown in the map does not mean that the item is not important or that the authors were biased toward any particular item. The authors were aware of all these limitations and did their best", "Title: A Global Champion for Health\u2014WHO\u2019s Next?\nPassage: Chan will step down from WHO on June 30, 2017 after more than a decade in the post. The process for choosing WHO's next leader has begun, promising to be protracted and rigorous as befits the importance of the role. Factoring in the many influential stakeholders in the process of appointing Chan's successor, however, transparency of the selection process may be one area unlikely to attract plaudits. Although too soon to speculate about the identity of WHO's next Director-General, it is worth reflecting on what qualities an incoming leader should bring to WHO and how that person might need to Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: Instead of electing a new Director-General, Lorenz Von Seidlein of Mahidol University, Thailand, argued that \"the problems. . .are now so deeply ingrained that replacing the WHO with new, more appropriate organizations is the logical solution. . .at a fraction of current cost, free of cumbersome, archaic obligations and entitlements and an ability to respond to new problems.\" This viewpoint is indicative of the strength of feeling that WHO's deficiencies have come to evoke in some of those committed to the cause of improving the health of people in low-income and middle-income countries. But this perception acknowledges that an accountable Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: during March 17-28, the WHO Director-General declared on March 29, 2016 the end of the Public Health Emergency of International Concern regarding the EVD outbreak in West Africa . Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: WHO's next Director-General should be a proven leader and advocate, perhaps from a lowincome or middle-income country. The new recruit will be greeted by a full in-tray, and featuring prominently are likely to be the constraints imposed by WHO's current funding mechanisms. A substantial proportion of WHO's existing budget is earmarked for specific projects, leaving the organization with little financial flexibility to respond to unanticipated demands. However, any improved funding mechanism is likely to follow, and be dependent on, organizational reform. According to Kruk, \"WHO is both essential and hamstrung. . .the election of the Director-General should be a moment", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: The shorter nucleocapsid or N protein is a structural component of the viral nucleocapsid, along with the genomic viral RNA segments. As an RNA-binding protein that engages the hairpin termini of the genomic segments with high affinity , it limits the access of the RNA to host nucleases and helps to render viral replication a closed process within the cytoplasm. It also acts as a peripheral membrane protein, as does the L protein , an activity that could play a role in its presumed, but not yet demonstrated function as matrix . Until recently, it had not been appreciated that Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences . N is also reported to interact with actin microfilaments, and the SUMO-1 protein . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: encoded protein in comparison to native mRNAs . N protein has been increasingly linked to viral replication and translation, sometimes in previously unanticipated ways. It is among a growing family of diverse viral proteins that can serve as a nonspecific -RNA chaperone\u2016, an activity that should facilitate the L polymerase's access to vRNA for transcription and replication, in that it can transiently dissociate misfolded RNA structures . Some of N protein's effects on translation might not immediately be recognized to be adaptive in nature. It can replace the entire EIF4F translational initiation complex, simultaneously presenting the ribosome with a replacement Title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling", "Passage: Text: glycoprotein , and viral RNA-dependent polymerase protein , respectively. Humans become infected by inhaling contaminated aerosols or by coming into contact with rodent excreta, and they develop two severe acute diseases, namely, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome . Hantavirus infection affects up to 100,000 to 200,000 humans annually, with fulminant HFRS cases most represented in China . Chinese HFRS cases, mainly caused by Hantaan virus infection, account for approximately 90% of all global cases, with a mortality rate ranging from 0.1 to 15% . Since there is neither an effective therapeutic nor FDA-licensed vaccine, further", "Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection\nPassage: These viruses comprise over 70 different pathogens, such as Japanese encephalitis virus , Zika virus , dengue virus , West Nile virus , and yellow fever virus . Most flaviviruses are arthropod borne and cause public health problems worldwide . The development and usage of vaccines against some flaviviruses, such as JEV, YFV, and tick-borne encephalitis virus , have decreased the rates of morbidity and mortality from infections caused by these viruses ; however, flavivirus-induced diseases are still pandemic, and few therapies beyond intensive supportive care are currently available. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: These viruses comprise over 70 different pathogens, such as Japanese encephalitis virus , Zika virus , dengue virus , West Nile virus , and yellow fever virus . Most flaviviruses are arthropod borne and cause public health problems worldwide . The development and usage of vaccines against some flaviviruses, such as JEV, YFV, and tick-borne encephalitis virus , have decreased the rates of morbidity and mortality from infections caused by these viruses ; however, flavivirus-induced diseases are still pandemic, and few therapies beyond intensive supportive care are currently available. Title: Identification of Three Antiviral Inhibitors against Japanese Encephalitis Virus from Library of Pharmacologically Active Compounds 1280", "Passage: Japanese encephalitis virus , a member of the genus Flavivirus in the family Flaviviridae, is a mosquito-transmitted and zoonotic pathogen that causes 50,000 cases and 10,000 deaths per year . There are .70 arboviruses in the genus Flavivirus including JEV, dengue virus , West Nile virus , and yellow fever virus . JEV can cause severe central nervous disorders such as poliomyelitis-like paralysis, aseptic meningitis, and encephalitis in humans. The fatality rate caused by JEV is 10-50% and half of the survivors have severe neurological sequelae, including persistent motor defects and severe cognitive and language impairments . The geographic range Title: Non-Hemagglutinating Flaviviruses: Molecular Mechanisms for the Emergence of New Strains via Adaptation to European Ticks", "Passage: Tick-borne encephalitis virus causes up to 14,000 human cases of tick-borne encephalitis across Eurasia annually . TBE outbreaks are now registered in about 30 European countries with a recorded morbidity increase of about 400% during the past 30 years . TBEV is a member of the tick-borne flavivirus group that, together with mosquito-borne and no-known vector virus groups comprise the genus Flavivirus within the family Flaviviridae. Human pathogens within the genus Flavivirus include Japanese encephalitis virus, Dengue virus and Yellow fever virus that cause annual epidemics of fever, encephalitis and hemorrhagic fever in the tropics and some sub-tropical regions .", "Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats\nPassage: Of the more than four thousand known mammalian species, 50% are rodents and 25% are bats. This rich species diversity, plus other ecological traits , suggests that surveillance efforts focused on rodents and bats could offer high value. Rodents are typically small and can be trapped in large numbers for surveillance, and they are easier to handle and less expensive to keep in laboratory settings than large animals. The ability to study viral infections in animal hosts under controlled laboratory conditions is central to understanding virus-host ecology at molecular and organismal levels, including the duration and severity of infection, immune Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats", "Passage: Of the more than four thousand known mammalian species, ~50% are rodents and ~25% are bats. This rich species diversity, plus other ecological traits , suggests that surveillance efforts focused on rodents and bats could offer high value. Rodents are typically small and can be trapped in large numbers for surveillance, and they are easier to handle and less expensive to keep in laboratory settings than large animals. The ability to study viral infections in animal hosts under controlled laboratory conditions is central to understanding virus-host ecology at molecular and organismal levels, including the duration and severity of infection, immune Title: High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress", "Passage: Bats are the only mammal that have mastered true flight, and consequently, they must endure elevated body temperatures throughout flight. Additionally, most have longer lifespans than terrestrial mammals of similar body sizes, despite their high metabolic rate and its predicted consequences on oxidative metabolism. As such, they have one of the greatest disparities between body mass and longevity . Their longevity has been attributed, at least in part, to enhanced oxidative stress resistance and protein homeostasis Yin et al. 2016) . The body temperature of bats raises drastically during flight , and there is an excessive increase in metabolic rate Title: Temporal Anomalies in Immunological Gene Expression in a Time Series of Wild Mice: Signature of an Epidemic?", "Passage: could occur because animals in better starting condition might be more likely to survive infection, thus raising their representation in infected classes by differential mortality. The immunoregulatory influence of macroparasites might also be important in this context: dampening potentially lethal immunopathogenic inflammatory responses. A further possibility is that individual mice respond to infection by adjusting life history traits in a way that produces an overcompensatory response in body condition. For example, A. sylvaticus infected with cowpox virus in summer may show positive effects on survival due to a diversion of resources from reproduction .", "Title: CDC Summary 21 MAR 2020,\nPassage: If you have been in China or another affected area or have been exposed to someone sick with COVID-19 in the last 14 days, you will face some limitations on your movement and activity. Please follow instructions during this time. Your cooperation is integral to the ongoing public health response to try to slow spread of this virus. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: have been mild . Title: Estimating the number of infections and the impact of non-\nPassage: In China, strict movement restrictions and other measures including case isolation and quarantine Title: Quantifying social distancing arising from pandemic influenza", "Passage: We define period A as beginning from the time when the first cases were identified . During this period, extensive infection control measures were imposed, including: closing theatres and public places of entertainment; compulsory wearing of masks on all public transport and in public places; closure of schools; prohibition of race meetings and church services; and removal of patients to hospital and strict quarantine of contact for a complete list). As the incidence remained low in comparison with severe epidemics reported from elsewhere around the world, authorities deemed that the threat had passed and most measures were lifted on 1", "Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses\nPassage: mice have two other IFITM genes: IFITM6 and IFITM7. . These proteins inhibit viral membrane fusion, thus resulting in cellular protection from a diverse range of infections. An early observation of IFITM proteins controlling viral infection was reported in 1996 , where overexpression of IFITM1 was shown to inhibit VSV replication, although less potently than the IFN-induced protein MxA . This study is the first description of the antiviral activity of an IFITM protein. Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses", "Passage: All IFITM proteins have been shown to restrict cell entry of many viruses . However, IFITM3 is the most potent IFITM family member in restricting viral replication in cell culture . IFITM3 inhibits a VSV entry step following endocytosis, but at or before the point of primary transcription of incoming viral genomes . Both the N-terminal 21 amino acid residues and C-terminal transmembrane region of IFITM3 are required for its antiviral function. In addition, IFITM3 has been shown to inhibit an early stage of the RABV replication cycle by targeting entry mediated by the viral glycoprotein . Title: Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane\u2010Associated Protein IFITM3 and Modified Variants", "Passage: Interferon-induced transmembrane protein 3 is a1 33 amino acid membrane-associated protein that inhibits the replication of pathogenic viruses.This protein was first named fragilis and reported by Saitou and co-workers in 2002, but interest surged when its antiviral properties came to light during the 2009 H1N1 influenza pandemic. Everitt and co-workers reported that patients lacking full IFITM3 were more quickly and severely infected, leading to adramatic increase in mortality.S ubsequent studies have shown that IFITM3 exhibits antiviral activity against al arge number of viruses, including West Nile virus, Dengue virus, Filoviruses , SARS Coronavirus, Rift Va lley fever virus, HIV-1 and, Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses", "Passage: The IFN-inducible transmembrane genes are enhanced by cell treatment with IFNs since they contain the ISREs in their promoter. IFITM proteins belong to the CD225 protein superfamily, which can be found in nearly every domain of life, ranging from bacteria to invertebrates to primates. In humans, there are at least four functional members of IFITM proteins: IFITM1, IFITM2 and IFITM3, previously named 9-27, 1-8D and 1-8U, respectively, are expressed in a variety of tissues; IFITM5 is limited to the bone. IFIM4P is a pseudogene ). Mouse IFITM1, IFITM2, IFITM3 and IFITM5 genes are orthologues to their human counterparts. In addition,", "Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients\nPassage: binding of the incoming nucleotide; nonnucleoside NS5B polymerase inhibitors interact with either the thumb 1, thumb 2, palm 1, or palm 2 domain of NS5B and inhibit polymerase activity by allosteric mechanisms . However, the extreme mutation and high replication rates of HCV, together with the immune system pressure, lead to a remarkable genetic variability that can compromise the high response rates to DAAs due to the preexistence of resistanceassociated substitutions . Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: the binding of the incoming nucleotide; nonnucleoside NS5B polymerase inhibitors interact with either the thumb 1, thumb 2, palm 1, or palm 2 domain of NS5B and inhibit polymerase activity by allosteric mechanisms . However, the extreme mutation and high replication rates of HCV, together with the immune system pressure, lead to a remarkable genetic variability that can compromise the high response rates to DAAs due to the preexistence of resistanceassociated substitutions . Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: The primary mechanism to explain the antiviral effect of nucleoside analogs is based on their direct action on viral polymerization. Nucleoside analogs are transported into the cells and phosphorylated by the consecutive action of viral or cellular kinases, eventually generating nucleotide triphosphates. Mature nucleotide analogs, which are similar to physiological nucleotides, can directly incorporate into the growing viral genome during polymerization, resulting in the termination of chain reaction or the accumulation of mutations . Alternatively, nucleotide analogs can bind to the nucleotide-binding region on viral polymerases and block the entry of incoming natural nucleotides. The other mechanism is based on Title: Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases\nPassage: efforts support the hypothesis that the mechanism of action of this compound class establishes a strong barrier against rapid viral escape from inhibition.", "Title: Assessment of Temporary Community-Based Health Care Facilities During Arbaeenia Mass Gathering at Karbala, Iraq: Cross-Sectional Survey Study\nPassage: Any new systems should be in place for a sufficient length of time prior to the MG to allow baselines to be determined, to assess the effectiveness of collection, analysis and interpretation of the data, and to allow the persons involved to become comfortable with the system. Key questions that must be asked by host countries in establishing pre-MG surveillance are as follows: Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust", "Passage: Data are produced in response to some perceived need, which must be articulated in questions that determine what data are collected, and in analyses determining how they will be understood. Those choosing the questions may or may not be the end users of the data; but their interests and aims will certainly influence the utility of the data to all potential users. Title: Innovations in research ethics governance in humanitarian settings", "Passage: a. What information ought to be provided? This will usually include the following elements: the reasons for doing research, details about who is doing the research, why the potential participant is being asked to be involved, details about what any intervention might involve and any on-going commitments of participation, details about anticipated risks and benefits, the fact that participants are free to refuse or withdraw, that any findings will be communicated back to the participants etc. The information given should be proportionate to any risks, but this does not mean that the higher the risk, the more information ought to Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust", "Passage: In middle-and higher-income countries, subnational data collection is part of the routine function of health systems funded out of routine government spending. In low-income countries they may be externally funded through international survey programmes such as the Demographic and Health Surveys or the Multi-Indicator Cluster Surveys. These surveys, like routine data collection, are generally carried out by government staff. This creates an institutional imperative to use the data: they are locally owned, produced by colleagues who may be directly involved in communicating results and who can help explain anomalies in the data and their meaning in the specific local situation", "Title: Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease\nPassage: In human cells 300 copies of the rRNA genes are arranged in repeated arrays located in nucleolar organizer regions on the short arms of the acrocentric chromosomes . Pol I transcribes rDNA to produce the 47S rRNA, which is the precursor of the mature 28S, 5.8S, and 18S rRNAs. Together with the 5S rRNA transcribed by Pol III in the nucleoplasm, these rRNAs form the nucleic acid backbone of the ribosome. The other major components of the ribosome are the~78 ribosomal proteins , whose genes are transcribed by Pol II, and are assembled with the rRNAs to form functional ribosomes Title: Nucleolus: the fascinating nuclear body", "Passage: The nucleolus is the ribosome factory of the cell. In the nucleolus rDNAs are transcribed, the 47S precursor ribosomal RNAs are cleaved, processed and assembled with the 80 ribosomal proteins and the 5S RNA to form the 40S and 60S ribosomal subunits . This complex series of maturation and processing events, presently better characterized in yeast than in higher eukaryotes is under the control of about 150 small nucleolar RNAs and 2 large RNP complexes: the small subunit processome containing the U3 snoR-NAs and 40 proteins or Utps required for the 40S ribosomal subunit, and the large subunit processome required Title: Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease", "Passage: The nucleolus is the subnuclear site of ribosome biogenesis and its formation around active NORs requires ongoing rDNA transcription. The structure of nucleoli is highly dynamic and is tightly coordinated with cell cycle progression. Nucleoli disassemble at the onset of mitosis coinciding with inactivation of Pol I transcription and reassemble during telophase as rDNA transcription is reinitiated. The rate of rRNA gene transcription reaches a maximum in S-and G2 phases, is halted at the onset of mitosis and slowly reactivated as cell enter G1 . Cell cycle mediated regulation of rDNA transcription is facilitated by post-translational modifications of components of Title: Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease\nPassage: nucleolar ribonucleoproteins necessary for the first steps of rRNA processing, whereas the late steps of rRNA processing and assembly of the small and large ribosome subunits take place in the GCs .", "Title: Estimating the number of infections and the impact of non-\nPassage: after-italian-lockdown . Title: Estimating the number of infections and the impact of non-\nPassage: https://edition.cnn.com/2020/03/08/europe/italy-coronavirus-lockdown-europe-intl/index.html Title: Estimating the number of infections and the impact of non-\nPassage: 39. CNN. Italy prohibits travel and cancels all public events in its northern region. CNN Title: Estimating the number of infections and the impact of non-\nPassage: Italy measures and quarantine if tested positive.41 9/3/2020", "Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model\nPassage: After emerging in southern China in the mid-1990s, the highly pathogenic avian influenza H5N1 virus spread across east and Southeast Asia, causing unprecedented epidemics in 2003-2004 . As of 24 September 2009, the virus has caused 442 human cases, with 262 deaths worldwide 1 . Controlling the spread of H5N1 disease in poultry may contribute to the reduction of risk for humans by preventing the emergence of a viral form with efficient human-to-human transmission capable of triggering a global pandemic . Determining the factors involved in the spread of H5N1 in poultry and producing risk maps are critical to disease Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: control as they would enable control measures to be targeted and surveillance in ''high-risk'' areas to be strengthened. The HPAI H5N1 virus is now well established in the poultry population in Asia, where the virus has been able to maintain itself and spread as well as periodically re-emerge. The main pathways that have been identified for the spread of H5N1 are the migration and trade of wild birds and the transport of poultry and poultry products . However, the respective roles of these pathways at the global or national scale are still unclear . The persistence of HPAI H5N1 virus Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: The H5N1 virus may now be well established in different Southeast Asian countries. Despite the implementation of control measures, it is probable that these countries will continue to face new outbreaks in poultry. The conditions under which the virus maintains itself in the environment are not well known. It is difficult to prevent virus re-emergence in possible local persistence spots, or the periodic reintroduction of the virus . Controlling the disease within the poultry population is a critical issue for both the public health and agricultural economic systems. The restructuring of poultry production from open-housed to closed systems has started Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: in Thailand but the process will take time and considerable cooperative effort. Therefore, to limit the number and size of future outbreaks in the poultry population, the focus of efforts should be on controlling the movement of both live poultry and avian products.", "Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication\nPassage: Text: Feline Infectious Peritonitis Virus is an enveloped virus with a nonsegmented, positive sense, single-stranded RNA genome. FIPV is grouped as feline coronavirus , under the family Coronaviridae. FCoV is divided into two biotypes, namely, Feline Enteric Coronavirus , a ubiquitous enteric biotype of FCoV, and FIPV, a virulent biotype of FCoV . The relationship between these two biotypes still remains unclear. Two hypotheses have been proposed, internal mutation theory and circulating high virulent-low virulent theory. Internal mutation theory stated that the development of FIP is due to the exposure of cat to variants of FCoV which have been mutated Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication", "Passage: Study has shown that about 40-80% of cats are detected with FECV shedding in their faeces . About 12% of these FECV-positive cats have developed immune-mediated fatal FIP disease . The prevalence of FIP among felines is due to continual cycles of infection and reinfection of FECV and indiscernible clinical symptoms of infected cats with FECV at an early stage before the progressive development of FIPV. Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950953/ Title: In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication\nPassage: ORF1a/1b and 14048-14061", "Title: Nanorobot Hardware Architecture for Medical Defense\nPassage: Time for incubation of pandemic syndromes may vary from one contagious plague to another, and first symptoms can be predicted given clinical information and previous historic occurrences, using statistical models. The size of an outbreak is directly correlated and influenced by the delay for recognition about the contaminated area. The incubation period of disease is the time from exposure to the infectious agent to the onset of disease, and depending on the infection dose of influenza, it can vary about 2 to 5 days . For influenza, the contamination can happens through inhalation, ingestion, or direct contact through hand shaking Title: Introducing the Outbreak Threshold in Epidemiology", "Passage: as the fact that the incubation period is around 5 days, by which point it had easily caused more secondary cases. However, in subsequent outbreaks super-spreaders might not be infected early on, allowing more time to contain the spread. Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Astrovirus, rotavirus, and caliciviruses are important causes of healthcare associated infections and institutional outbreaks . The incubation period is important for accurate surveillance for healthcare associated infections and implementation of effective outbreak control measures . The incubation period is frequently used to determine the infecting exposure in foodborne outbreaks and can assist in diagnosis when laboratory resources are unavailable. Kaplan's criteria were developed and are frequently employed to determine whether an outbreak was caused by norovirus; the incubation period is one of the key elements of these criteria. Other applications of a precisely described incubation period include predictive models that Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Despite its importance, the incubation periods of enteric viruses are not well characterized in the medical literature. Statements of the incubation period tend to be a single number ) or a poorly defined range ). It is difficult to translate these statements of incubation period into the realities of prevention and control. The single number estimate could represent the mean, median, upper limit, or some other measure of the incubation period. The range could represent an exhaustive range of all observations, or some unspecified quantile . Furthermore, the strength of the evidence behind these estimates is often unclear. Statements of", "Title: Markers of exacerbation severity in chronic obstructive pulmonary disease\nPassage: Another important consideration for future clinical trials is the assessment of treatment effect based on predictions of exacerbation frequency and intensity. In other words, the collection of data such as the rate of onset and resolution of an exacerbation from longitudinal studies could be used to determine probabilities of second, third, fourth, etc., exacerbation events in individual patients . The alteration of such probabilities with an experimental treatment could be a more sensitive and reliable approach for assessing treatment effect in clinical trials than recording daily changes in symptoms or medical management. Title: Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children", "Passage: 1b. Visits were defined as an exacerbation event if the participant was treated by a physician with systemic corticosteroids in the 10 d following onset of cold symptoms; otherwise, they were defined as a cold without exacerbation . Criteria for the initiation of systemic corticosteroids were as previously specified in Inner-City Asthma Consortium trials 4 . Participants were treated with systemic corticosteroids if albuterol was needed by inhaler or nebulization for more than six individual treatments over 24 h; moderate-to-severe wheeze, cough, shortness of breath, and/or chest tightness or pain occurred for at least 5 of the preceding 7 d; Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Finally, the compatibility between the studies of COPD exacerbation that we analysed may have been limited by substantial variations in the time and location of studies. Exacerbations are more likely in summer but many studies failed to report the time of year or the time period for study implementation. Thus, seasonal effects, combined with the low incidence of exacerbations per patient, could represent an inherent bias. In addition, different institutions probably had different standards with respect to diagnosis and management of COPD exacerbations when these studies were performed. Such variations may also explain any observed inconsistencies in our findings. However, Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: well as suggested markers of the severity of the exacerbation at baseline conditions, i.e., immediately prior to, or during the exacerbation event but before the time in which the intervention of interest was investigated . Whenever such variables were measured in stable conditions, we also abstracted this information. For each study, we noted the type of definition used to define an exacerbation such as symptom-or event-based as well as the research question asked, the experimental design used, any sponsorship, and the presence or absence of data from individual study patients. Data was then further organized according to sample size and", "Title: Assay Challenges for Emerging Infectious Diseases: The Zika Experience\nPassage: If assay performance consistency and quality is not demonstrated, the validity of clinical study results may be questioned. Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs\nPassage: per experiment, two plates for detecting inhibition of EBOV, and one mock plate for determining drug cytotoxicity. After 1 h of predilution and transport to the BSL4 laboratory, 50 \u03bcl of virus at the desired MOI was added to cells. At 48, 72 or 96 hpi, assay plates were fixed at final concentration of 10% NBF for 24 h before transferring to a BSL-2 lab for staining. Infected cells were detected as described above. To further confirm the accuracy of assays with high background, chemiluminescence assay was performed afterwards. Title: Cas12a-Based On-Site and Rapid Nucleic Acid Detection of African Swine Fever", "Passage: The gray values of the test bands in the CORDS assays were measured and recorded. A positive result was recorded when the concentration of the dsDNA target was 1 \u00d7 10 \u221215 M, which further confirmed the assay's sensitivity . The 13 NA samples from typical porcine viruses were tested with this assay, all of which were negative. Thus, no cross-reactions were observed . Title: Simultaneous detection of eleven sexually transmitted agents using multiplexed PCR coupled with MALDI-TOF analysis", "Passage: For further analysis of the 40 specimens that yielded discrepant results with the developed STI-MS assay and the confirmatory tests, ultrasensitive digital PCR was performed. Among these 40 STI-MS-positive and confirmatory test-negative samples, 31 were confirmed as positive by a digital PCR assay, whereas 9 remained unverified after the resolution of the discordant results, including 4 single organism samples and 5 multiple agent combination samples . The results of the confirmatory tests and arbitration testing revealed that all retested specimens that were verified as positive by either of the tests were indeed accurate positive, irrespective of their classification as negative", "Title: Chinese journals: a guide for epidemiologists\nPassage: results. However, subsequent studies found little evidence supporting this assertion. Pham et al. found that language bias led to an under-estimation of the protective effect of intervention in RCTs in complementary and alternative medicine systematic reviews but not in that of conventional medicine . Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: We observed generally low adherence to interventions. More than one in four household contacts in the face mask group did not wear a surgical mask at all during the follow-up period. Adherence to the face mask intervention was higher in the index subjects, likely due to their intention to reduce the probability of infecting other household members and possibly because of the recent memory of SARS in 2003, during which the majority of the general public reported that they wore face masks in public, and most engaged in numerous protective practices . However more than one in four index cases Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: In terms of adherence, 45% of index subjects in the face mask arm reported wearing a mask often or always during the follow-up period, compared to 30% and 28% in the control and hand hygiene arms, respectively. The higher reported compliance in index subjects in the face mask group compared to household contacts was validated when at the final home visits the index subjects had used a median of 12 masks whereas household contacts had only used a median of 6 ; these include the mask worn and then disposed of by each individual as part of the demonstration and Title: The Trojan Chicken Study, Minnesota", "Passage: Some of our study findings were unanticipated. We expected contamination proportions to vary by age, gender, and role because we expected these factors to affect the amount of contact with birds and handwashing behavior. However the rates did not vary by these variables. This finding could be due to the study's limited power to detect such differences. If the differences between those exposed and those unexposed were statistically significant , they might be consistent with studies that suggest that animal handlers practice better hygiene compared to nonhandlers in the same environment. Alternatively, animal handlers may engage in other behavior that", "Title: Antibody Engineering for Pursuing a Healthier Future\nPassage: Filamentous bacteriophages used in phage display techniques are viruses that belong to the Inoviridae family. There are fewer of these filamentous phages in this genus compared with tailed phages. Inovirus virions are 7 mm in diameter, contain circular DNA enclosed in a protein capsid, and infect both Gram negative and positive bacteria. They do not lyse host cells, instead, they are packed and extrude at the surface . Title: Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines", "Passage: Text: Filamentous bacterial viruses are a group of thread-like viruses containing single-stranded DNA genomes. Collectively, they constitute the genus Inovirus in the family Inoviridae, the terms deriving from the Greek word \u038a\u03bd\u03b1 for filament , and they are commonly called filamentous bacteriophages. There are over 50 different known individual species of filamentous viruses; the majority of them capable of infecting Gram-negative bacteria. The complex interaction between filamentous phages and their bacterial hosts is specified by receptor organelles that are usually encoded by transmissible plasmids . One of the most intriguing features of inoviruses is that they are assembled at the Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Long before the identification of filamentous phage, other types of bacteriophage were already being used for antibacterial therapy in the former Soviet Union and Eastern Europe . The filamentous phage, with its nonlytic life cycle, has less obvious clinical uses, despite the fact that the host specificity of Inovirus and Plectrovirus includes many pathogens of medical importance, including Salmonella, E. coli, Shigella, Pseudomonas, Clostridium, and Mycoplasma species. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Long before the identification of filamentous phage, other types of bacteriophage were already being used for antibacterial therapy in the former Soviet Union and Eastern Europe . The filamentous phage, with its nonlytic life cycle, has less obvious clinical uses, despite the fact that the host specificity of Inovirus and Plectrovirus includes many pathogens of medical importance, including Salmonella, E. coli, Shigella, Pseudomonas, Clostridium, and Mycoplasma species.", "Title: Clinical characteristics and outcomes during a severe influenza season in China during 2017\u20132018\nPassage: in the 14-59 and > 60 groups. Title: Clinical features and risk factors for severe and critical pregnant women with 2009 pandemic H1N1 influenza infection in China", "Passage: All patients who were admitted to hospitals with confirmed 2009 pH1N1 influenza from Sep. 1 to Dec. 31, 2009 from 27 Chinese provinces were screened if they fulfilled the diagnostic criteria for severe or critical cases. A confirmed case was a person whose pH1N1 virus infection was verified by real-time reverse-transcriptase polymerase chain reaction with or without the presentation of other clinical symptoms. Patients were excluded if they had been treated as outpatients or in emergency rooms or duration of hospitalization < 24 h, or if they had incomplete records of clinical outcomes. Severe and critical cases were defined according Title: Clinical characteristics and outcomes during a severe influenza season in China during 2017\u20132018\nPassage: underlying diseases . A critical case met at least one of the following criteria on admission: respiratory failure; Title: Clinical features and risk factors for severe and critical pregnant women with 2009 pandemic H1N1 influenza infection in China", "Passage: patients , 54% avoided intubation and had excellent outcomes .", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: 2 days . The mean duration from the first positive CXR to bilaterally multilobar lung infiltrates was 4.8 days . Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: 2 days . The mean duration from the first positive CXR to bilaterally multilobar lung infiltrates was 4.8 days . Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 \u00d7 10 copies in three patients and was Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: 1 \u00d7 10 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The", "Title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985\u20132008\nPassage: Available estimates of the burden of childhood pneumonia in China vary widely, and pneumonia accounts for an estimated 17% of all child deaths in China and 67% of all childhood pneumonia deaths in the Western Pacific region . Title: Pneumonia in Bhutanese children: what we know, and what we need to know", "Passage: In 2015, pneumonia was ranked as the single biggest killer of post-neonatal children worldwide. With an estimated 15\u00b75% attributable fraction of all deaths in children under 5 years of age, pneumonia is believed to be responsible for the deaths of around 900,000 children every year . The main burden remains disproportionately concentrated in low-and middle-income countries in Southeast Asia and sub-Saharan Africa, where pneumonia is one of the most frequent triggers of health facility consultation, and one of the most common causes of hospitalization, representing a huge load for the overburdened and fragile health care systems . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Text: Pneumonia has been the leading cause of death in children younger than 5 years for decades. Although there have been substantial decreases in overall child mortality and in pneumonia-specific mortality, pneumonia remains the major single cause of death in children outside the neonatal period, causing approximately 900,000 of the estimated 6.3 million child deaths in 2013 . Substantial advances have occurred in the understanding of risk factors and etiology of pneumonia, in development of standardized case definitions, and in prevention with the production of improved vaccines and in treatment. Such advances have led to changes in the epidemiology, etiology Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: . Pneumonia deaths decreased from 1.8 million in 2000 to 900,000 in 2013 . These data do not reflect the full impact of increasingly widespread use of pneumococcal conjugate vaccine in low-and middle-income countries because the incidence of pneumonia and number of deaths are likely to decrease still further as a result of this widespread intervention .", "Title: Exploration of diarrhoea seasonality and its drivers in China\nPassage: at higher latitudes were greater than lower latitudes. Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: also different from the studies conducted in northern or central cities of China, in which the seasonality of most viruses presented in autumn-winter and/or winter-spring. 15, 30 The winter-spring seasonality was also observed in Guangzhou, a city about 150 kilometers north of Shenzhen. 28 Different seasonal onset and duration were observed in various studies conducted in tropical regions. In these studies, ambient temperature, humidity and rainfall were widely used to explain these differences in seasonality, but inconsistent results were observed. 9, 46, 47 Although most studies demonstrated that the seasonality of viral respiratory infections was correlated with increased rainfall, effects Title: Exploration of diarrhoea seasonality and its drivers in China", "Passage: In conclusion, our study unfolds the striking difference in diarrhoea seasonality between children ,5 years and persons .55 years. The distinct geographic patterns of diarrhoea, which may be impacted by climatic factors, were also unveiled. Future research should focus more on elucidating the impact of social-environmental changes on diarrhoea in different epidemiological zones and mechanisms why diarrhoea seasonality differs greatly across different age groups. Our work has practical implications for the development of early warning systems targeting different population in different regions. Title: Seasonal distribution of active systemic lupus erythematosus and its correlation with meteorological factors\nPassage: SLE was significantly higher in winter than in spring , summer and autumn . There was no statistical significance in relative ratios of patients with active SLE between spring, summer and autumn .", "Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak\nPassage: detected both the autumn-winter wave of the 2009-2010 swine flu pandemic and the seasonal flu epidemic of 2011. Outbreak detection was successful for both the weekly data and the daily data, even though the daily data appear quite noisy to the eye. Title: The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile", "Passage: A/H1N1 influenza is sensitive to temperature and humidity levels . Moreover, the timing and intensity of the 2009 A/ H1N1 pandemic waves varied substantially across regions of the world , suggesting a potential link with local meteorological conditions. Further, the occurrence of recrudescent waves of pandemic activity in the South-Eastern US in winter 2010 was associated with low humidity levels . Title: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak\nPassage: to the smoothing, we performed a simple analysis of the seasonality of fever rates, as discussed in the second supplemental appendix . Although the results were not conclusive, we found no evidence of seasonality that was strong enough to warrant consideration in the analysis of fever rates. Title: Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity", "Passage: FLUA and FLUB were detected in few samples; however, these samples were collected during autumn and winter, agreeing to previous studies that showed Inlfuenza outbreaks occurring between late summer and early winter .", "Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys\nPassage: The second survey was conducted in May 2009 when the WHO pandemic influenza alert level assigned to H1N1 influenza was phase 5. Phase 5 signifies human to human spread of the virus into at least two countries within one WHO region. Although most countries are not affected at this stage, the declaration of phase 5 is a strong signal that a pandemic is imminent and that the time to finalise the organisation, communication, and implementation of the planned mitigation measures is short. 1 During this phase 5 period, we repeated our questionnaires in the three specialties in one hospital. All Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys", "Passage: In 2005 the World Health Organization recommended its member states to revise or construct a preparedness plan for pandemic influenza. The WHO also set up a system of influenza pandemic alert levels. Phases 1-3 include capacity development and response planning, while phases 4-6 signify the need for response and mitigation efforts. 1 By August 2008, 47 countries had prepared such a plan. 2 The recent spread of infection with a novel influenza A virus of swine origin has prompted governments to review and carry out their pandemic responses, including vaccination strategies. Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys\nPassage: virus has gained the level of transmissibility among humans necessary to cause a pandemic. Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys", "Passage: The first survey was conducted from January 2009 to March 2009. The WHO influenza pandemic alert level assigned to H5N1 during that period was phase 3. Phase 3 signifies an animal or human-animal influenza reassortant virus that has caused sporadic cases or small clusters of disease in people but has not resulted in human to human transmission sufficient to sustain community level outbreaks. Limited human to human transmission may occur under some circumstances, such as when there is close contact between an infected person and an unprotected carer. However, limited transmission under such restricted circumstances does not indicate that the", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: the surface-exposed N-terminal \u223c12 residues of the pVIII monomer lattice ; the N-terminal N1 and N2 domains of pIII ; and bacterial lipopolysaccharide embedded in the phage coat . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization . Primary antibody responses against the phage appear to be composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: the surface-exposed N-terminal \u223c12 residues of the pVIII monomer lattice ; the N-terminal N1 and N2 domains of pIII ; and bacterial lipopolysaccharide embedded in the phage coat . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization . Primary antibody responses against the phage appear to be composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection", "Passage: cells or the primary IgG plasmablast responses and a p-value of <0.0001 against the IgM populations. Notably, besides patient EM, each individual set of VH genes averaged significantly more mutations than the IgG memory and GC or the primary responses . Each point represents one individual donor and is averaged from 25-75 sequences, except for the primary response to anthrax from which only 10 VH genes could be cloned from single cells because of the highly limited response. Mutations accumulated per individual sequence are depicted in Fig. S3 . Detailed sequence characteristics are provided in Tables S1-S3. The naive, IgG Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: antibody responses are composed primarily of IgG1 and IgG2b isotypes, with a lesser contribution of IgG2c and IgG3 isotypes . Deletion of the surface-exposed N1 and N2 domains of pIII produces a truncated form of this protein that does not elicit antibodies, but also results in a non-infective phage particle with lower overall immunogenicity .", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: on six or more of the ten criteria. Based on the weak reviews, 10.5% did not have a clearly focused question, 46.5% did not use appropriate inclusion criteria, 87.7% did not have a comprehensive search strategy, 34% did not cover an adequate number of years, 48% did not describe the level of evidence in the primary studies, 96.6% did not assess the methodological Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: of homogeneity or assessment of similarity of results across studies was conducted and reported; 9) appropriate weighting of primary studies was conducted; and 10) the author's interpretation of the results were supported by the data . Each criterion is equally weighted and a final methodological score is tallied out of 10. Reviews with an overall rating of eight or more are considered strong, five to seven, moderate, and below four are considered to be weak in methodological quality. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: In addition there were 68 sub-topics with fewer than five reviews available, such as lung cancer, testicular cancer, food service inspection, fetal alcohol syndrome, sexual assault, and social justice. The full list of subtopics with fewer than five reviews is included in Table 5 . Most of the sub-topics with fewer than five reviews were within the registered users and visitors' topic areas of interest. Topic areas which were of interest to both registered user and visitors only had a small proportion of sub-topics with less than five reviews available . Whereas the communicable disease/infection topic area, which ranked tenth Title: Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review", "Passage: Concerning NRSI combined, 52 meta-analyses included only cohort studies and 5 only prospective cohort studies; 46 meta-analyses combined cohort and case-control studies, and 23 included all types of NRSI. The other 67 meta-analyses included \"observational studies\" , \"prospective and retrospective studies\" , and only \"retrospective studies\" .", "Title: Identification of COVID-19 Can be Quicker through Artificial Intelligence framework using a Mobile Phone-Based Survey in the Populations when Cities/Towns Are Under Quarantine\nPassage: have any mild symptoms and signs. Title: Identification of COVID-19 Can be Quicker through Artificial Intelligence framework using a Mobile Phone-Based Survey in the Populations when Cities/Towns Are Under Quarantine\nPassage: with the virus. The identification of the high-risk cases can then be quarantined earlier, thus decreasing the chance of spread. Table 1 is inserted here. Title: Identification of COVID-19 Can be Quicker through Artificial Intelligence framework using a Mobile Phone-Based Survey in the Populations when Cities/Towns Are Under Quarantine", "Passage: do doorto-door assessments and even testing for the virus. This generates alert for mobile health check recommendation for 2019-nCoV . If a respondent does not have an immediate risk of having symptoms or signs related to the viral infection, then the AI-based health alert will be sent to the respondent to notify them that there is no current risk of COVID-2019. Figure 1 summarizes the outcomes of data collection and identification of possible cases. The data recorded in step 5 of the algorithm using signs and symptoms will be collected prior to both the groups who have received alerts HCRC Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: person. In addition, some mildly ill or potentially even asymptomatic patients may have a higher chance of spreading the disease to others as they may be less likely to seek medical care. 34 The possibility that patients may be infectious prior to symptom onset further compounds the difficulty of containing the virus and effectively preventing transmission.", "Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: Nasal swabs were collected in the mid-nasal region for influenza virus detection, which may have lowered the sensitivity of pertussis detection. In a field site, the acceptability of an additional nasopharyngeal swab would likely have increased the participant refusal rate. This would have decreased the generalizability of our results to the entire population. Although nasopharyngeal swabs or nasopharyngeal aspirates are the recommended specimen collection method , the nasopharyngeal region was established as the collection area of choice when the diagnostic measure was culture, which has low sensitivity. Recent data demonstrated the comparability of using mid-nasal versus nasopharyngeal swabs in PCR Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: swab is an attractive alternative for pertussis nasal swab collection, and further research is needed to compare this collection site with nasopharyngeal swabs. In the future, this method may enhance population-based surveillance efforts. Title: Detection of Common Respiratory Viruses and Mycoplasma pneumoniae in Patient-Occupied Rooms in Pediatric Wards", "Passage: Object surface sampling was performed within 2 days after the patients had moved into their rooms. The surfaces of the following items were swabbed in each patient's room: nursing call button, bed handrail, television remote control buttons, light switch, bathroom door knobs , and inner ward room door knob. After surface sampling, the swabs were immediately immersed in 2 mL phosphate-buffered saline and stored at \u00c0808C until analysis. Again, 10% of the blank samples were examined to detect the RNA or DNA of the viruses and M pneumoniae. A total of 406 swab samples were collected. Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: swabs were only taken when patients were symptomatic. Previously, virus isolation has been the gold standard for infl uenza detection but RT-PCR is now considered to be more sensitive and specifi c. A previous study by some of the current authors has shown that seroconversion occurs in 80%-90% of serum samples if they are tested a suffi cient time after infection . Nasal swabs are a relatively peripheral type of sample . If viral load is low in the nose, the sample may be insuffi cient as an antigenic stimulus to induce a detectable level of seroconversion in the serum.", "Title: The protective and pathogenic roles of IL-17 in viral infections: friend or foe?\nPassage: An expansive history of evidence has revealed the essential role of the host immune system in preventing viral infections . The initial sensing of an invading virus by pattern recognition receptors of the host innate immune system induces the production of interferons and other proinflammatory cytokines as a part of the early host antiviral response phase. Afterwards, both the activation of cytotoxic T lymphocytes and B-cell production of neutralizing antibodies ultimately mounts an effective and specific antiviral response for optimal viral clearance. However, despite the essential need for viral control and clearance, the intensity of the antiviral immune response must Title: An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation", "Passage: the lymphocyte immune response. Network analysis further suggests that Irf7 may play a regulatory role upstream of interferon transcription. Title: Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections\nPassage: IFN-I were the first cytokines discovered, a little over 50 years ago, based on their direct, potent and broad antiviral activity . More generally, IFN-I are now known to play an essential role in the global orchestration of antiviral immunity, by linking innate and adaptive immunity through multiple immunoregulatory functions . For instance, IFN-I do not only play a crucial role in the control of the replication of many viruses, but they can also promote NK cell or CD8 T cell antiviral cytotoxic activity, either directly or through the licensing of accessory cells such as conventional dendritic cells . In Title: Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections", "Passage: To promote health over disease, antimicrobial immunity must be tightly regulated to allow the mounting of effector responses of sufficient strength and adequate quality for the control of the invading pathogen, but to prevent the development of immunopathology as could result from exacerbated inflammation. This delicate balance can be achieved in part through negative feedback regulatory loops acting at the level of innate immune responses as discussed earlier for pDC activation. Immunoregulatory mechanisms are also in place to finely tune adaptive immune responses, and pDCs have been demonstrated to be able to contribute to this function. In response to EBV", "Title: Testing Modeling Assumptions in the West Africa Ebola Outbreak\nPassage: model. However, we believe that newer data will confirm our initial conclusions. Title: Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning\nPassage: more members. 139 Such model conclusions depend upon underlying assumptions about population susceptibility and transmission in heterogeneous circumstances. For example, using assumptions based on age-specific attack profiles from the 1957 and 1968 pandemics, Patel et al. obtained two very different estimates for the optimal proportional distribution by age group of a limited number of vaccine doses. 140 Title: Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning", "Passage: Spicer and Lawrence modelled influenza in Greater London from 30 years of mortality data. Exposure to successive drift mutants was assumed to reduce the susceptible pool, which was replenished by births and the emergence of antigenically novel strains. 34 In a model for South-East Asia, Ferguson et al. assumed that 27% of rural households would be resistant to a novel strain of influenza as a result of recent contact with related antigens. 10 Other models 11, 35 or progression to disease given acquisition, 36, 37 to depend on age, indirectly incorporating immune protection. Longini et al. explicitly calculated the influence Title: Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning", "Passage: Model assumptions and predictions should be tested against as many real-world observations as possible to test the sensitivity of the model to different contexts. By valid-ating model outputs against multiple data sources, investigators can tease out which of the parameters determining disease spread are more likely to vary between contexts, and which are relatively constant. To encourage such work, and to make relevant data sets more easily accessible, we have developed an on-line publicly searchable archive , which includes rare historical documents from the 1889-1891 and 1918-1919 pandemics giving individual and group level data on influenza morbidity and mortality. By", "Title: Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus\nPassage: We next examined the protein-binding properties of hnRNP A1DC. Since hnRNP A1 has been shown to interact with the N protein, which also participates in MHV RNA synthesis , we \u00aerst determined whether the dominantnegative mutant of hnRNP A1 retained the ability to interact with the N protein in vitro. GST pull-down assay using various truncation mutants of hnRNP A1 showed that the N protein bound the N-terminal domain of hnRNP A1 ; thus, the binding of hnRNP A1DC ] to the N protein was not affected. We next examined the in vivo interaction of the wt and mutant hnRNP Title: Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus", "Passage: of differences were observed for the N protein in these three cell lines. Actin levels in different cell lines remained relatively constant throughout the infection, except that, in DBT-A1 cells, actin was not detected at 16 and 24 h p.i. due to the loss of the dead cells . These results clearly demonstrated that overexpression of the wt hnRNP A1 accelerated viral protein production, whereas expression of the mutant hnRNP A1 delayed it. We also performed immuno\u00afuorescent staining of the N protein at 7 h p.i. to further con\u00aerm the western blot results. As represented by images shown in Figure Title: Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus", "Passage: 4B , there were more DBT-A1 cells stained positive for the N protein than DBT-VEC cells. Very few cells were found to express the N protein in DBT-A1DC cells. The p22 and N proteins appeared as doublets in some of the lanes of Figure 4A , but the results varied from experiment to experiment. The N protein is known to be phosphorylated . Whether p22 is post-translationally modi\u00aeed is not known. Figure 5A ). DBT-A1 cells showed a signi\u00aecantly higher level of uridine incorporation, which peaked at~8 h p.i. DBT-A1DC cells did not show any detectable level of incorporation of Title: Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus", "Passage: GST pull-down assay GST pull-down was performed as described previously . In brief, GST\u00b1hnRNP A1 fusion proteins on glutathione beads were incubated with the in vitro translated, 35 S-labeled N protein in 0.3 ml of GST-binding buffer containing 0.1% NP-40 for 2 h at 4\u00b0C. The beads were washed \u00aeve times with the GST-binding buffer containing 0.3% NP-40. Proteins bound to beads were eluted by boiling in Laemmli buffer for 5 min and separated on a 10% polyacrylamide gel.", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: Researches showed that the R 0 of severe acute respiratory syndrome was about 2.7-3.4 or 2-4 in Hong Kong, China . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 . The transmissibility of the Middle East respiratory syndrome is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 , with the inter-human transmissibility of the disease was about Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1", "Passage: report the value for R 0 from this analysis. The median of the estimates over the 1000 simulated datasets is shown for each scenario along with the interquartile range of estimates obtained. Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: Similar to assumptions in , we defined the value of \u03bb r as 0.25, an arbitrary value for generating synthetic incidence data. Six known values of R 0 are 2.05, 2.58, 3.12 1.51, 1.52 and 1.53, respectively. In Fig 1A, we show that model B with age structure yields a better estimate of R 0 and converges at the true value more quickly in the early phase of the epidemic over non-age-structured model A . Between day 9 and day 15, the estimated R 0 values fluctuate~0.4% around the true value. Between day 0 and day 15, less than 100 Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: 0.6 or 0.9 in Middle East countries . However, MERS had a high transmissibility in the outbreak in the Republic of Korea with the R 0 of 2.5-7.2 . Therefore, the transmissibility of SARS-CoV-2 might be higher than MERS in the Middle East countries, similar to SARS, but lower than MERS transmitted in the Republic of Korea.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: We were also aware that the clinical studies we analysed differed with respect to which comorbidities or identifiable causes for exacerbations were reported. Most patients were elderly and therefore were more likely to be suffering from one or more co-existing diseases such as asthma or cardiovascular disease. Such co-morbidity makes interpretation of our findings more difficult with respect to the true causes of exacerbations. If their aetiology could be determined, then susceptible patients such as those in Level I could be identified and new treatments developed to help prevent their onset and related hospital costs. Title: Th17 profile in COPD exacerbations", "Passage: In general, COPD patients tend to experience frequent exacerbations. Of these, the most frequent are those of infectious origin, with bacteria and viruses being the most prevalent etiological agents, with 50%-70% and 30%, respectively. 37 The clinical manifestations present during exacerbations are a consequence of the action of the virus/bacteria and of the immune response against the pathogen that assembles the host. 38 Bacteria Previously, the lungs were believed to be a sterile area, free of microorganisms. 39 However, recent studies have shown that this is not entirely true and that the lungs contain, depending on the disease or stage Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Chronic obstructive pulmonary disease is a respiratory disease characterized by an airflow limitation and inflammation of the lower airways . As the disease worsens, some patients experience 'exacerbations' of their principal symptoms of dyspnoea, cough and sputum. These exacerbations frequently result in a visit to a general practitioner's office or to a local hospital for treatment. Exacerbations occur in COPD patients at a median of three times a year with half of them being unreported . The heterogeneity of COPD exacerbations make them difficult to define, classify and manage due to their range of symptoms, varied treatment requirements, seasonal occurrence,", "Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo\nPassage: Mapping neuronal connectivity in the central nervous system of even simple organisms is a difficult task. Recombinant viruses engineered to trace synaptic connections and express transgenes promise to enable higher-throughput mapping of connections among neurons than other methods, e.g., serial reconstruction from electron micrographs . The Pseudorabies and Rabies viruses have been the best characterized and most utilized circuit tracing viruses to date . RABV was recently modified by Wickersham and colleagues such that it can travel across only one synapse, allowing for a straightforward definition of monosynaptic connections . This strategy permitted the first unambiguous identification of retrogradely connected Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: rVSV vectors can be used to study the connectivity of neuronal circuitry. In addition to combinations of replication-competent forms of VSV, the replication-incompetent, monosynaptic forms of the virus can be easily combined, without the need to change viruses . This allows a straightforward way to study both the projections into, and out from, a genetically defined cell population. This can be done with the same viral genome, with the only change needed being the glycoprotein, for the selection of the direction of transmission. This flexibility of VSV makes it a powerful, multi-application vector for studying connectivity in the CNS. Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: rVSV vectors can be used to study the connectivity of neuronal circuitry. In addition to combinations of replication-competent forms of VSV, the replication-incompetent, monosynaptic forms of the virus can be easily combined, without the need to change viruses . This allows a straightforward way to study both the projections into, and out from, a genetically defined cell population. This can be done with the same viral genome, with the only change needed being the glycoprotein, for the selection of the direction of transmission. This flexibility of VSV makes it a powerful, multi-application vector for studying connectivity in the CNS. Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: Text: Mapping neuronal connectivity in the central nervous system of even simple organisms is a difficult task. Recombinant viruses engineered to trace synaptic connections and express transgenes promise to enable higher-throughput mapping of connections among neurons than other methods, e.g., serial reconstruction from electron micrographs . The Pseudorabies and Rabies viruses have been the best characterized and most utilized circuit tracing viruses to date . RABV was recently modified by Wickersham and colleagues such that it can travel across only one synapse, allowing for a straightforward definition of monosynaptic connections . This strategy permitted the first unambiguous identification of retrogradely", "Title: Human mobility and the worldwide impact of intentional localized highly pathogenic virus release\nPassage: European countries adhere to a practice that ranks administrative divisions in terms of geocoding for statistical purposes, the so called Nomenclature of Territorial Units for Statistics . Most countries in the European Union are partitioned into three NUTS levels which usually range from states to provinces. The commuting data at this level of resolution is therefore strongly coarse-grained. In order to have a higher geographical resolution of the commuting datasets that could match the resolution scale of our geographical census areas, we looked for smaller local administrative units in Europe. The US or Canada report commuting at the level of Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: However, the self/other divide can be used to facilitate preparing . By considering whether something can be done to assist those more vulnerable, people are more likely to also consider what they can do for themselves. Title: Age groups and spread of influenza: implications for vaccination strategy\nPassage: Finally, as the WHO Strategic Advisory Group of Experts recently made its recommendations for priorities in vaccination for the H1N1 pandemic in terms of the social groups , health groups , and age groups , the model also can be used to divide population into social/health groups. For example, to study vaccine policy for the elderly, we could divide the elderly into those living in households and those living in old age homes, since they mix differently in these two distinct settings. The model is also useful for simulations of the cost-effectiveness of vaccine and other intervention measures, such as Title: Digitizable therapeutics for decentralized mitigation of global pandemics", "Passage: We now consider drug distribution, which divides the population into two separate groups, the treated population, who received the drug Q, and the untreated population who have not yet acquired it. This leads to six distinct states, characterizing each node's population:", "Title: The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care\nPassage: and oncology, MALDI-TOF in the clinical microbiology laboratory, and a variety of mass spectroscopy-based methods in clinical chemistry now allow precise and rapid testing with demonstrated improvements in patient care. It is often thought that when \"laboratory tests\" are done to reach a diagnosis, they are done with a kit or on a machine, but in fact, most are procedures done with the direct involvement of a laboratory professional or physician. Laboratory tests are generally not fully encompassed by a \"test kit\" but often start with the pathologist examining the tissue section, bone marrow aspirate, or gram stain and determining Title: Application of Molecular Diagnostic Techniques for Viral Testing", "Passage: The laboratory must have available detailed SOP, training materials and checklists for each technique performed in the laboratory. Respect to this fact, it would be very important to have a technical expert to provide a reference person in order to apply this methodology in the clinical laboratory. Laboratory-developed tests require that the technical resources to resolve problems related to the assay are available within the laboratory. Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: done by means several techniques . Title: The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care", "Passage: According the Genetic Test Registry, over 50 laboratories in the United States offer testing for FX . Currently, all FX testing is performed as LDPs: No FDA-cleared assay is available. PCR primers and Southern blot reagents are available commercially as analyte-specific reagents or as investigational use only. Clinical laboratories use these commercial reagents, or design primers or probes, combine them internally to develop the assay and establish performance characteristics. The ACMG has published standards and guidelines for clinical laboratories that perform this test. 98 Reference materials to standardize sizing were developed through the Genetic Testing Reference Material program 99 sponsored", "Title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection\nPassage: MHV-3 is a single-stranded, positive-sense RNA virus that belongs to the Coronaviridae family. In inbred laboratory mice, the virus produces strain-dependent disease profiles that depend on the infection route, age, genetic background, and immune status of the host. For example, Balb/c, C57BL/6 and DBA/2 mice develop acute fulminant hepatitis, while C3H mice develop a mild chronic disease and mice of the A strain exhibit no evidence of hepatitis . In contrast to the resistant A strain mice, FH induced by MHV-3 in susceptible mice is characterized by the presence of sinusoidal thrombosis and hepatocellular necrosis . These pathological findings occur Title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection", "Passage: of PD-1deficient liver post-MHV-3 infection, indicating that the PD-1 signal can inhibit IFN-c secretion from NK cells under such condition. Conversely, injection of a the combination of anti-IFNc and anti-TNF-a blocking mAbs was able to successfully inhibit fgl2 mRNA transcription and protein expression, resulting in reduced tissue damage and significantly protecting against MHV-3-mediated mortality in these mice. These results demonstrated that up-regulation of FGL2 in PD-1-deficient mice after MHV-3 infection was controlled, at least partially, by IFN-c and TNF-a. Title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection", "Passage: MHV-3 was kindly provided by Prof. Q. Ning . The virus was plaque-purified and then expanded in murine L2 cells. Virus-containing supernatants were collected and stored at -80uC until use. Mice were intraperitoneally injected with 10 PFU/mouse in a total volume of 200 ml. In some experiments, PD-1-deficient mice were infected with MHV-3 and simultaneously treated with a infection was analyzed by immunohistochemistry. Blue color indicates nuclear DAPI staining. Scale bar = 20 mm. Magnification 6200. NS: not significant different. *p,0.05, ** p,0.01. doi:10.1371/journal.ppat.1001347.g004 combination injection of anti-IFN-c and anti-TNF-a mAbs, tissues were isolated for hematoxylin and eosin staining to Title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection", "Passage: In conclusion, we have determined that PD-1 signaling can limit the immunopathological damage induced by MHV-3 infection in a mouse FH model. Our results suggest that enhancing the PD-1 signal by an immunotherapeutic approach might be a useful treatment for FH.", "Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana\nPassage: Willingness to work during outbreaks and emergencies is deemed a sense of duty even in the face of risk. In this study, less than 50% of HCWs indicated their willingness to work in the event of an EVD outbreak. Additionally, over one third indicated various forms of compensation for themselves or families in case of death or while taking care of an EVD case. This implies that if HCWs are assured or guaranteed that they and or their families would be taken care of in case of death or while taking care of an EVD case, they will willingly work Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: In estimating the sample size for this study, previous data from the hospital indicates that there are approximately 900 HCWs at the two facilities. Assuming a 95% confidence interval and if 70% of these HCWs would come into contact with an EVD suspected case, allowing an error rate of 10%, approximately 87 HCWs would provide a default study power of 80% and an alpha of 5%. With approximately a non-response rate of 15% allowing us to sample 101 HCWs from the two facilities providing emergency services within the Ashanti Region of Ghana. Title: Health workers perceptions and attitude about Ghana\u2019s preparedness towards preventing, containing, and managing Ebola Virus Disease", "Passage: Majority of the respondents indicated their unwillingness to accept posting to EVD treatment centres should there be an outbreak in Ghana, others could offer to help if incentive are provided. A study among health workers in the United States also found that 25.9% of all participants and 43.6% of nurses were unwilling to provide care to Ebola patients with many expressing concerns about personal risk and danger to friends and family members . This study also found that health workers in Ghana are alarmed about higher risk of infection associated with taking care of Ebola patients and possible transmission of Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: The results of this survey showed that more than half HCWs indicated that their facilities were not ready to handle EVD cases. Nearly 92% indicated they were not adequately trained to handle an EVD suspected case and it is not surprising that less than 50% indicated they would willingly attend to a suspected patient. Moreover, nearly a third of HCWs would also want insurance for themselves and their families in case they were infected with EVD.", "Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies\nPassage: system. Recent evidence from genetic characterisation of human patients suggests that haploinsufficiency of KATNAL1 is linked with a number of symptoms including intellectual disability and craniofacial dysmorphologies. 8, 9 It is also notable that a very rare KATNAL1 mutation has been associated with schizophrenia 10 and that Peters syndrome and autism have both been associated with the chromosomal region containing the KATNAL1 locus. 11, 12 Although such association studies strongly suggest that KATNAL1 plays a fundamental role in the central nervous system , additional studies using cellular or animals models are required to understand how the gene may be causative Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: Recent evidence from genetic characterisation of human patients suggests that haploinsufficiency of KATNAL1 is linked with a number of symptoms including intellectual disability and craniofacial dysmorphologies. 8, 9 It is also notable that a very rare KATNAL1 mutation has been associated with schizophrenia 10 and that Peters syndrome and autism have both been associated with the chromosomal region containing the KATNAL1 locus. 11, 12 Although such association studies strongly suggest that KATNAL1 plays a fundamental role in the central nervous system , additional studies using cellular or animals models are required to understand how the gene may be causative for Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: and ciliary function deficits suggesting KATNAL1 plays an essential role in these processes. These findings are the first to our knowledge to conclusively show that mutations in Katnal1 lead to behavioural and neuronal disturbances and provide insight regarding the clinical associations that have been linked to the gene. performed on mouse cohorts that were partially or completely congenic on the C57BL/6 J background. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: In summary the data presented here clearly demonstrate that KATNAL1 plays an important role in a variety of neuronal processes including neuronal migration, neuronal morphology and ependymal ciliary function. The downstream effect of these defects leads in turn to a number of behavioural changes including in learning and memory, reaction to anxiogenic situations and circadian rhythms. These data therefore highlight how perturbations in KATNAL1 may play a role in neuronal dysfunction and demonstrates that the enzyme is a novel candidate in the study of behavioural and neurodevelopmental disorders.", "Title: Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals\nPassage: Relationship conflict , discord or loss can cause grief and situational psychological stress, and are all associated with increased risk of suicide . Unhealthy relationships can also be a risk factor. Violence, including sexual violence, against women is a common occurrence and is often committed by an intimate partner. Intimate partner violence is associated with an increase in suicide attempts and suicide risk. Globally 35% of women have experienced physical and/or sexual violence by an intimate partner or sexual violence by a non-partner . Title: Evaluating DREAMS HIV prevention interventions targeting adolescent girls and young women in high HIV prevalence districts in South Africa: protocol for a cross-sectional study", "Passage: \"once\", or \"more than once\". A positive answer to any of the items leads to a woman being classified as having experienced IPV. Only women reporting having a boyfriend, husband, or having had sex with a man are asked these questions. Gender norms are measured using the gender equitable men scale, this scale consists of 6 items relating to norms about male-female relationships and interactions. The scale asks respondents how much control their partners have over them in their relationships in relation to the clothes they wear, decisions made in the relationship and who they can spend time with outside Title: Rural Youth Violence: It Is a Public Health Concern!", "Passage: differences when it comes to youth involvement in violence that also need to be examined through a rural lens. We need to determine if the current findings based in urban contextsincluding that males are two to five times more likely than females to be involved in nearly all acts of violence 27 and that males and females are involved in different types of violence 24 -are true for rural youth. Title: Life Chaos is Associated with Reduced HIV Testing, Engagement in Care, and ART Adherence Among Cisgender Men and Transgender Women upon Entry into Jail", "Passage: The following number of observations were missing these dependent variables: engagement in care . The same study found that transgender women were more likely to engage in HIV transmission risk behaviors compare to cisgender men. Transgender women experience disproportionate burden of HIV , and risk behaviors may drive gender disparities among criminal justice-involved PLH. Interpretation of our findings is subject to limitations. First, our data are cross-sectional, which limits our ability to make causal inferences. Second, the interview was done prior to release from jail, so some participants may incorrectly recall their history prior to incarceration. While the restrictive environment", "Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses\nPassage: serum can be quantified through calculations from the R max values. According to our results using reconstituted samples, the detection limit for high affinity, low picomolar binding antibodies in serum using SPR was \u03f3250 ng/l. Epitope mapping to elucidate both the specificity of the antibody responses and their diversities is crucial for obtaining antibodies with a desirable mechanism of action . Traditionally, the antigen-antibody contact surfaces have been determined by methods such as high resolution x-ray crystallography and site-directed mutagenesis . However, these methods are not applicable for our purpose, because our samples contain antibody mixtures. In addition, the amount Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: interactions between mouse serum IgGs and human IL-13. The binding interactions were monitored over 10-min association periods followed by 45-min dissociation periods. The binding response curves were obtained by measuring the binding of human IL-13 to IgGs captured on the biosensor surface that were titrated by 2-fold dilutions as follows: 100 nM ; 50 nM ; 25 nM ; 12.5 nM ; and 6.25 nM . Kinetic fit was performed on serum samples D and F-I using the 1:1 Langmuir kinetic binding model in the ProteOn analysis software, as illustrated by the black lines that overlay the response curves. Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: concentrations showed that the sensitivity of the method was \u03f331 ng of antigen-specific IgG per l of serum. This high sensitivity can facilitate the detection of less abundant IgGs exhibiting unique epitopes, maximizing the diversity of antibodies that can be recovered. After establishing the highly sensitive SPR and HDX LC/MS methods for detecting antigen-specific antibodies in serum, we tested their performance using sera from immunized mice. Nine serum samples collected from various strains of mice, which were immunized with human IL-13 using different protocols, were analyzed with these methods in a \"proof-of-concept\" study. These samples were previously classified as binders Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: Characterization of Serum IgG-Antigen Binding Kinetics-A small volume of each serum sample was diluted 1000-fold into the PBS/Tween/EDTA running buffer. Six diluted samples were then injected simultaneously over the six available vertical channels at a flow rate of 25 l/min, during which the IgGs were captured by the protein A/G. The capture time was monitored to achieve a high antibody surface density . Because of the high abundance of mouse IgGs in the serum samples, a capture time of \u03f3120 -150 s was sufficient to reach the targeted density level. Following a blank buffer injection of 180 s over the", "Title: CDC Summary 21 MAR 2020,\nPassage: The virus that causes COVID-19 is infecting people and spreading easily from person-to-person. Cases have been detected in most countries worldwide and community spread is being detected in a growing number of countries. On March 11, the COVID-19 outbreak was characterized as a pandemic by the WHOexternal icon. Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: It is currently unclear how 2019-nCoV is spread, but it is suspected to be transmitted through contact with infected respiratory secretions, like other known coronaviruses. There are instances of sustained human-to-human transmission across generations of cases, especially near the epicenter in Wuhan City. 21 Current evidence suggests that close contact with an infected person is a major factor in disease transmission. CDC defines \"close contact\" 33 as being in or within two meters of an area with a confirmed patient or being directly exposed to infectious secretions without appropriate PPE. Healthcare facilities in China have reported spread from person to Title: CDC Summary 21 MAR 2020,", "Passage: People who get a fever or cough should consider whether they might have COVID-19, depending on where they live, their travel history or other exposures. More than half of the U.S. is seeing some level of community spread of COVID-19. Testing for COVID-19 may be accessed through medical providers or public health departments, but there is no treatment for this virus. Most people have mild illness and are able to recover at home without medical care. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: close contact with one another through respiratory droplets produced when an infected person", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis", "Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China\nPassage: Text: China, with an estimated prevalence of all TB cases of 108 per 100,000 in 2010, has the second highest TB burden in the world, accounting for 13% of all cases worldwide . The World Health organization estimated that China had reached the targets of 85% treatment success by 1993 and 70% case detection rate by 2005 . National TB prevalence surveys were conducted in China in 1979 China in , 1990 China in , 2000 , and 2010 . Survey results provide more accurate estimates for TB prevalence rates than the WHO estimates and can be used to assess Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: including 19 new bacteriologically confirmed cases and 153 CXRAY suggestive bacteriologically negative cases. The survey also identified 11 existing cases registered on the national TB program. In addition, the survey found four cases with culture positive non-tuberculosis bacilli, and excluded them from TB patients. Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: The adjusted prevalence rate of bacteriologically confirmed cases in Shandong was lower than the WHO estimates for China in 2010 . But the national prevalence rates of bacteriologically confirmed cases, 119/100,000 in 2010 , was higher than the WHO estimate, 108/ 100,000, even the survey did not collect negative and extra-pulmonary TB cases. Vietnam reported similar findings in its 2006 survey . One reason is that prevalence surveys results are based on active case finding while WHO estimates are based on notification rates from passive case finding. A re-evaluation of the reported TB prevalence in China is needed based on Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: Another notable change is the sharp decline of the proportion of sputum positive cases, which accounted for 30.5% of all cases in the 2000 survey but was reduced to 6.6% in the 2010 survey. The proportion of notified sputum cases out of all TB cases in Shandong also declined from 80.9% in 2005 to 64.6% in 2010 .", "Title: 1918 Influenza: the Mother of All Pandemics\nPassage: in understanding the risk of H1N1 \u201cswine \ufb02u\u201d emergence Title: The origins of the great pandemic\nPassage: Re-reading this list of 'clinical features', in the year 2018, and bearing in mind that, just a year thereafter, the influenza pandemic of 1918-19 began to take its toll, one of the five features stands out clearly from the page. That feature was cyanosis. It was referred to frequently, as the article progressed: Title: 1918 Influenza: the Mother of All Pandemics\nPassage: humans and swine were immunologically naive in 1918 Title: The 1918 Influenza Pandemic: Looking Back, Looking Forward", "Passage: The influenza virus is remarkable for its ability to infect a variety of animal species, from bats to birds to mammals. Although successful cross-species transmission events may be rare, they play a key role in the genesis of new pandemic strains. Nelson and Worobey discussed different lines of evidence informing the origins of the 1918 virus, including the genetic make-up of the 1918 virus and other pandemic strains, the characteristics of influenza receptors across different influenza hosts, and the frequency of cross-species transmission events. They concluded that the pandemic virus must have emerged in mammals just before 1918, most likely", "Title: Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015\nPassage: Many countries now include laboratory-confirmed influenza tests as part of their national influenza surveillance programs, and this information is communicated through the Internet to the public health community on a weekly basis . In contrast, the surveillance in developing countries is largely falling behind due to the little data available on the surveillance of influenza activity in the regions. Because only a small proportion of influenza infections are confirmed through laboratory findings, empirical data on laboratory-confirmed seasonal influenza are limited by very low and possibly non-systematic case ascertainment. In general, little information is available in the literature regarding the association Title: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data", "Passage: The threat of pandemic influenza has led to extensive efforts to strengthen the global influenza surveillance , including the development of novel syndromic surveillance systems intended to identify potential outbreaks and track influenza in the population. Some focus on identifying influenza-like-illness in clinical and other settings, while others search the Internet to identify disease outbreaks that might not have been recognized by the authorities . Having found high correlations with traditional surveillance systems and noting the benefits of timeliness and low cost, Internet-based surveillance systems have been widely recognized as important supplementary data sources for influenza surveillance . Title: Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015", "Passage: only rely on increasing numbers of influenza-like illness cases because non-specific ILI-like symptoms may be caused by etiologies other than influenza . As a result, many countries collect data on laboratoryconfirmed influenza infection parallel to clinical surveillance to provide more accurate and timely information about influenza virus activity than information from conducting clinical surveillance alone. Although there has been important progress in influenza surveillance systems in recent years, the volume of information on the surveillance of ILI and laboratoryconfirmed virus activity remains too sparse for detailed analyses at the province and city levels even in developed countries . Title: A systematic review of studies on forecasting the dynamics of influenza outbreaks", "Passage: ILI and acute respiratory tract infections rely on reports from general practices, family doctor clinics, diagnostic test laboratories, and public health departments for influenza surveillance. 3, 4, 14 There is typically 1-2 week lag in the publishing of reports, and reported cases are sometimes retrospectively adjusted. Additionally, the exact number of influenza cases is unobtainable due to unreported cases and asymptomatic infections.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: One drawback of an Ad5 vector is the potential for preexisting immunity, so alternative adenovirus serotypes have been explored as vectors, particularly non-human and uncommon human serotypes. Non-human adenovirus vectors include those from non-human primates , dogs, sheep, pigs, cows, birds and others . These vectors can infect a variety of cell types, but are generally attenuated in humans avoiding concerns of preexisting immunity. Swine, NHP and bovine adenoviruses expressing H5 HA antigens have been shown to induce immunity comparable to human rAd5-H5 vaccines . Recombinant, replication-defective adenoviruses from low-prevalence serotypes have also been shown to be efficacious. Low prevalence Title: Viral vector-based influenza vaccines", "Passage: Ad-HA vaccines Adenoviruses expressing HA genes of a number of different subtypes ) have been tested in various animal models. In the first study with rAd5, a vaccine that expressed the HA gene of an A influenza virus of swine-origin protected mice from challenge infection with a heterologous A virus. 196 A rAd expressing the HA gene of a different A virus was shown to be efficacious in pigs, 197 even in the presence of maternal antibodies. 198 Adenovirus vaccines expressing the HA gene of A/PR/8/34, completely protected mice from homologous challenge infection. 195, 199, 200 Pigs could also be Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: Although a strong antibody response is important for immediate and long-term protection against influenza viruses, the induction of early cellular immune responses following vaccination may enhance clearance of virus-infected cells following H5N1 influenza virus infection. T-cell responses were assayed using an enzymelinked immunosorbent spot assay to detect secretion of interferon gamma by activated lymphocytes. Splenocytes were obtained from mice vaccinated at days 8, 10, 14, and 21 with 10 10 vp/mouse of PAV3-HA or AdHu5-HA and the cells were restimulated with pools of overlapping peptides corresponding to the entire H05-HA protein. The peptide corresponding to the immunodominant H5N1-H05 HA epitope Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: immune responses could be maintained. PAV3-HA afforded full protection in mice challenged with 100 LD50 of H5N1-H05 virus 12 months post-immunization whereas 50% of mice vaccinated with AdHu5-HA succumbed . Higher HI antibody titers for PAV3-HA compared to AdHu5-HA ) may have translated directly to the improved survival observed with the PAV3-HA vaccine. NAB titers were 23615 and 10611 for AdHu5-HA . An ELISA assay was also performed to detect total IgG antibody titres against the H5N1-HA antigen. Serum was obtained from mice 25 days and 1 year post-vaccination, and unvaccinated control mice . Total antibody titers were significantly lower", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: HCoV-OC43 and HCoV-HKU1 usually cause self-limiting upper respiratory infections in immunocompetent hosts and occasionally lower respiratory tract infections in immunocompromised hosts and elderly . In contrast, SARS-CoV and MERS-CoV may cause severe lower respiratory tract infection with acute respiratory distress syndrome and extrapulmonary manifestations, such as diarrhea, lymphopenia, deranged liver and renal function tests, and multiorgan dysfunction syndrome, among both immunocompetent and immunocompromised hosts with mortality rates of \u223c10% and \u223c35%, respectively . On 31 December 2019, the World Health Organization was informed of cases of pneumonia of unknown cause in Wuhan City, Hubei Province, China . Subsequent virological testing Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: Abstract: Human coronavirus is a known cause of influenza\u2010like illness . In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR\u2010positive for HCoV. The distribution of species was as follows: HCoV\u2010OC43 , HCoV\u2010229E , HCoV\u2010NL63 , and HCoV\u2010HKU1 . We did not observe species\u2010specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV\u2010HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness. Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: The Alphacoronaviruses HCoV 229E and NL63, as well as the Betacoronaviruses HKU 1 and OC43, can infect humans and cause the common cold. In order to investigate the potential maternal-fetal transmission of human coronaviruses during pregnancy, Gagneur et al. evaluated 3 types of maternal-infant paired specimens that included maternal vaginal and respiratory specimens that were obtained during labor, as well as gastric samples from the newborn infants. These specimens were evaluated for the presence of HCoV 229E, OC-43, NL63 and HKU 1 using RT-PCR methodology. Between the period from July 2003 to August 2005 the authors examined 159 mother-infant dyads. Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: to be the most common species among adults, as has been reported elsewhere. 8, 9, 11, 12, 14 HCoV-OC43 and HCoV-229E were the most common strains in alternate seasons, reflecting a season-to-season variability of HCoV strain circulation that has been reported in other multiyear studies. 4 8 The mechanisms by which this particular species elicits these symptoms are not known.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: SARS-CoV that includes the split orf8b , civet SARS-CoV , two bat SARS-related-CoV containing full-length orf8 , 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5 ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Yunnan strains such as the WIV1 had no such deletions and can use human ACE2 as a cellular entry receptor. It is interesting to note that the two bat SARS-related coronavirus ZXC21 and ZC45, being closest to 2019-nCoV, can infect suckling rats and cause inflammation in the brain tissue, and pathological changes in lung & intestine. However, these two viruses could not be isolated in Vero E6 cells and were not investigated further. The two retained deletion sites in the Spike genes of ZXC21 and ZC45 may lessen their likelihood of jumping species barriers imposed by receptor specificity. Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Wild animal, bats is the most possible host of the 2019-nCoV. It requires further confirmation whether pneumonia infected by the 2019-nCoV is transmitted directly from bats or through an intermediate host. It is believed that clarifying the source of the virus will help determine zoonotic transmission patterns .", "Title: CEACAM1 in Liver Injury, Metabolic and Immune Regulation\nPassage: CEACAM1 is the only member of the CEA family that is expressed on activated CD4 + and CD8 + T cells, where it is rapidly upregulated upon TCR stimulation . In naive CD4 + T cells, CEACAM1 is expressed at very low levels, and is stored intracellularly in endosomal compartments . In activated T cells, CEACAM1 shows overlapping expression kinetics with the activation marker CD69 and precedes the expression of cytotoxic T-lymphocyte-associated protein 4 . This indicates that the inhibitory form, CEACAM1-L, can interfere with T cell activation prior to CTLA-4, and is therefore, an independent immune checkpoint regulator. CEACAM1-S Title: CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production", "Passage: causes cell activation 19,26 . CEACAM1 is expressed by a broad range of cell types, including angiogenically activated endothelia/lymphendothelia, various leukocyte subpopulations, normal epithelial cells and tumour cells 16 . Although Ceacam1 \u00c0 / \u00c0 mice do not exhibit this broad CEACAM1 expression, they develop normally and, in the absence of specific challenges, show no signs of disease 27 . CEACAM1 has been described primarily as a regulator of T cells in the gut 20, . Expression of CEACAM1-L inhibits T-cell proliferation and therefore prevents inflammatory bowel disease 30 . Expression of CEACAM1-S is essential for the development of follicular Title: CEACAM1 in Liver Injury, Metabolic and Immune Regulation", "Passage: CEACAM1 is expressed in T, B, NK, and dentritic cells, and in granulocytes, monocytes and macrophages . In na\u00efve lymphocytes, CEACAM1 is expressed at low levels, but undergoes a rapid upregulation upon cellular activation. In contrast, in granulocytes, CEACAM1 is a differentiation antigen that controls granulopoiesis and delays neutrophil apoptosis . CEACAM1 is generally associated with protection against hyperinflammation that results from either inappropriate expansion of cellular precursors such as in dysregulated granulopoeiesis and neutrophilia in Ceacam1 \u2212/\u2212 mice, associated with enhanced IL-1\u03b2 production in response to stimulation of toll-like receptor 4 or exaggerated effector T cell responses or dysfunctional Title: CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production", "Passage: CEACAM1 is expressed on B-cell subsets. We first analysed CEACAM1 expression on various cell populations in the peripheral blood of wild-type mice. Erythrocytes stained negative for CEACAM1 . As previously reported , high levels of CEACAM1 expression were detected on blood granulocytes and monocytes with the anti-CEACAM1-specific monoclonal antibody . Cells from Ceacam1 \u00c0 / \u00c0 mice stained negative for CEACAM1 . Next, we analysed CEACAM1 expression on lymphoid cells in the blood. CD90.2 cells, representing primarily T cells, showed weak CEACAM1 expression by individual cells , a finding suggesting that various T-cell subpopulations may differentially express CEACAM1. B cells", "Title: Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance\nPassage: Among persons who reported ILI, the most common symptom besides feverishness was sore throat , headache and cough . Signs of lower respiratory tract infection, such as difficult or fast breathing and wheezing, were less common among person who reported ILI than those with pneumonia. The mean duration of illness among persons with ILI was seven days ; more than half of person who reported an ILI had symptoms for seven days or more. Title: Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia", "Passage: Signs and symptoms of upper and/or lower respiratory tract infection, along with systemic involvement in the form of fever, myalgia, and headache, are usually the main presenting features of the disease. In the context of an outbreak, otherwise healthy subjects presenting with a self-limited acute febrile respiratory illness usually require no further diagnostic procedures. In two retrospective studies that examined which clinical signs and symptoms are most predictive of influenza infection in patients with influenza-like illness, cough and fever were the only symptoms significantly associated with a positive PCR test for influenza . In another study, no isolated symptom or Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: Association in 2006. 17 In the guideline, the clinical symptoms and signs for the diagnosis of childhood CAP include fever, cough, tachypnoea , difficulty breathing and/or lower chest wall indrawing. X-ray evaluation has been carried out when necessary. The study protocol was approved by the medical ethical committees of the hospitals. Written informed consent was obtained from the parents or legal guardians of the children. Title: Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance\nPassage: The most common symptoms reported by persons with pneumonia were difficult breathing , cough , and feverishness . The mean duration of illness of all persons with pneumonia was 13 days ; more than one-quarter had symptoms for seven days or more.", "Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: ranged from 36%-60% overall, which is alarmingly high compared with all previous outbreaks of human cases of seasonal influenza in the United States, for which the CFR has ranged from 0.04%-1.0% . This high level of illness severity and high mortality rate was unexpected and increased disease burden, resulting in concern among clinicians and public health officials; however, the risk factors that are most highly associated with the deaths from avian influenza were not clear. Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses", "Passage: Five time periods that are useful for public health surveillance were evaluated. For the H5N1 group, with the exception of the median days from onset to antiviral treatment, there were differences between the fatalities and survivors in other median days, including days from onset to hospitalization vs. 5 days, p = 0.023]; days from onset to confirmation of infection Figure 4 ). Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses", "Passage: For the H7N9 group, the median number of days from onset to confirmation of infection in the fatality groups was slightly longer than that of survivors vs. 8 days, p = 0.011]; however, the median number of days from onset to outcome vs. 31 days, p < 0.001] and number of hospitalization days vs. 25 days, p < 0.001] in the fatality groups was slightly less than those relating to survivors, respectively . Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: In the H5N1 group, the CFR was statistically significantly higher in the index fatalities than in the secondary fatalities vs. 43.3% , respectively, p < 0.001], as was the number of people with comorbidities vs. 0.0% , respectively, p = 0.043]; however, there were no differences between H7N9 virus index and secondary fatalities in the CFR and underlying diseases .", "Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: and how these influence the process warrant a more in-depth examination. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: The health-evidence.ca registry was used to identify gaps and areas of wealth in the public health review literature. Each of the 21 Focus of Review topic areas were searched, and the quantity and proportion of reviews rated methodologically strong, moderate, and weak were identified. Three categories were used to define availability of reviews within each topic area: few, representing 1-150 reviews; moderate, representing 151-300 reviews; and, many, representing topic areas possessing greater than 301 reviews. Reviews that addressed multiple topics were accounted for within each topic area that they addressed . Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: The 21 Focus of Review topic areas were further broken down into 291 sub-topic categories. There were 34 sub-topics with no reviews available including: hormone replacement therapy, infertility, Norwalk virus, autism, and elder abuse, among others . The 21 Focus of Review topic areas that had sub-topics with no review included adult health, communicable disease/infection, dental health, environmental health, food safety and inspection, parenting, and senior health. The largest proportion of sub-topic with no review was observed within communicable disease/infection . Adult health was ranked sixth and communicable disease/ infection ranked tenth by registered users. Parenting was ranked as a Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: As of April 1, 2011 there were 2, 175 systematic reviews evaluating the effectiveness of public health and health promotion interventions indexed in the health-evidence. ca registry. Table 3 provides an overview of the availability of reviews within each of the 21 Focus of Review topic areas. Figure 3 depicts the relationship between registered users' interests, visitor searches, and available reviews within each of the 21 topic areas.", "Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: during March 17-28, the WHO Director-General declared on March 29, 2016 the end of the Public Health Emergency of International Concern regarding the EVD outbreak in West Africa . Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak", "Passage: The response by the US arguably began in March 2014 when CDC deployed personnel to investigate Ebola cases in Guinea, and further on July 9, 2014 with the activation of CDC's Emergency Operations Center. However, because EVD was largely out of the public's eye until the fall of 2014, its response was similarly delayed. That is, the peak number of EVD cases in Liberia was September 21, 2014; one week after President Obama's announcement to commit 3000 troops and provide additional aid to the Ebola response effort and one month after WHO declared it a public health emergency of international Title: Chinese Public Attention to the Outbreak of Ebola in West Africa: Evidence from the Online Big Data Platform", "Passage: This current Ebola outbreak started in Gu\u00e9ck\u00e9dou and Macenta districts of Guinea during December 2013 , and WHO proclaimed the EVD outbreak on 23 March 2014. As the situation deteriorated, from all of the available evidence, Director-General Margaret Chan of WHO defined the epidemic to be a Public Health Emergency of International Concern. Figure 1 Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: WHO declared the Ebola epidemic over on March 29, 2016 with 28,646 cases and 11,323 deaths across 10 countries and three continents. Of the three countries most widely affected, Liberia was first to successfully control the epidemic , which was before the key indicator data were collected . The epidemic in Sierra Leone and Guinea was largely controlled by April 2015, but experienced sustained transmission into November 2015.", "Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: A total of 23,646 of MERS-CoV suspected cases were included in this study, of which 52.3% were males and 47.7% were females . e age of individuals with suspected cases ranged between 0 to 92 years with a mean age of 43. 23 e adjusted odds of MERS-CoV remained significant among different age groups; the odds of patients aged between 20-40 years increased threefold , whereas in the age group of 41-60 years, it increased further to a risk that was six times higher Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: ese data agreed with a previous surveillance study, which stated that the majority of confirmed cases of MERS-CoV were reported among people aged 40 and above . In 2016, only 9 of 552 cases of MERS-CoV infection were found among pediatric patients. Moreover, the study which was conducted in King Fahad Medical City in Riyadh between January 2012 and December 2013 did not report any MERS-CoV cases among children . e study which was conducted across the Gulf countries for four years by Mahmoud Aly et al. between 2012 and 2016 suggests that the prevalence and distribution of MERS-CoV were Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: the highest-risk in elderly aged 60 years or above . Similar to our results, this study also reported the highest number of confirmed cases during the summer season .", "Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data\nPassage: It is interesting to note that on average, our simple rules yielded a PPV of 0.84 and an NPV of 0.75. This means that on average, rules will correctly predict an abnormal laboratory result 5 times out of 6 and correctly predict a normal result 3 times out of 4. While not good enough to replace testing , these observations raise the question of how much better prediction can get. Integration of information not considered in the present study, including vital signs, chief complaints, and physical findings, may improve prediction by these methods. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: All tests had either two or three possible response values. For tests with three values, we performed two separate rule searches: one for high vs. not high-i.e., grouping normal and low-and one for low vs. not low. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: We based our study on 10 years of records from the Beth Israel Deaconess Medical Center , a 585-bed tertiary care center in Boston, MA. We first anonymized records and reconciled test names . Informed consent was not obtained because patient records/ information was anonymized prior to analysis. Each blood test , over 69.4 million in all, was marked as an in-house test or a sendout . For each test, we compiled a list of all instances in which the test was ordered and performed. For each instance, we recorded the patient's age, gender, and any diagnoses or other blood-test Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: We used four types of input-age, gender, diagnoses , and results of laboratory tests on blood samples added to the record in the seven days before a given test was ordered-to build simple, robust models for whether the result of a test would be within the reference interval or outside of it in a given direction , treating high and low results separately.", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: The field of 'virus dynamics' was first developed to describe the mechanistic underpinnings of long-term patterns of steady-state viral load exhibited by patients in chronic phase infections with HIV, who appeared to produce and clear virus at equivalent rates . Models of simple target cell depletion, in which viral load is dictated by a bottom-eLife digest Bats can carry viruses that are deadly to other mammals without themselves showing serious symptoms. In fact, bats are natural reservoirs for viruses that have some of the highest fatality rates of any viruses that people acquire from wild animals -including rabies, Ebola and Title: Computational Approaches and Challenges to Developing Universal Influenza Vaccines", "Passage: was introduced in 2004 to study \"how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viral phylogenies\" . Dynamics of influenza virus infections and transmissions at individual-level , population-level , or ecology-level have been studied . Specially, phylodynamics have been used to study factors of interest on some viral phenotypes, including virulence, viral transmissibility, cell or tissue tropism, and antigenic phenotypes that can facilitate immune escape, etc. . Details of methods and examined significant factors can be found in these reviews . Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: The findings may help to explain why bats are often the source for viruses that are deadly in humans. Learning more about bats' antiviral defenses and how they drive virus evolution may help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. More studies are needed in bats to help these efforts. In the meantime, the experiments highlight the importance of warning people to avoid direct contact with wild bats. up resource supply of infection-susceptible host cells, were first developed for HIV but have since been applied to other chronic infections, including Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: a spatially-explicit, stochastic reconstruction of our mean field model. In spatial simulations, rates of antiviral acquisition were fixed at fitted values for r and \" derived from mean field estimates, while transmission rates were fixed at values ten times greater than those estimated under mean field conditions, accounting for the intensification of parameter thresholds permitting pathogen invasion in local spatial interactions . In immune capable time series, spatial antiviral cells acted as 'refugia' which protected live cells from infection as each initial epidemic wave 'washed' across a cell monolayer. Eventual birth of new susceptibles from these living refugia allowed for", "Title: Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR\nPassage: of the three assays. Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case\nPassage: The correlation between viral load and quantitative proinflammatory factors profile was analyzed by Pearson's correlation test using Instat software . Differences were considered significant at p,0.05. Figure S1 The distribution of viral load in selected tissue samples. The viral HA gene and b-actin gene copies in tissues were determined by quantified real-time RT-PCR. The ratios between HA and b-actin gene copies which was showed by logarithm presented the viral-load level in different tissue. Found at: doi:10.1371/journal.pone.0013315.s001 Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: To ascertain the involvement of cellular factors in TGEV RNA synthesis, TGEV 3' and 5' genome ends were used as baits for RNA affinity protein purification . Of the ten cellular proteins pulled down with either genome end, poly-binding protein , hnRNP Q, and glutamyl-prolyl-tRNA synthetase were confirmed to enhance TGEV infection through their respective interactions with the TGEV 3' end, while glyceraldehyde 3-phosphate dehydrogenase -originally employed as a control-was discovered, surprisingly, to have a diminishing effect on TGEV infection instead . Title: Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR", "Passage: Another study showed that the relationship between viral loads and multiple virus infections is virus specific . The limited sample size of our study did not allow us to further explore viral load in relation to each different virus, which might explain why we did not see an overall change in influenza or RSV viral loads in cases of viral coinfection.", "Title: Human core duplicon gene families: game changers or game players?\nPassage: The RANBP2 protein encoded by the progenitor gene is primarily localized within the periphery of the nuclear envelope and is thought to be required for cargo import and export . Hence, the RGPD gene family members may be modifiers of this function. Interestingly, RANBP2 was also shown to be involved in resistance against Simian Immunodeficiency Virus . It is thus possible that the expansion of RGPD genes is the result of an arms race between virus evolution and host resistance acquisition. The Ranbp2 knockout in mice is homozygous lethal. Title: Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes", "Passage: As summarized in Table 1 , RanBP2 seems to be generally important for nuclear import of HIV-1 and HIV-2, but so far there is less evidence that it is important for SIVs from monkeys. We next tested whether great ape SIVs are dependent on RanBP2 for optimal entry. We used a lentiviral shRNA system to knockdown RanBP2 in 293T cells . The knockdown of RanBP2 is known to be toxic to cells , so we tested three different RanBP2 shRNA constructs for their general effect on cell proliferation using an MTT assay . Compared to a non-targeting shRNA control, the Title: RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders", "Passage: Similarly, it should be established whether repeat binding proteins, such as MBNL, which are known to localize in both the nucleus and cytoplasm , play a role in RAN translation. The question of whether these proteins participate directly in the initiation event or facilitate recruitment of key initiation factors to the expanded repeats still needs to be answered. Title: Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes", "Passage: Introduction RanBP2 is the major constituent of the cytoplasmic filaments extruding from the mammalian nuclear pore complex, where it mediates cargo import and export . Depletion of RanBP2 negatively affects HIV-1 and HIV-2 infection and nuclear import . Although HIV-1 can use other redundant pathways for import, pathways not involving RanBP2 lead to suboptimal chromosomal integration sites for the HIV-1 genome . The interaction between RanBP2 and HIV-1 may not occur strictly at the nuclear pore. It was recently reported that the Kinesin-1 motor, KIF5B, relocalizes RanBP2 to the cytoplasm during infection . As summarized in Table 1 , RanBP2", "Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China\nPassage: The crude prevalence rate in Shandong in 2010 of sputum positive cases was 22.1 , bacteriologically confirmed cases was 36.8 , and all cases were 337.1 per 100,000 in adult population . The adjusted prevalence rates of the whole population in Shandong were17.8 , 27.8 and 239.4 per 100,000 in 2010. A remarkable decline of 82.0%, 80.2% and 31.4% was observed in TB prevalence rates of sputum positive, bacteriologically confirmed, and all cases, respectively, compared to the adjusted rates in 2000 . Large declines were observed in males between 40 and 65 years old, and in females over 60 years Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: Another notable change is the sharp decline of the proportion of sputum positive cases, which accounted for 30.5% of all cases in the 2000 survey but was reduced to 6.6% in the 2010 survey. The proportion of notified sputum cases out of all TB cases in Shandong also declined from 80.9% in 2005 to 64.6% in 2010 . Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: Three sputum specimens of all suspected cases were collected and sent for smear microscopy and culture. RESULTS: Adjusted prevalence rate of bacteriologically confirmed cases was 34 per 100,000 for adults in Shandong in 2010. Compared to the 2000 survey, TB prevalence has declined by 80%. 53% of bacteriologically confirmed cases did not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65\u2019s. CONCLUSIONS: The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to identify TB Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: This study has shown that the prevalence of bacteriologically confirmed TB in Shandong has reduced substantially over the last decade. Importantly, the majority of these cases did not present with persistent cough and the proportion of sputum positive cases has declined sharply. Further studies are recommended to assess the feasibility of adopting CXRAY in the existing health care services to detect TB cases and the cost effectiveness of such intervention.", "Title: Identification of RNase L-Dependent, 3\u2032-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells\nPassage: The arthropod-borne SINV is a small, enveloped, positive, single-stranded RNA virus and is the prototype for the alphavirus genus. Alphaviruses represent a group of widely distributed human and animal pathogens, which pose a serious public health threat . Some of them induce febrile and arthritogenic diseases, while others can cause highly debilitating diseases, such as encephalitis. The SINV genomic RNA is capped and polyadenylated and is infectious as naked RNA. Upon entry into the cytoplasm by endocytosis, the host translational machinery recognizes the genomic RNA, and four nonstructural proteins are produced . Their expression is sufficient for the establishment of Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: highest for Bunya-, Flavi-and Arenaviruses in rodents; Flavi-, Bunyaand Rhabdoviruses in bats; and Herpesviruses in non-human primates . Of 586 mammalian viruses in our dataset, 263 have been detected in humans, 75 of which are exclusively human and 188 zoonotic-defined operationally here as viruses detected at least once in humans and at least once in another mammal species . The proportion of zoonotic viruses is higher for RNA than DNA viruses. The observed number of viruses per wild host species was comparable when averaged across orders, but bats, primates, and rodents had a higher proportion of observed zoonotic viruses compared Title: Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases", "Passage: In addition to infecting humans, many nairoviruses have been directly associated with other vertebrate hosts. CCHFV, for example, is reported to infect a wide array of mammalian species , however disease is restricted to humans. Importantly, CCHFV maintenance and transmission relies on asymptomatic circulation among a number of hosts, including small mammals, reptiles, and livestock . NSDV and DUGV also infect livestock, with NSDV causing severe gastroenteritis in sheep and goats. Nairoviruses have been isolated from bats , and are often detected in vertebrate associated ectoparasites; Kupe virus , for example, was isolated from ticks infesting cattle, sheep, and goats, Title: Distribution and characteristics of rodent picornaviruses in China", "Passage: Increasing attention focused on rodents as the natural hosts of many important zoonotic virus. Firth et al. 25 identified a wide range of known and novel viruses from groups that include important human pathogens, including sapoviruses, cardioviruses, kobuviruses, parechoviruses, rotaviruses, and hepaciviruses carried by commensal Rattus norvegicus in New York city 25 . The role of rodent picornaviruses in the evolution, transmission, and biology of picornaviruses remains unclear. Drexler et al. 11 conducted a targeted search for hepatoviruses in 15,987 specimens of 209 small mammal species, and ancestral-state reconstructions suggested a hepatovirus origin in small insectivorous mammals, and a rodent", "Title: Multi-criteria decision analysis as an innovative approach to managing zoonoses: results from a study on Lyme disease in Canada\nPassage: the validity of analysis. Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: of imputation were used to obtain the ORs. The imputation had little effect on the univariable analyses, therefore summary statistics from these analyses are based on the observed data. In a sensitivity analysis, a complete case analysis was performed and adjusted ORs were estimated for all of the baseline variables excluding BMI. Estimates similar to those based on multiple imputation were obtained . Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: As proof of principle for GLM, we first tested it on the anion gap, a result calculated by subtracting the serum concentrations of the anions chloride and bicarbonate from those of the cations sodium and potassium, and confirmed that our methods found a rule for elevated anion gap based on these four items. Title: The Screening Research of NF-\u03baB Inhibitors from Moutan Cortex Based on Bioactivity-Integrated UPLC-Q/TOF-MS\nPassage: Analysis. The test results were represented with mean \u00b1 SEM. And t-test was used for comparison of significant differences among different groups. SPSS v.18.0 statistical analysis software was used for statistical analysis. Results with values of P < 0.05 were considered statistically significant.", "Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking\nPassage: where N \uf02b is the total number of the interactive NR-drug pairs investigated while N \uf02b \uf02d the number of the interactive NR-drug pairs incorrectly predicted as the non-interactive NR-drug pairs; N \uf02d the total number of the non-interactive NR-drug pairs investigated while N \uf02d \uf02b the number of the non-interactive NR-drug pairs incorrectly predicted as the interactive NR-drug pairs. Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking", "Passage: where N \uf02b is the total number of the interactive NR-drug pairs investigated while N \uf02b \uf02d the number of the interactive NR-drug pairs incorrectly predicted as the non-interactive NR-drug pairs; N \uf02d the total number of the non-interactive NR-drug pairs investigated while N \uf02d \uf02b the number of the non-interactive NR-drug pairs incorrectly predicted as the interactive NR-drug pairs. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences . N is also reported to interact with actin microfilaments, and the SUMO-1 protein . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: It has also been observed that the N protein of several coronaviruses can localize in the nucleolus where it may perturb cell cycle activities of the host cell for the benefit of viral mRNA synthesis . IBV N, for example, appears to target CDK2, cyclins A and D1 for proteasomemediated degradation and cause the accumulation of hypophosphorylated retinoblastoma , resulting in the downregulation of CDK1, cyclins E and B1 .", "Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis\nPassage: However, to our knowledge, there is no evidence of sustained onward transmission of the 1918 pandemic virus outside of North America, where the virus sustained long-term circulation in pigs and became established as the \"classical\" H1N1 swine influenza virus lineage , which continues to circulate in North American and has been introduced into Asian swine. Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: The simultaneous outbreaks of influenza in humans and pigs during the 1918 pandemic naturally raised questions about whether the virus had transmitted from pigs to humans, or humans to pigs. At the time, Koen noted that the flu outbreaks appeared to represent a novel disease in pigs, whereas humans had a long history of influenza pandemics, which suggested that humanto-swine transmission was more likely. Almost a century later, the reconstruction of a 1918 virus from human tissues preserved in Alaskan permafrost and autopsy blocks indicated that the virus's genes appeared to have avian origins . But this did not end Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: Overall, the most parsimonious explanation is that the genes of the 1918 virus transmitted largely from birds to humans at the start of the pandemic, and from humans to swine once the pandemic was widespread in humans, with no role played by swine in the origins of the human pandemic . In addition to Koen, there is a reference to an infection with influenzalike disease in swine near the China-Russia border during the second global wave of the pandemic during October 1918 and an independent description of influenza in European swine in 1918 by Altmann Aladar, a Hungarian veterinarian . Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: coincidence if not suggesting a close relation between the two conditions\" . Confirmation that influenza was circulating in US swine was achieved in 1931 when Richard Shope isolated the first influenza virus from pigs . Two years later, the H1N1 virus was isolated from humans . It was later demonstrated that sera from humans infected with the 1918 pandemic virus could neutralize the swine virus .", "Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: Influenza is an infectious disease affecting mainly upper respiratory tract worldwide. Influenza virus causes between three and five million severe cases and an estimated 250,000-350,000 deaths annually. In the European Union, there are between 40,000 and 220,000 annual deaths attributable to influenza. However, mortality is only the tip of the iceberg in terms of the disease burden, since influenza also causes a decrease in functional status and increased dependency in the elderly . Estimating the burden of disease caused by influenza is difficult because many cases do not require medical care, or no confirmatory laboratory tests are widely performed to Title: Use of daily Internet search query data improves real-time projections of influenza epidemics", "Passage: Seasonal influenza remains an important infectious cause of morbidity and mortality . In the USA alone, estimates of annual incidence range from 9.2 million to 35.6 million cases, resulting in 140 000 to 710 000 hospitalizations and 12 000 to 56 000 deaths . Title: Forecasting the 2013\u20132014 Influenza Season Using Wikipedia\nPassage: hospitalized from seasonal influenza complications, and 3,000-49,000 people die each year . The result is a significant public health and economic burden for the U.S. population . Title: Identification of pneumonia and influenza deaths using the death certificate pipeline", "Passage: Pneumonia and influenza are serious public health threats and are a cause of substantial morbidity and mortality worldwide; for instance, the World Health Organization estimates seasonal influenza causes between 250,000 to 500,000 deaths worldwide each year while pneumonia kills more than 4 million people worldwide every year . Worldwide, the morbidity and mortality of influenza and pneumonia have a considerable economic impact in the form of hospital and other health care costs. Each year in the United States approximately 3 million persons acquire pneumonia and, depending on the severity of the influenza season, 15 to 61 million people in the", "Title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection\nPassage: Non-influenza related upper respiratory infections are universally experienced illnesses that, despite their typically selflimited nature, lead to billions of dollars of lost income, and predispose to serious illnesses including pneumonia. When influenza is responsible, pandemics can result and cause millions of deaths. In 2009, a novel H1N1 influenza virus emerged and rapidly spread worldwide, causing excess mortality in children and young adults. Although the global estimate of deaths has been lower than seen in several previous pandemics, the number of life years lost is estimated to be five times higher than those lost to seasonal H1N1 viruses and comparable to Title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection", "Passage: All subjects provided written, voluntary informed consent in the presence of an ombudsman. The study was approved by Wilford Hall Medical Center/Brooke Army Medical Center Institutional Review Board . Gender and ethnicity were self-reported. Per Department of Defense Directive 3216.02, for purposes of legal capacity to participate in DoD-conducted or -supported research involving human subjects, all active duty service members in a federal duty status are considered to be adults. The participation of such members is not subject to requirements regarding research involving children or minors. When service members are under 18 years of age, students at service academies, or Title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection", "Passage: Febrile Respiratory Illness Surveillance Update show a rate of febrile respiratory infection that increased in December of 2009, 82% of which was associated with adenovirus, with no influenza virus detected. Additionally, the use of oseltamivir, both for prophylaxis and for treatment, would have impacted both epidemiology and severity of illness. Finally, without inclusion of asymptomatic or minimally symptomatic individuals, conclusions can only be drawn about the scarcity of coinfections with individuals at the point of presentation to care. Title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection", "Passage: In summary, this epidemiologic survey of young adults in military training presenting with fever and URI demonstrated significant differences in 2009 H1N1 vs. adenovirus in terms of gender predilection and presenting symptoms. In addition, coinfections with 2009 H1N1 and adenovirus were rare despite high endemicity of adenovirus before and during the 2009 H1N1 epidemic, and, beyond a higher temperature on presentation, coinfections were not associated with increased clinical severity compared with adenovirus alone.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: an anti-IgE antibody elicited antibodies that bound purified IgE molecules , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. For example, immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes . Phage displaying or chemically Rubinchik and Chow conjugated to sperm antigen peptides or peptide mimics and gonadotropin-releasing hormone are also in development. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: an anti-IgE antibody elicited antibodies that bound purified IgE molecules , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. For example, immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes . Phage displaying or chemically Rubinchik and Chow conjugated to sperm antigen peptides or peptide mimics and gonadotropin-releasing hormone are also in development. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination . The phage particle is immunogenic without adjuvant in all species tested to date, including mice , rats , rabbits , guinea pigs , fish , non-human primates , and humans . Various routes of immunization have been employed, including oral administration as well as subcutaneous , intraperitoneal , intramuscular , intravenous , and intradermal injection ; no published study has directly Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination . The phage particle is immunogenic without adjuvant in all species tested to date, including mice , rats , rabbits , guinea pigs , fish , non-human primates , and humans . Various routes of immunization have been employed, including oral administration as well as subcutaneous , intraperitoneal , intramuscular , intravenous , and intradermal injection ; no published study has directly", "Title: School closures during the 2009 influenza pandemic: national and local experiences\nPassage: In the early phase of the pandemic, HK implemented aggressive strategies to attempt to contain and later on to mitigate the spread the virus. Once the first case due to indigenous transmission was confirmed on 10 June 2009, they moved from a \"containment phase\" to a \"mitigation phase\" designed to relieve disease burden and mortality, primarily based on NPI . The mitigation phase included: public health campaigns , medical resource mobilization, opening of eight designated fever clinics , and antiviral treatment of confirmed cases. In addition, there was an immediate proactive closure of kindergarten/primary schools for at least 2 weeks Title: Breaking the Waves: Modelling the Potential Impact of Public Health Measures to Defer the Epidemic Peak of Novel Influenza A/H1N1", "Passage: It has been shown before that so called targeted layered containment strategies, a combination of antiviral prophylaxis and non-pharmaceutical interventions, can be effective in reducing the transmission of pandemic influenza . We extended this approach by analyzing the effect of a more intensive phase including contact tracing, identification and management of contacts outside of the household , followed by household centred measures . Title: Modeling the effect of comprehensive interventions on Ebola virus transmission", "Passage: measures are a combination of early diagnosis, case isolation, contact precaution, awareness campaigns, and sanitary burial practices. Identifying infected people quickly by the polymerase chain reaction assay and isolating them to break chains of EVD transmission may be effective to control the outbreak. The effect of reducing the time between symptoms onset and diagnosis with rapid testing has also been investigated in the literature . Title: Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model", "Passage: Finally, scenario e demonstrates that containment is still possible even when the vaccine is completely ineffective in everyone -because of case isolation and isolation of contacts . Here, with 40 contact tracings possible per day, 55% of the replications nevertheless exhibited containment even with a vaccine which offered no protection whatever. With 90 contact tracings possible per day, all replications exhibited containment even assuming no vaccine protection.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: For viral vectors, the impact of cell-mediated immunity was more pronounced, and as depicted in Table 2 , almost always resulted in a reduction in the subsequent immune response. Presumably this is because viruses will induce neutralizing antibody on the first dose, and in subsequent doses this antibody will limit the number of transduced cells, therefore limiting the responses. This is particularly a problem with a common viral vector such as Ad, where a large proportion of the population will have immunological memory against common serotypes . As these authors conclude, it will be possible to utilize such vectors only Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: expressing tetC, induced much lower anti-tetC responses than mice that had not been primed. This argues strongly that prior immunological immunity to the vector can seriously dampen subsequent antigen-specific humoral responses. Whether the same is true for cellular responses was not evaluated. Title: Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus", "Passage: to EBOVGP when part of the mucin-rich region was deleted, possibly as a result of altered proteosomal processing of EBOVGP or direct deletion of T-cell epitopes. After decay of the primary cell-mediated immune response, a second vaccine dose boosted ELISpot responses to levels seen after primary vaccination; however, there was still no detectable cell-mediated immune response elicited by vectors expressing EBOVGP from position 3 and 6, indicating the requirement for higher EBOVGP levels in infected cells to generate detectable EBOVGP-specific cell-mediated immune responses.", "Title: Investments in respiratory infectious disease research 1997\u20132010: a systematic analysis of UK funding\nPassage: Tuberculosis also represents a substantial challenge to global health, accounting for 2.2% of all-cause DALYs lost world-wide, 1 and an estimated 1.4 million deaths in 2011. 3 The target of the WHO Global TB Plan is to reduce tuberculosis deaths to half of those recorded in 1990 by 2015, but it is thought that both Europe and Africa will fail to meet these goals. Control efforts are hampered by limited vaccine effectiveness, coinfection with HIV, insufficient diagnostic capacity in low income settings, prolonged treatment courses and the emergence of drug resistant strains. 3, 4 Globally an estimated 500,000 deaths annually Title: Mortality among patients with tuberculosis requiring intensive care: a retrospective cohort study", "Passage: Across the world tuberculosis remains an important public health problem, especially in developing countries. One third of the world's population is infected with Mycobacterium tuberculosis. Brazil is ranking 15 th among the 22 high-burden countries that collectively account for 80% of TB cases globally. The incidence of TB was of 50 cases/100,000 population/yr in 2006, and recently reached approximately 100 cases/ 100,000 population in the city of Porto Alegre . Every year, almost 2 million people die of TB, most of them in low-and middle-income countries. The annual death rate from TB in Brazil was estimated at 4.0/100,000 population/yr in Title: Investments in respiratory infectious disease research 1997\u20132010: a systematic analysis of UK funding", "Passage: 1 and an estimated 1.4 million deaths in 2011. 3 The target of the WHO Global TB Plan is to reduce tuberculosis deaths to half of those recorded in 1990 by 2015, but it is thought that both Europe and Africa will fail to meet these goals. Control efforts are hampered by limited vaccine effectiveness, co-infection with HIV, insufficient diagnostic capacity in low income settings, prolonged treatment courses and the emergence of drug resistant strains. 3, 4 Globally an estimated 500,000 deaths annually are attributable to influenza. 5 1 2 3 4 5 6 7 8 9 10 11 12 Title: Tuberculosis mortality: patient characteristics and causes", "Passage: Tuberculosis remains a serious public health issue worldwide. Even in the era of effective chemotherapy, TB still accounts for a substantial number of deaths annually. Early diagnosis is challenging, even in areas with abundant medical resources . In 2012, there were an estimated 12 million TB cases globally, including 8.6 million new cases, and 1.3 million fatal cases . The global case-fatality rates are reported to be between 7% and 35% , and risk factors for death may include noninfective comorbidities, human immunodeficiency virus infection and multidrug-resistant TB . Since the World Health Organization defined TB deaths as the number", "Title: Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis\nPassage: Patients commonly showing swelling of the affected jaw bones and the lymph nodes in the neck, and jaws are rapidly enlarged without tenderness . In the sporadic cases of this lymphoma, abdominal and pelvic organs are usually involved with the other abdominal and glandular tissues seen affected in some cases but to a lesser extent . Patients of BL are commonly presented to the Gastroenterology clinics with abdominal pain, ascites, abdominal distension and signs of intestinal obstruction. BL has also been observed to occur as a consequence of immunodeficiency, mostly in people with HIV/AIDS infections where it accounts for 30% Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case", "Passage: There is a substantial amount of evidence that HPAI H5N1 virus can infect extrapulmonary organ tissues 27] and precede other clinical manifestation . Our results presented that the viral antigens or viral RNA can be found in trachea, lung, brain, intestines, liver, spleen, lymph-node and kidney which were reported as same before , as well as in aortopulmonary vessel and ureter which were not reported before. Notably, the virus can be found in tissues of lower gastrointestinal tract including small intestine and large intestine but in stomach and duodenum. The origin of infection in the extrapulmonary organs could be blood-borne, Title: Pulmonary strongyloidiasis: assessment between manifestation and radiological findings in 16 severe strongyloidiasis cases", "Passage: There is much diversity among the manifestations of pulmonary strongyloidiasis. However, it is likely most patients present with one or more of the three most common complications; bacterial pneumonia, alveolar hemorrhage and allergic/eosinophilic manifestation from larvae . In patients with HS/DS, the number of larvae in the host is continuously multiplying . As this happens, many larvae pass through the alveolar membranes causing, sometimes, Abbreviations: HTLV-1 = human T-cell leukemia virus type 1, a mean was used for these values, b total 13 cases were tested serum albumin, c total 14 cases were tested HTLV-1 Acute exacerbation of interstitial pneumonia Title: Pulmonary strongyloidiasis: assessment between manifestation and radiological findings in 16 severe strongyloidiasis cases", "Passage: Meanwhile, fifteen of the sixteen cases had pulmonary manifestations . Acute respiratory distress syndrome was the most common manifestation , bacterial pneumonia and respiratory hemorrhage including pulmonary alveolar hemorrhage and hemoptysis followed. Acute respiratory failure was a common indication for pulmonary manifestations . In cases with bacterial pneumonia, pathogens detected were always enteric bacteria; 2 Klebsiella pneumoniae, 1 Escherichia coli, 1 Acinetobacter baumannii, 1 Citrobacter koseri .", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: CDC Summary 21 MAR 2020,\nPassage: Twenty-seven U.S. states are reporting some community spread of COVID-19. Title: CDC Summary 21 MAR 2020,", "Passage: More cases of COVID-19 are likely to be identified in the United States in the coming days, including more instances of community spread. CDC expects that widespread transmission of COVID-19 in the United States will occur. In the coming months, most of the U.S. population will be exposed to this virus. Title: CDC Summary 21 MAR 2020,\nPassage: All 50 states have reported cases of COVID-19 to CDC.", "Title: Focus on Translation Initiation of the HIV-1 mRNAs\nPassage: could also be involved in both mechanisms. This opened question has to be resolved. Title: Focus on Translation Initiation of the HIV-1 mRNAs\nPassage: alternative initiation mechanism that remains to be determined. Title: Lost in Translation (LiT)\nPassage: Drug discovery over the last 60 years has had cyclical ups and downs and has become accustomed to the great majority of projects failing. Almost all the major developments have been based on strong basic science, credible clinical evidence and advances in technology, but with single molecule targets. Many of the current major developments in basic and clinical science are based on applying very large data sets, GWAS, ENCODE, omics to complex pathways in biological control, disease aetiology and pathogenesis. The assumption is that many, perhaps most, of these will require multiple points of intervention, not single targets. Can translational Title: Lost in Translation (LiT)", "Passage: may be a pathway or a control system, not a single molecule. The concept that translational medicine starts when the pre-clinical teams offers a molecule for testing for the first time in human and ends when it is marketed as no longer appropriate. Translational medicine in the LiT3 era begins with the choice of target, not with FTIH and does not end until many years later when both physicians and patients have understood how to use it safely and effectively in the real world.", "Title: Chinese journals: a guide for epidemiologists\nPassage: In spite of this scepticism, the present author agrees with Smith that Chinese medical journals are \"a treasure house of medical science available for explorers\" provided that we evaluate the evidence published therein with no double standard. There are examples of reviews that cover Chinese journals and evaluate the evidence available, e.g. in a recent review on the effectiveness of hand-washing in preventing SARS, among the ten case-control studies identified, four were published in Chinese journals . Title: The potential contributions of traditional Chinese medicine to emergency medicine", "Passage: The first documented TCM monograph, Huangdi Nei Jing was written approximately between 770BCE and 200BCE. The main achievement of this book is that it establishes the basic theoretical framework of TCM such as: Zang Xiang Xue Shuo , Jing Qi Shen Xue Shuo , Yin Yang Wu Xing Xue Shuo , and Jing Luo Xue Shuo . Title: The potential contributions of traditional Chinese medicine to emergency medicine\nPassage: Wu De Zhuan Yi of naturalists to the theory of yin-yang and fi ve elements of TCM; and from Zhong Yong Zhi Dao of Confucianism to the harmony among Zang Fu , Qi-Blood and Yin-Yang of TCM. Building upon the TCM theory and knowledge in and before the Han dynasty, Shanghan Zabing Lun was written around 210AD by Zhang Zhongjing. Later, the book was divided into two books: one as Shanghan Lun , another as Jin Kui Yao Lue . Title: Chinese journals: a guide for epidemiologists", "Passage: of remarkable social and economic development unprecedented in China's modern history. However, rapid industrialization and urbanization are accompanied by many social problems, from the increasing rich-poor, urban-rural, coastal-interior disparity to heavy environmental pollution. Changes in disease profile with the increasing burden of non-communicable diseases as a result of an aging population with a successful one-child policy posed new challenges in the 21 st century . The SARS epidemic in 2003 exposed how a lack of transparency and delayed dissemination of information on the part of the Chinese government made an epidemic of then unknown aetiology a global problem .", "Title: Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy\nPassage: S pinal muscular atrophy is an inherited motor neuron disease and a leading genetic cause of infant mortality. It is characterized by the loss of lower motor neurons, which results in progressive atrophy of voluntary muscle groups leading to paralysis and eventually premature death . It is caused by the deletion of the survival motor neuron 1 gene in more than 95% of SMA patients . Humans have a second nearly identical copy of this gene, SMN2 . The majority of SMN2 transcripts lack exon 7 due to a translationally silent C-to-T transition +6 nucleotides within exon 7 . Skipping Title: Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells", "Passage: More recently, gene editing strategies mediated by ssODNs has been extended to iPSCs isolated from human skin fibroblasts of two patients affected by type I spinal muscular atrophy . SMA is an autosomal recessive genetic disorder caused by a genetic defect in the survival motor neuron 1 gene, which encodes SMN. Loss of SMN protein is thought to be responsible for the progressive loss of motor neurons which is paralleled by the progressive muscle wasting characteristic of SMA patients . Corti et al used a 75 bp ssODN was used to target and redirect splicing of the SMN2 gene, a Title: Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases", "Passage: DMD is caused by mutations in the largest known human gene called dystrophin , which spans 24 kbs of genomic DNA with its 79 exons . DMD encodes dystrophin, a 427 kDa protein localized on the cytoplasmic side of the sarcolemma of skeletal and cardiac muscle fibers as well as cortical/cerebellar synapses . Most common mutations are non-randomly distributed deletions that may span one or more exons . Surprisingly, the extent of the gene deletion does not correlate with the onset or severity of the clinical manifestations . Exonic duplications, missense, frameshift, point or intronic mutations account for the rest Title: Zika virus-induced acute myelitis and motor deficits in adult interferon \u03b1\u03b2/\u03b3 receptor knockout mice", "Passage: The fact that relative CMAP amplitude after spinal cord stimulation did not statistically correlate with VPS score suggests that damage upstream of spinal motor neurons may contribute to the hindlimb deficits. For example, CMAP amplitude was not reduced in two infected mice with overt paralysis . Paralysis in these animals could be caused by motor cortex, cerebellum, or brainstem dysfunction, as extensive infection was observed in these areas of the brain. While upper motor neuron disease is associated with rigid, rather than flaccid paralysis, we occasionally saw symptoms that could be interpreted as rigidity, such as walking with high haunches", "Title: Gain-of-Function Research: Ethical Analysis\nPassage: Beyond processes of deliberative democracy, furthermore, carefully designed social research will be important for shedding light on people's ultimate values, value weightings, levels of risk aversion, and risk-taking strategies etc. that policy should aim to reflect. Title: Gain-of-Function Research: Ethical Analysis\nPassage: were published in 2012. Advocates of these studies/publications argued that they would improve surveillance of H5N1 in nature and facilitate development of vaccines that might be needed to protect against pandemic strains of the virus. Critics questioned the validity of claims about such benefits and argued that the studies might facilitate creation of biological weapons agents that could kill millions, or possibly even billions, of people. Title: Gain-of-Function Research: Ethical Analysis\nPassage: at issue. Title: Gain-of-Function Research: Ethical Analysis", "Passage: at issue. Title: Gain-of-Function Research: Ethical Analysis\nPassage: Conceived as a scalar moral desideratum the point of this principle is that, in cases where the research poses serious risks, its evaluation should partly be based on the importance of the research question it aims to address. Some research questions are obviously more important than others. The more important any given target research question, the more ethically acceptable it would be to fund/conduct/publish a study posing a given magnitude of risk . The less important any given research question would be, the less ethically acceptable it would be to fund/conduct/publish a study posing the same magnitude of risk .", "Title: Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1\nPassage: grown to high titers, requires a low infectious dose, and contains multiple serotypes. Both the former Soviet Union and the United States previously weaponized the virus, producing large quantities for their now defunct offensive bioweapons programs . Currently, vaccine strain TC83 is used in horses and for high-risk personnel; however, due to the low rate of seroconversion achieved with this vaccine and its reliance on two single attenuating mutations , it is considered unfit for mass distribution . To date there are no FDA-approved therapeutics for VEEV infection, and further studies are required for clarification of the mechanisms associated with Title: Treatment of Neuroterrorism", "Passage: Venezuelan equine encephalitis virus is an alphavirus that is most commonly found in Central and South America. It is transmitted to humans by mosquitoes. In case of a bioterrorist attack, the distribution would be made through aerosols . The virus usually leads to an initial severe febrile illness in nearly everyone exposed at 1 to 6 days after exposure. Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas\nPassage: within the VEE subtype, subtype II Everglades virus , which is found only in Florida, can cause neurologic disease in humans and equids . Subtype IIIA, Mucambo virus, also causes febrile disease in humans . Title: Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus", "Passage: not formed. Viruses such as Venezuelan equine encephalitis virus can be used for production of EBOV antigen instead of structural proteins for the replicon vector. Thus, such vaccines are also quite safe . The gene inserted is typically GP, the main target of neutralizing antibodies. VRPs expressing EBOV VP24, VP30, VP35, and VP40 have been evaluated for their protective efficacy in a mouse model, but these were found not to be as protective as EBOV GP and NP antigens. VEEV replicons containing GPs from both EBOV and SUDV showed promising results in cynomolgus macaques after administration of a single dose.", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: During the 7 d preceding birth, no human mother has been reported to transmit the disease vertically. However, about 50% of newborns delivered while the mother was infected with CHIKV contracted the disease from their mother, despite the method of delivery. Furthermore, there have been instances of CHIKV transmission from mother to fetus causing congenital illness and fetal death . Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: According to Payne et al. , epidemiologic investigation of the 2012 MERS outbreak in Zarqa, Jordan, revealed that a 2nd trimester stillbirth had occurred as a result of maternal exposure to MERS-CoV. The mother experienced fever, fatigue, headache and cough, concurrently with vaginal bleeding and abdominal pain. On the 7th day of symptoms, she had a fetal death. The mother was confirmed to have antibody to MERS-CoV, and she self-reported having had unprotected contact with family members who later tested positive for the virus. This was the first documented occurrence of stillbirth during maternal infection with MERS-CoV. Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: MTCT of HIV-1 can occur during pregnancy , at delivery and via breastfeeding . HIV-1 can cross the placental barrier in utero either by microtransfusion or by transcytosis across the trophoblast cell layer . IP transmission may occur through direct contact between infant mucosa and HIV-1 infected maternal blood and/ or cervico-vaginal secretions . Finally, HIV-1 in breast milk may result in PP infection of the newborn through mucosal exposure . High maternal viral loads in serum and breast milk and low CD4 cell count as well as obstetric factors such as preterm delivery, vaginal delivery, and prolonged membrane rupture Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: And according to Dr. Paul Hunter, Professor of Medicine at the University of East Anglia , \"As far as I am aware there is currently no evidence that the novel coronavirus can be transmitted in the womb. When a baby is born vaginally it is exposed to the mother's gut microbiome, therefore if a baby does get infected with coronavirus a few days after birth we currently cannot tell if the baby was infected in the womb or during birth.\"", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: As at 09:00 on 21 February 2020, 47 confirmed cases of COVID-19 were reported in the WHO European Region and one of these cases had died . Data on 38 of these cases are included in this analysis. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: As at 09:00 on 21 February, few COVID-19 cases had been detected in Europe compared with Asia. However the situation is rapidly developing, with a large outbreak recently identified in northern Italy, with transmission in several municipalities and at least two deaths . As at 5 March 2020, there are 4,250 cases including 113 deaths reported among 38 countries in the WHO European region .", "Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy\nPassage: the present study showed significant decrease of anti-HIV-1 activity in the presence of patients' sera. Instead, the antiviral activity of AP3 increased in the presence of antisera from HIV-1-infected patients , suggesting that anti-HIV-1 antibodies actually enhanced the anti-HIV-1 activity of AP3, possibly because the binding of the antibodies to some sites in gp120 or gp41 promote the interaction of AP3 with viral gp41 NHR region. Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: the present study showed significant decrease of anti-HIV-1 activity in the presence of patients' sera. Instead, the antiviral activity of AP3 increased in the presence of antisera from HIV-1-infected patients , suggesting that anti-HIV-1 antibodies actually enhanced the anti-HIV-1 activity of AP3, possibly because the binding of the antibodies to some sites in gp120 or gp41 promote the interaction of AP3 with viral gp41 NHR region. Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: able to enhance the anti-HIV-1 activity of AP3. Our recent study has demonstrated that T20's anti-HIV-1 activity is enhanced by a non-neutralizing antibody directed against the NHR domain of the HIV-1 gp41 46 . We thus hypothesize that some of the anti-gp41 antibodies in HIV/AIDS patients may bind to a site in NHR domain adjacent to the AP3's binding region, resulting in increased interaction between AP3 and NHR-trimer and enhanced antiviral activity of AP3. Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: able to enhance the anti-HIV-1 activity of AP3. Our recent study has demonstrated that T20's anti-HIV-1 activity is enhanced by a non-neutralizing antibody directed against the NHR domain of the HIV-1 gp41 46 . We thus hypothesize that some of the anti-gp41 antibodies in HIV/AIDS patients may bind to a site in NHR domain adjacent to the AP3's binding region, resulting in increased interaction between AP3 and NHR-trimer and enhanced antiviral activity of AP3.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: While there is strong safety and efficacy data for use of NYVAC or MVA-vectored influenza vaccines, preexisting immunity remains a concern. Although the smallpox vaccination campaign has resulted in a population of poxvirus-na\u00ef ve people, the initiation of an MVA or NYVAC vaccination program for HIV, influenza or other pathogens will rapidly reduce this susceptible population. While there is significant interest in development of pox-vectored influenza virus vaccines, current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains. This would likely limit the use and/or efficacy of poxvirus-vectored influenza virus vaccines for regular and seasonal use Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Poxvirus vaccines have a long history and the notable hallmark of being responsible for eradication of smallpox. The termination of the smallpox virus vaccination program has resulted in a large population of poxvirus-na\u00ef ve individuals that provides the opportunity for the use of poxviruses as vectors without preexisting immunity concerns . Poxvirus-vectored vaccines were first proposed for use in 1982 with two reports of recombinant vaccinia viruses encoding and expressing functional thymidine kinase gene from herpes virus . Within a year, a vaccinia virus encoding the HA of an H2N2 virus was shown to express a functional HA protein and Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While poxvirus-vectored vaccines have not yet been approved for use in humans, there is a growing list of licensed poxvirus for veterinary use that include fowlpox-and canarypox-vectored vaccines for avian and equine influenza viruses, respectively . The fowlpox-vectored vaccine expressing the avian influenza virus HA antigen has the added benefit of providing protection against fowlpox infection. Currently, at least ten poxvirus-vectored vaccines have been licensed for veterinary use . These poxvirus vectors have the potential for use as vaccine vectors in humans, similar to the first use of cowpox for vaccination against smallpox . The availability of these non-human poxvirus Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose .", "Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: For the simulated daily number of cases , see Figure 1d , we found that \u03b5 i matched the observed daily number after 17 January 2020, but was significantly larger than the observations from 1 to 17 January 2020. This finding implied that under-reporting was likely to have occurred in the first half of January 2020. We estimated that the reporting rate after 17 January 2020 increased 21-fold compared to the situation from 1 to 17 January 2020 on average. One of the possible reasons was that the official diagnostic protocol was released by WHO on 17 January 2020 , Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: and the diagnosis and reporting efforts of 2019-nCoV infections probably increased. Thereafter, the daily number of newly reported cases started increasing rapidly after 17 January 2020, see Figure 1d . We conducted additional sensitivity analysis by varying the starting date of the under-reporting time window, e.g., 1 January 2020 in the main results, from 2 December 2019 to 3 January 2020, and we report our estimates largely hold. The exact value of the reporting rate was difficult to determine due to lack of serological surveillance data. The reporting rate can be determined if serological surveillance data are available for a Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: Under-reporting was likely to have occurred and resulted in 469 unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold compared with the situation from 1 to 17 January 2020 on average, and it should be considered in future investigation. We estimated the R 0 at 2019-nCoV to be 2.56 . Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: population; we would know who was infected and who was not , with high confidence. The reporting rate is the ratio of reported cases over the number of seropositive individuals. It was statistically evident that increasing in reporting was likely, and thus it should be considered in the future investigation of this outbreak.", "Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts\nPassage: When vaccines do not prevent infection or are not given, the last step in preventing morbidity and mortality in influenza is therapeutic treatment, of which antivirals are the current gold standard. The prevalence of antiviral drug resistance found in this and other studies is a warning that should not be ignored. Consistent with recent observations, all influenza viruses identified in this study were resistant to at least one class of antiviral. In this group of patients, 4% of viruses were resistant to both major classes of antivirals including some isolates of H3N2 and Apdm09. The majority of these viruses were Title: ICU-treated influenza A(H1N1) pdm09 infections more severe post pandemic than during 2009 pandemic: a retrospective analysis", "Passage: The benefits of antiviral treatment are controversial in the literature. A recent systematic analysis of influenza patients found only small benefits for either oseltamavir or zanamavir in the prophylaxis or treatment of influenza . However, they did not perform a subgroup analysis of neuraminidase inhibitor treatment of critically ill patients . Muthuri et al. reported that early versus later neuraminidase inhibitor treatment reduced the likelihood of mortality and the need for ventilator support in influenza patients with documented pneumonia . Our results, which suggest an association between early initiation of antiviral treatment and good outcome, support the active use of Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Treatment of severe influenza presents multiple challenges. The mainstay of therapy for patients with influenza is initiation of antiviral medication as soon as possible after illness onset . Currently available FDAapproved antiviral medications include neuraminidase inhibitors ; cap-dependent endonuclease inhibitor ; and adamantanes . NAIs and baloxavir have activity against both influenza A and B viruses. Adamantanes only have activity against influenza A viruses and are not recommended for treatment of influenza due to widespread resistance among currently circulating strains of seasonal influenza A viruses. Notably, FDA-approved antiviral medications for treatment of influenza are approved for early treatment of uncomplicated Title: Chloroquine is effective against influenza A virus in vitro but not in vivo", "Passage: Despite the availability of effective antiviral drugs, 1 influenza causes 3-5 million severe illnesses and 250 000-500 000 deaths in the industrialized world annually. 2 There are two classes of drugs currently licensed for use against influenza. The adamantanes, amantadine and rimantadine, target the M2 ion channel, and the neuraminidase inhibitors target the viral sialidase. The adamantane class of drugs has limited effectiveness against currently circulating strains of influenza due to the emergence of resistance. 3 Resistance to the NAIs is not as widespread but is becoming a concern in populations where use is frequent 4 and in the treatment", "Title: Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity\nPassage: The only positive sample to HPIV2 was collected during winter. HPIV1 and HPIV3 detection occurred mainly in late winter and spring. Similar results were reported showing this virus presence in samples collected in spring, autumn and winter. According to literature, HPIV3 are the most frequent viruses from this family, being type 1 and 2 viruses barely detected or even detected, which shows agreement with obtained results to literature data. Title: Laboratory epidemiology of respiratory viruses in a large children's hospital: A STROBE-compliant article", "Passage: viruses were more frequently detected in spring and winter, and RSV was more common in autumn. The variation pattern of influenza viruses was generally consistent. However, our study showed that RSV was more common in winter and spring, which was different from that reported in Saraya's study. Their study was conducted in adult patients with asthma, which might be responsible for the difference. In another study conducted from the year 2002 to 2014 involving 5102 samples, RSV was most frequently detected from December to March, influenza viruses from November to March, and HRV from December to June. Yang et al's Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Analyses showed that some viruses are possibly seasonal and were circulating during a specific period of the year. They are detected only in summer for Human Metapneumovirus, RSV A and B, and influenza Apdm09. For the latter, it is specific to the studied period since the influenza Apdm09 virus reappeared in R\u00e9union Island in October 2012 and was no longer circulating since late 2010. On the opposite, Parainfluenza 1,2 and 4 viruses were identified only in winter. For other pathogens, no specific period of detection was observed. Title: Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity\nPassage: This study was conducted at the Genomic Studies The total respiratory infections were detected mainly in winter, spring and summer of 2004, and autumn and winter of 2005, as showed in Figure 1A , which also demonstrate the seasonal distribution of the detected respiratory viruses.", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: Text: An outbreak of novel coronavirus disease has occurred on a cruise ship, the Diamond Princess . The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: total of 3711 persons , 199 symptomatic cases have been diagnosed on board as of 24 February, and additional asymptomatic infections and symptomatic cases after disembarkation have also been reported. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Date: 2020", "Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury\nPassage: Hepcidin is a \u03b2-defensin-like antimicrobial peptide that is mainly produced by the liver. Hepcidin not only shows antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and yeasts, but also functions as a principal iron regulatory hormone . Hepcidin binds to the iron export protein ferroportin and induces its internalization and degradation, which leads to decreased cellular iron export and increased intracellular iron retention . Because iron is an essential nutrient for all organisms, hepcidin also restricts the iron available to invading microbes, thereby enhancing the host defense against pathogens . Furthermore, hepcidin can modulate the lipopolysaccharide -induced acute inflammatory response via Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: Hepcidin is bound to plasma alpha-2 macroglobulin . Evidence suggests that other cells may express the hepcidin mRNA at a much lower level than the hepatocytes; the biological significance of the extra hepatic production of hepcidin remains uncertain. Plasma hepcidin is freely treated through glomeruli and in animals with normal kidney activity it quickly passes through the urine. In addition, a part of hepcidin is cleansed through degradation along with ferritin . Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: Hepcidin is effective on iron transfer from macrophages. In the presence of hepcidin, ferritin is transmitted into the macrophage and is destroyed by lysosomes, resulting in storage of iron inside the cell. In low concentrations of hepcidin, ferritin is present in the cell membrane, allowing the release of iron. After leaving the cell, iron oxide is rapidly oxidized by ceruloplasmin, a copper-rich ferroxidase and converted into ferric iron and then bound to transferrin . Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: the regulation of iron hemostasis. This peptide prevents iron absorption from the small intestine and releases iron from reticuloendothelial cells. In infectious diseases, macrophages and bacteria compete to absorb iron . Macrophages interfere with the absorption of iron by bacteria. Eventually, the pathogen does not grow and replenish. Factors that cause hepcidin production are increased in bone marrow and anemia. Other factors that increase the production of hepcidin are iron accumulation and inflammation .", "Title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression\nPassage: Prothrombinase Fgl2 belongs to the fibrinogen superfamily and is produced by activated macrophages or endothelial cells, transforming prothrombin directly into thrombin, so as to quickly initiate the process of coagulation. This promotes the conversion of fibrinogen into fibrin, resulting in thrombosis . Our study found that Fgl2 was highly expressed in peripheral blood mononuclear cells and in liver tissue of humans or mice with severe viral hepatitis, and was positively related to the severity of the disease . Gene therapy targeting Fgl2 silencing showed that the survival rate of fulminant hepatitis mice increased from 0 to 33.3% . Thus far, Title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression", "Passage: Prothrombinase Fgl2 belongs to the fibrinogen superfamily and is produced by activated macrophages or endothelial cells, transforming prothrombin directly into thrombin, so as to quickly initiate the process of coagulation. This promotes the conversion of fibrinogen into fibrin, resulting in thrombosis . Our study found that Fgl2 was highly expressed in peripheral blood mononuclear cells and in liver tissue of humans or mice with severe viral hepatitis, and was positively related to the severity of the disease . Gene therapy targeting Fgl2 silencing showed that the survival rate of fulminant hepatitis mice increased from 0 to 33.3% . Thus far, Title: Contact pathway of coagulation and inflammation", "Passage: human factor XII to this plasma restored the increase in VIIc. In FIX-deficient or FXI-deficient plasma, the stearateinduced increase in VIIc was greatly reduced, indicating that in the presence of contact surface the activation of contact system results in the activation of FVII . In another in vitro study in which a FXI-dependent effect on clot formation initiated by tissue factor, FXI increased prothrombin activation and the fibrin formation rate, revealing a role for factor XI in the propagation of clot growth after tissue factor-dependent initiation . Title: Contact pathway of coagulation and inflammation", "Passage: in the downregulation of fibrinolysis . In consistence with this hypothesis, systemic incorporation of anti-factor XI antibodies resulted in an almost twofold increase in endogenous fibrinolysis compared with a control antibody, indicating a novel role for the intrinsic pathway of coagulation . In a static in-vitro coagulation model in which clotting is initiated in recalcified citrated plasma by tissue factor coated on the bottom of microtiter plates, when larger clots were formed, FXI not only increased prothrombin activation and the fibrin formation rate but also inhibited fibrinolysis. Thus, in addition to enhancement of tissue factor-initiated coagulation, FXI inhibits fibrinolysis to", "Title: Estimating the number of infections and the impact of non-\nPassage: 2 Results Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: FLU003. Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: There were four potential limitations to our study. First, we only conducted a cross-sectional study in Study 3, whereas it would be preferable to measure Chikui likelihood earlier and then track the material and mental benefit of our participants years later. In the absence of a longitudinal study, our findings are suggestive but do not prove causality, and the following two questions therefore remain unaddressed: we are unable to confirm whether the correlation found in Study 2 means that it is the belief that boosts both financial and psychological well-being, rather than the reverse . Only a longitudinal study can", "Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus\nPassage: It has been shown that upon interacting with its receptor, CD40, CD40L induces profound effects on T cells, DCs, B cells, endothelial cells, as well as many cells of the hematopoietic and non-hematopoietic systems. Moreover, when CD40L engages CD40 on the surface of DCs, it promotes cytokine production, the induction of cell surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells , enabling DCs to mature and effectively induce the activation and differentiation of T cells. When CD40L engages CD40 on the surface of B cells, it promotes germinal center formation, immunoglobulin isotype switching, somatic hypermutation to Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: It has been shown that upon interacting with its receptor, CD40, CD40L induces profound effects on T cells, DCs, B cells, endothelial cells, as well as many cells of the hematopoietic and non-hematopoietic systems. Moreover, when CD40L engages CD40 on the surface of DCs, it promotes cytokine production, the induction of cell surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells , enabling DCs to mature and effectively induce the activation and differentiation of T cells. When CD40L engages CD40 on the surface of B cells, it promotes germinal center formation, immunoglobulin isotype switching, somatic hypermutation to Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells . In addition, CD11c is a DC integrin marker and upon stimulation, is down-regulated . Intracellular adhesion marker CD54, along with co-stimulatory markers CD40, CD80, and CD86 are all upregulated upon stimulation with CD40L . Moreover, mouse I-A d major histocompatibility complex is also up-regulated upon stimulation with CD40L . When our recombinant crCD40L was used to stimulate immature murine bone marrow DCs, we observed similar results to that when murine CD40L is used . CD11c was down regulated in both median flouresence intensity and the percentage of Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells . In addition, CD11c is a DC integrin marker and upon stimulation, is down-regulated . Intracellular adhesion marker CD54, along with co-stimulatory markers CD40, CD80, and CD86 are all upregulated upon stimulation with CD40L . Moreover, mouse I-A d major histocompatibility complex is also up-regulated upon stimulation with CD40L . When our recombinant crCD40L was used to stimulate immature murine bone marrow DCs, we observed similar results to that when murine CD40L is used . CD11c was down regulated in both median flouresence intensity and the percentage of", "Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: For the 143 HMPV genomes, we checked sequence conservation at transcriptional control regions, at the termini of each gene, as well as the lengths of intergenic sequences between gene boundaries. The length of the F-M2 intergenic region was different between group A and B viruses, that is, 13 nt and 2 nt, respectively. The SH-G and G-L intergenic regions were the longest, up to 125 nt and to 190 nt, respectively. Consensus nucleotides at the putative start and end regions flanking the ORF of the viral genes are shown in Fig. 1 . The gene-start and -end regions of N Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: For the 143 HMPV genomes, we checked sequence conservation at transcriptional control regions, at the termini of each gene, as well as the lengths of intergenic sequences between gene boundaries. The length of the F-M2 intergenic region was different between group A and B viruses, that is, 13 nt and 2 nt, respectively. The SH-G and G-L intergenic regions were the longest, up to 125 nt and to 190 nt, respectively. Consensus nucleotides at the putative start and end regions flanking the ORF of the viral genes are shown in Fig. 1 . The gene-start and -end regions of N Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: Sequence annotation of the full-length genomes using Geneious R8.1.5 identified the expected eight coding ORFs and non-coding genomic regions. The overall nucleotide identity between all 143 genome sequences analyzed was 58.2%. Nucleotide sequence identity was 71.3% within HMPV-A and 80% within HMPV-B. Intrasubgroup, A1, A2, B1 and B2 genomes shared 92.1% , 76.8% , 91% and 89.6% amino acid sequence identity. Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: Sequence annotation of the full-length genomes using Geneious R8.1.5 identified the expected eight coding ORFs and non-coding genomic regions. The overall nucleotide identity between all 143 genome sequences analyzed was 58.2%. Nucleotide sequence identity was 71.3% within HMPV-A and 80% within HMPV-B. Intrasubgroup, A1, A2, B1 and B2 genomes shared 92.1% , 76.8% , 91% and 89.6% amino acid sequence identity.", "Title: Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico\nPassage: Fifty randomly selected cases were asked to participate in the study from which 42 accepted participation. All approached controls agreed to participate. In total 126 individuals were recruited. Our drop-out rate was lower than 1% since one participant did not finish the follow-up due to the loss of the assigned GPS logger. Table 1 describes the main characteristics of the subjects in each group. No statistically significant differences were observed in most of variables except in age, since cases were significantly younger than the intradomestic or population controls . Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: We originally hoped to study T-cell cross-protection that might reduce symptom severity, but we also measured a variety of other parameters of pre-existing immunity . For statistical comparison of so many variables, we performed exploratory principal component and discriminant analyses. These analyses did not reveal any significant relationships of antibody or T-cell parameters at baseline with occurrence of pH1N1 infection or with symptom severity. Title: The Trojan Chicken Study, Minnesota\nPassage: This study was reviewed and approved by the University of Iowa's Institutional Review Board and Animal Use and Care Committee. The investigators participated in online human and animal subjects training. Informed consent was sought from participants before they were enrolled. Title: Examining the knowledge, attitudes and practices of domestic and international university students towards seasonal and pandemic influenza", "Passage: Students attending the main campus of the university were approached to participate in the study. Two methods were used to identify potential participants. Firstly, the interviewer directly approached a convenience sample of students who were located in the food halls and recreation areas of the university campus and invited them to participate. In the latter half of the study, a snowball approach was used. The snowball approach was adopted due to problems with identifying and recruiting postgraduate students. They constitute a considerably smaller percentage of the total student body, often are enrolled externally and attend classes in the late afternoon/evening.", "Title: Natural Killer Cells Promote Early CD8 T Cell Responses against Cytomegalovirus\nPassage: The development of antiviral immune responses involves the orchestration of a complex network of innate and adaptive immune cells to promote health over disease. Natural killer cells, plasmacytoid dendritic cells , CD11b and CD8a conventional dendritic cells , B cells, and CD8 T cells have all been demonstrated to be important for the generation of protective immunity to various viral infections . However, how the antiviral defense as a whole is coordinated, and in particular how the functions of different types of immune cells impact the shaping of the global immune response to viruses in vivo, is not thoroughly understood. Title: Natural Killer Cells Promote Early CD8 T Cell Responses against Cytomegalovirus", "Passage: To fight viral infections, vertebrates have developed a battery of innate and adaptive immune responses aimed at inhibiting viral replication or at killing infected cells. These responses include the early production of innate antiviral cytokines, especially interferons a and b , and the activation of cytotoxic lymphocytes such as the innate natural killer cells and the adaptive CD8 T cells. While critical for antiviral defense, cytokine or CD8 T cell responses can be detrimental or even fatal to the host when deregulated. Therefore, we need to better understand how the different arms of antiviral immunity are regulated. In particular, NK Title: Nanoparticle Vaccines Against Infectious Diseases", "Passage: cells including CD4 + helper T cells secrete different cytokines to modulate the functions of B cells, whereas CD8 + T cells recognize and destroy virally infected cells. Antibodies produced by the B cells can further neutralize the invading microbes or clear infected cell or opsonized pathogens through cell-mediated systems. APCs, in particular dendritic cells and macrophages, migrate through the body to sample, process and present the antigens to T-cells to activate cellular immune responses. These cells express various surface receptors to recognize cognate ligands and danger signals to trigger activation of different signaling pathways that eventually lead to the Title: Natural killer cells act as rheostats modulating anti-viral T cells", "Passage: As early as day 6 after medium-dose infection, the proportion and number of interferon-c 1 LCMV-specific CD8 T cells was increased two-to sixfold in mice depleted of NK cells , and antiviral T cells from these mice showed an enhanced ability to co-produce tumour necrosis factor . The number of LCMV epitope NP 396-404 tetramer-binding CD8 T cells in the spleen on day 5 p.i. was increased 4-to 20-fold in NK-cell-depleted mice relative to non-depleted control mice after infection with all doses of virus . The number of virus-specific IFN-c 1 CD4 T cells was also amplified 7-to 20-fold by", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's Title: Why language matters: insights and challenges in applying a social determination of health approach in a North-South collaborative research program", "Passage: A comparative analysis of the positive and negative effects of agro-ecological and conventional production systems is underway to consider policy options to promote health equity by ensuring that such factors are considered in food-related decision-making. There are extensive measurement challenges in doing this. Title: Australian public health policy in 2003 \u2013 2004\nPassage: the focus on high-visibility programs can demonstrate short-term economic returns. Title: Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis\nPassage: on the majority of questions to be rated as 'strong' overall . Greater emphasis was placed upon studies rated as 'strong' or 'moderate' overall within the findings of the review .", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: delivery of vaccine antigens due to their capability to induce robust T cell immune responses . Salmonella is one genus that has been well examined as a vector, building on the extensive research available on the micro-organism's physiology and pathogenesis . There exist several commercial vaccines that are used as anti-Salmonella vaccines in humans and animals . The general strategy for vectoring heterologous antigen is depicted in Fig. 1 . The first clinical trial of a recombinant, which was conducted over 20 years ago using an attenuated Salmonella as a delivery vector, led to the widespread testing of this bacterium Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Salmonella spp. is a Gram-negative bacterium that causes salmonellosis through orofecal routes. As a DNA vaccine carrier, S. enterica serovars Typhimurium is the most widely used Salmonella spp. . This bacterium is suitable for oral administration as its natural infection route. However, it can induce both mucosal and systemic immune responses, activating the humoral and cellular immune systems . As pathogenic bacteria, Salmonella spp. induce the immune response through their lipopolysaccharides and flagellin content on their surface that is recognized as pathogen-associated molecular patterns . Flagellin induces the immune response by binding with Toll-like receptor 5 , whereas LPS binds Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: To summarize, bacterial vectors such as Salmonella and viral vectors such as Ad show great promise as delivery vehicles for heterologous antigens; however, prior exposure to the vector must be considered. By judicious selection of the strain/serotype it will be possible to avoid the negative effects and it may indeed be possible to positively influence the response, particularly for humoral immunity. Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: Other bacteria that were developed as DNA vaccine carriers include Listeria monocytogenes , Shigella spp. , and Yersinia enterolica .", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Bat which causes the split of full length of orf8 into putative orf8a and orf8b, has been found in all SARS-CoV isolated from mid-and late-phase human patients . In addition, we have previously identified two bat SARS-related-CoV and proposed that the original SARS-CoV full-length orf8 is acquired from these two bat SARS-related-CoV . Since the SARS-CoV is the closest human pathogenic virus to the 2019-nCoV, we performed phylogenetic analysis and multiple alignments to investigate the orf8 amino acid sequences. The orf8 protein sequences used in the analysis derived from early phase SARS-CoV that includes full-length orf8 , the mid-and late-phase Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Orf8 orf8 is an accessory protein found in the Betacoronavirus lineage B coronaviruses. Human SARS-CoVs isolated from early-phase patients, all civet SARS-CoVs, and other bat SARS-related CoVs contain fulllength orf8 . However, a 29-nucleotide deletion, Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: SARS-CoV that includes the split orf8b , civet SARS-CoV , two bat SARS-related-CoV containing full-length orf8 , 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5 ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: infections and 800 deaths, and Middle East respiratory syndrome CoV which has caused a persistent epidemic in the Arabian Peninsula since 2012 . In both of these epidemics, these viruses have likely originated from bats and then jumped into another amplification mammalian host for SARS-CoV and the dromedary camel for MERS-CoV] before crossing species barriers to infect humans.", "Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections\nPassage: By prospective design, we mean that respondents are informed in advance of the day that they are requested to record their contacts. 6, 17, 32 In a retrospective design, respondents recall their contacts over a past time period without prior warning or instruction that they would be requested to do so. Of 64 surveys, 29 used a retrospective design and 26 used a prospective design. Only four surveys 6%) used both designs for the purpose of comparison. 10, 17, 50 For five surveys , it was not completely clear whether the study was prospective or retrospective. 20, 24, 30, 48 Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: Five surveys used an online respondent-driven method, which can be considered as a snowball or chain sampling technique. 31, 45, 60 Only one survey did not state information on sampling techniques. 34 Finally, three surveys conducted at the general population level used a convenience sample, 29, 44, 50 therefore not relying on a sampling frame. More details on the distribution of sampling schemes based on time and regions are presented in eFigure 3; http://links.lww.com/EDE/B552. Title: Tracking social contact networks with online respondent-driven detection: who recruits whom?", "Passage: After completion of the questionnaire, participants were referred to a research website that displayed the latest results . Participants recruited via the first panel who completed the survey had the opportunity to join a raffle for 1 of 10 gift cards of \u20ac25. This incentive only slightly increased peer recruitment as was shown in Stein et al. . For details on the software system and information on the 171 nonresponders we also refer the reader to Stein et al. . Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: The prospective design is subject to less recall bias than the retrospective design. This notion can be partly explained by the fact that respondents in the former are informed in advance about which days they will be assigned for reporting their contact information. Furthermore, they are also asked to keep a diary with them and finish reporting before the surveying day is elapsed. Thus, the prospective design requires more commitment from respondents. In return, a prospective design can obtain more reported contacts compared with retrospective design. 17, 50 However, large-scale studies are needed to further confirm these conclusions.", "Title: Efficacy of recombinant human soluble thrombomodulin for the treatment of acute exacerbation of idiopathic pulmonary fibrosis: a single arm, non-randomized prospective clinical trial\nPassage: From the data obtained in the historical untreated comparison group, the standard deviation of the P/F ratio in patients with AE-IPF was presumed to be 50 to estimate the target sample size. In addition, the effect size was also assumed to be 1.0 for the change in the P/F ratio 1 week after the initiation of rhTM administration. Thus, the minimum target sample size was calculated to be 10 patients with a two-sided alpha level of 0.05 and a power of 80 %. Title: Interplay between cost and effectiveness in influenza vaccine uptake: a vaccination game approach", "Passage: After each epidemic season, we estimate several groups by numerically calculating fluxes from one state to another. We mainly estimate nine fractions of individuals that are, QIV vaccinees and healthy-HV Q , QIV vaccinees but infected with influenza A virus-V Q I A , TIV vaccinees and healthy-HV T , TIV vaccinees but infected with influenza A virus-V T I A , successful free riders-SFR , failed free riders-FFR A or FFR B . Figure 1 . The layout of the whole dynamical set-up. The vaccine efficacy of TIV vaccine against influenza B virus is assumed e T , which Title: Interplay between cost and effectiveness in influenza vaccine uptake: a vaccination game approach", "Passage: maximum as the corresponding cost is higher; contrarily, TIV vaccinees are seen to reach the highest level for a mid-range of e T , although it starts decreasing with the further increase of e T that arises with the prevalence of free riders. Remarkably, the average payoff of society in case of different costs seems lower than that of the equal cost as the former case imposes a higher financial burden to society. Title: Interplay between cost and effectiveness in influenza vaccine uptake: a vaccination game approach", "Passage: vaccine, TIV vaccine or none-that evolve at the end of each season by imitating strategies based on the previous season's experience. We perform a series of numerical simulations by varying vaccination cost, vaccine effectiveness, transmission rates, etc., to depict different scenarios. Our results show that individuals are more inclined to take QIV vaccine whenever both vaccination costs are comparable; however, they prefer TIV vaccine if the cost difference gets higher. Notably, the framework has been validated by the so-called MAS approach.", "Title: Vaccination against Paediatric Respiratory Pathogens\nPassage: Acute respiratory infections remain one of the most common major public health threats, accounting for millions of episodes of severe acute lower respiratory infections that result in hospital admissions of otherwise healthy infants and young children worldwide . One-third of the annual deaths occurring in the world are thought to be due to infectious diseases, and respiratory tract infections are responsible for 4 million deaths worldwide each year . According to estimates made by the World Health Organization , pneumonia kills more children worldwide than any other disease, even more than acquired immune deficiency syndrome , malaria and measles combined Title: Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study", "Passage: common cause of significant morbidity, and occasionally mortality, in early childhood. Our current understanding of the epidemiology of early childhood infections is limited by reliance on community-based data from decades ago using low-sensitivity diagnostic methods, and recent studies that primarily focus on severe, hospital-managed disease. 10 11 Much of what we know, especially with newly discovered agents, originates from hospital-based prevalence studies where more than 80% of cases are less than 2 years of age, representing the sickest 2-3% of young children seen. Experience with influenza illustrates how easily disease burden can be underestimated by extrapolating from hospital data. Available Title: Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study", "Passage: For peer review only -http://bmjopen.bmj.com/site/about/guidelines.xhtml 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 and drinking water supplies, good personal hygiene standards, widespread vaccine use, and access to high quality medical care, infectious diseases remain the most common cause of significant morbidity, and occasionally mortality, in early childhood. Our current Title: Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study", "Passage: The highest incidence rates of acute respiratory infections are during the first two years of life where on average infants experience six to eight ARIs each year. 20 Complication rates from acute otitis media and sinusitis are also highest in this age group, 21 while three to five per cent of all infants are hospitalised for viral lower respiratory tract infections, including bronchiolitis, pneumonia, croup, and secondary bacterial pneumonia. 22 There is emerging evidence that infectious insults to the growing and developing lung during early childhood contribute to the pathogenesis of chronic pulmonary disorders in older children and adulthood, such", "Title: Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome\nPassage: The Syrian hamster has recently been used as an experimental rodent model for important infectious diseases including Ebola and other viral hemorrhagic fevers . For instance, Syrian hamsters infected with mouseadapted Ebola virus manifest many of the clinical and pathological findings observed in EBOV-infected non-human primates and humans, including systemic viral replication, suppression of the innate immune response, an uncontrolled inflammatory response, and disseminated intravascular coagulation syndrome . The Syrian hamster is emerging as a promising model for leishmaniasis and dyslipidaemia research . The Syrian hamster is also an important animal model in neurosciences research . For instance, this species Title: Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome", "Passage: The CHO cell genome is a useful tool for further improving the quality of our Syrian hamster transcriptome annotation for functional genomics work . CHO cells have been used in a variety of genetic, cell biology, and pharmacology studies. They also are the mammalian cell line of choice for producing large quantities of recombinant proteins in large amounts or in or industrial laboratory settings. Although Chinese and Syrian hamsters are phylogenetically distinct within the rodent subfamily Cricetinae , our data confirm that they are more closely related to one another as compared to other muroid rodents. Title: Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome", "Passage: The Syrian hamster is becoming an increasingly popular model for a variety of diseases, in particular, diseases known to infect non- Table 3 . Functional enrichment of the mouse genes mapped by our transcriptome assembly. human primates and humans. This Syrian hamster transcriptome discussed here represents a critical step forward in providing the tools necessary for advancing functional genomics in this important animal model. Title: Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome", "Passage: All hamsters were housed in individually ventilated cages . All hamsters are co-housed, unless scientifically justified and approved by the Institutional Animal Care and Use Committee or deemed necessary for veterinary reasons. Housing density is determined by the guidelines outlined in the Guide for the Care and Use of Laboratory Animals and the Association for the Assessment and Accreditation of the Laboratory Animal Care, International . Food and sterile or acidified water were provided ad libitum. Hamster diets were consist of pellets containing a variety of foods such as grains and dried vegetables along with some seeds. Water was provided", "Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study\nPassage: Information about pre-existing conditions was available for 20 case-patients. Four case-patients had no reported pre-existing conditions or risk factors for severe disease. Pre-existing conditions reported were: morbid obesity/obesity , lung disease , heart disease , pregnancy , diabetes , immunodeficiency , cerebral palsy , prematurity in an infant and genetic disorder . Three case-patients were reported to have more than one pre-existing condition/risk factor. Antiviral therapy was prescribed for 10 case-patients . Antibiotics were prescribed for 10 case-patients . Four case-patients received both antiviral and antibiotic therapy. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Data on pre-existing conditions were reported for seven cases; five had no pre-existing conditions while one was reported to be obese and one had pre-existing cardiac disease. No data on clinical signs e.g. dyspnea etc. were reported for any of the 38 cases. Title: Mortality, morbidity and health in developed societies: a review of data sources", "Passage: Studies based on health insurance data can relate to the onset of handicaps, hospital admissions, preventive dental care, etc. Administrative and billing data can be used to study, for example, social inequalities in health or differences in health status between regions. For example, in the USA, Medicare data can be used for comparative effectiveness research on treatments, benefit designs and delivery systems for Medicare beneficiaries , i.e. around 50 million people nationwide . These data permit, for example, national assessments of imaging utilisation and spending for this subpopulation. A French study has used healthcare consumption to compare the health status Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study", "Passage: the importance of pre-existing conditions such as heart disease and obesity is therefore not possible. Onset dates were estimated by reporting parties where information was not available. Finally, these data relate to a small number of cases.", "Title: Estimating the number of infections and the impact of non-\nPassage: current trends continue, there is reason for optimism. Title: Use of daily Internet search query data improves real-time projections of influenza epidemics\nPassage: posterior translates to a reduction in prediction uncertainty. We note that this improvement does not lead to more frequent prediction failure since for both weekly and daily data, the coverage for all targets remains above 90% . Title: Use of daily Internet search query data improves real-time projections of influenza epidemics\nPassage: associated with earlier availability of the Wikipedia data may still be important. Title: Use of daily Internet search query data improves real-time projections of influenza epidemics", "Passage: Much recent research activity has focused on short-and medium-term predictions of influenza activity and the importance of nowcasting 37] . While several previous studies have used similar indirect sources of influenza activity data for forecasting , none of these studies have used daily data or quantified the improvements associated with using these more readily available data sources. Other work has used data with a daily resolution as a basis for forecasting, but these studies have not evaluated the performance over several seasons and do not report gains in prediction performance associated with the higher resolution observation frequency.", "Title: Furin\u2010mediated protein processing in infectious diseases and cancer\nPassage: The prototypical and best-characterised member of the PCSK family is furin/PCSK3. Since it cleaves basic amino acid motifs, it has also been termed PACE . Furin is expressed by the FUR gene on chromosome 15. Although furin is ubiquitously expressed, its mRNA and protein levels vary depending on the cell type and tissue. High levels can be found in salivary glands, liver and bone marrow, whereas muscle cells express relatively low amounts of furin. 9 Three promoters , each harbouring an alternative transcription start site, have been described . However, the respective transcripts differ only in the first untranslated exon Title: Furin\u2010mediated protein processing in infectious diseases and cancer", "Passage: Furin is a member of the evolutionarily ancient family of proprotein convertases. Their similarity with bacterial subtilisin and yeast kexin proteases has coined the abbreviation PCSK . Humans encode nine members of this protease family , with PCSK3 representing furin . PCSKs are well known for their ability to activate other cellular proteins. The proteolytic conversion of inactive precursor proteins into bioactive molecules has already been described in the 1960s. 3 However, it took more than 20 years until furin was identified as the first mammalian proprotein convertase. 4, 5 To date, more than 200 cellular substrates of PCSKs have Title: Frontiers in antiviral therapy and immunotherapy", "Passage: Another mRNA under post-transcriptional regulation by Regnase-1 and Roquin is Furin, which encodes a conserved proprotein convertase crucial in human health and disease. Furin, along with other PCSK family members, is widely implicated in immune regulation, cancer and the entry, maturation or release of a broad array of evolutionarily diverse viruses including human papillomavirus , influenza , Ebola , dengue and human immunodeficiency virus . Here, Braun and Sauter review the roles of furin in these processes, as well as the history and future of furin-targeting therapeutics. 7 They also discuss their recent work revealing how two IFN-cinducible factors exhibit Title: Furin\u2010mediated protein processing in infectious diseases and cancer", "Passage: and are therefore predicted to express the same protein. 10 While the P1A and P1B promoters resemble those of constitutively expressed housekeeping genes, the P1 promoter binds the transcription factor C/EBPb and can be trans-activated upon cytokine stimulation. 10 In line with this, IFNc, TGFb, IL-12 and PMA induce furin expression. Upon translation of the mRNA, furin enters the secretory pathway as an inactive proenzyme and is integrated into the ER membrane via its Cterminal transmembrane domain . Like most type I transmembrane proteins, it harbours a short N-terminal signal peptide that is cleaved off cotranslationally. Similar to other proprotein", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: Rapid diagnostics plays an important role in disease and outbreak management. The fast and accurate diagnosis of a specific viral infection enables prompt and accurate public health surveillance, prevention and control measures. Local transmission and clusters can be prevented or delayed by isolation of laboratory-confirmed cases and their close contacts quarantined and monitored at home. Rapid diagnostic also facilitates other specific public health interventions such as closure of high-risk facilities and areas associated with the confirmed cases for prompt infection control and environmental decontamination . Title: The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care", "Passage: is clear that rapid identification of pathogens during other outbreaks facilitates rapid treatment and appropriate isolation of patients, leading to improved patient outcomes and potentially slowing the spread of infections such as influenza . Implementation of the first rapid diagnostic tests for influenza was directly associated with reduced length of hospital stay, decreased mortality, and reduced costs. 44 Access to diagnostic tests, early in the course of an outbreak and in hospital laboratories, has a positive public health impact. Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: Other studies have also reported that hospital admission numbers were significantly lower when rapid influenza virus testing was used in EDs. An analysis of outcomes for more than 300 adults at a tertiary care centre in New York found that early diagnosis of respiratory infections was associated with significantly fewer hospitalisations of influenza-positive patients. 7 In a small Irish study , the hospital admission rate for obstetric patients declined from 88% to 45% after on-site rapid influenza PCR testing was introduced. 10 The differences in clinical setting and patient group may explain the smaller decline in our study . Non-PCR-based Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: Conclusion: Rapid PCR testing of ED patients for influenza virus and RSV was associated with better outcomes on a range of indicators, suggesting benefits for patients and the health care system. A formal cost-benefit analysis should be undertaken.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Infectious MERS-CoV added to DC, goat or cow milk and stored at 4\u00b0C could be recovered at least 72 h later and, if stored at 22\u00b0C, recovery was possible for up to 48 h . MERS-CoV titre decreased somewhat when recovered from milk at 22\u00b0C but pasteurization completely ablated MERS-CoV infectivity . In a subsequent study, MERS-CoV RNA was identified in the milk, nasal secretion and faeces of DCs from Qatar . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Camel calving season occurs in the winter months and this may be a time when there is increased risk to humans of spill-over due to new infections among na\u00efve DC populations . What role maternal camel antibody might play in delaying infection of calves remains unknown . Juvenile DCs appear to host active infection more often than adult DCs and thus the sacrificial slaughter of DCs, which must be five years of age or older , may not be accompanied by significant risk of exposure to infection. In contrast to earlier results, slaughterhouse workers who kill both younger and older Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: is an animal of ritual significance after the Hajj pilgrimage . However, MERS-CoV infection frequency is reportedly much lower than is the widespread and frequent habit of eating, drinking and preparing DC products. Daily ingestion of fresh unpasteurized DC milk is common among the desert Bedouin and many others in the KSA. DC urine is also consumed or used for supposed health benefits. Despite camel butchery being a local occupation, neither butchers nor other at-risk groups are identifiable among MERS cases; this may simply be a reporting issue rather than an unexplainable absence of MERS. A small case-control study published Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: positive DC had been infected by a variant of the same virus, harbouring the same distinct pattern of nucleotide polymorphisms. All nine DC in the owner's herd, serially sampled, reacted in a recombinant S1 antigen ELISA, with the two animals that had been RT-rtPCR positive showing a small, verifiable rise in antibody titre . A rise in titre theoretically begins 10 to 21 days after DC infection . The authors suggested that the rise in titre in DC sera which occurred alongside a declining RNA load, while the patient was actively ill and hospitalized, indicated that the DCs were infected", "Title: The origins of the great pandemic\nPassage: In recent years, the question has arisen as to when and where the first case of the influenza pandemic of 1918 may have been detected. At least three locations have been mooted. First, the historian John Barry has suggested that Loring Miner, a physician in rural Kansas, in the USA, encountered cases in the early weeks of 1918 which, while akin to influenza, posed an unusual risk to life . Miner based his diagnosis on the symptomatology involved, and, interestingly, those symptoms did not include heliotrope cyanosis, which, as time drew on, came to be regarded as the tell-tale most Title: The origins of the great pandemic", "Passage: Kansas cases no doubt make for a compelling story, but one that has perhaps left a stronger-than-deserved impression that they were the very first cases. Moreover, the noteworthy influenza outbreak at Camp Funston, Kansas, in March 2018, was mild, with many cases but few deaths. This was after New York City already had evidence of very high influenza mortality and increased mortality in young adults . The virus causing those cases in New York City in February presumably predated the March outbreak at Camp Funston. So what happened on this army base in Kansas was not the first large outbreak Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America", "Passage: The first laboratory confirmed case in Victoria was notified on 20 May. Figure 1 shows notified cases by date of onset and location of acquisition until the commencement of the Modified Sustain phase; pandemic phase changes and case identification milestones are also indicated. Only 5% of the first 100 cases in Victoria were imported, and only eight of the 977 cases diagnosed prior to the introduction of the Modified Sustain phase reported a travel history. The first five diagnosed cases reported travel to the Americas: three brothers from one family returned from the US, a visitor from Mexico and another Title: The origins of the great pandemic", "Passage: closely associated with the pathogen involved, probably because some victims were asphyxiated by pus blocking their airways. Influenza was not a notifiable disease, but Miner, moved by the morbidity involved, sent off a report to the public health authorities . The significance of the incident, in Barry's view, lies in its timing and location. These deaths in rural Kansas took place in an area only a few hundred miles from a US Army Camp where, a few weeks later, Barry reports, one of the first recorded outbreaks of the pandemic may be said to have occurred.", "Title: Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak\nPassage: During the outbreak, the Municipal Health Service assessed the number of new cases from typical gastroenteritis symptoms self-reported by participants and staff. After the jamboree, participants and staff were given a questionnaire asking them to report to the Municipal Health Service whether gastroenteritis had developed within a week after departure. The questionnaire asked the date of symptom onset, symptoms, camp label, and hospital admission. Title: Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak", "Passage: On July 29 , the Municipal Health Service \"Hart voor Brabant\" in 's-Hertogenbosch provided advice on enhanced hygiene measures , instructed participants about proper hand hygiene and use of soap pumps and disposable paper towels, and assigned separate toilets for sick participants. In addition, the Municipal Health Service provided guidelines for cleaning toilets and contaminated surfaces with a 1,000-ppm chlorine solution. Sick participants were instructed to go to a fi rst aid tent. Sick participants were not allowed to prepare food until 3 days after their last symptoms. Persons working in the jamboree's fi eld hospital were instructed to wear Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3trimester and to test animals in petting zoos regularly for C. burnetii. Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: bioassay. The C. botulinum strains from 10 cases showed a common profile on fAFLP typing, thereby confirming a link to a common source. All had a recent history of injecting heroin which was obtained either in, or sourced, via Glasgow. The source of infection remains unconfirmed but is thought to be due to contaminated heroin, or cutting agent. There were four deaths, botulism contributing to two. Police Scotland was closely involved in risk management through increased drug seizures throughout the region, reducing the supply of potentially 'contaminated' heroin. Public health measures included; risk communication via distributing postcards widely to PWIDs", "Title: Age- and Sex-Specific Mortality Associated With the 1918\u20131919 Influenza Pandemic in Kentucky\nPassage: Although the antigenic recycling hypothesis is an attractive explanation of the low 1918-1919 pandemic excess mortality rates among older adults, it is a less parsimonious explanation for younger individuals. Distinct mortality profiles in different regions of the world point to the contribution of distinct factors leading to increased risk among young adults and to protection among seniors. Moreover, the rapid attenuation of the excess mortality risk among young adults by winter 1919 in Kentucky and Scandinavia and by subsequent seasons in New York City and Poland is consistent with a short time scale suggestive of the loss of a pool Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Using mortality data for 1917, we characterized baseline death levels using weekly death rates and a simple, cyclical, Serfling linear regression model . However, this initial attempt to characterize the baseline did not capture a small but noticeable summer mortality peak. To account for this variation, we modified the initial Serfling model with additional parameters, as was done in another study of the 1957 influenza pandemic in Maricopa County, Arizona . The added coefficients in the model account for time and seasonal variations in normal influenza activity, such that the oscillations may be written as: To account for uncertainty in Title: Age- and Sex-Specific Mortality Associated With the 1918\u20131919 Influenza Pandemic in Kentucky", "Passage: The atypically young age distribution of influenza-related deaths in the recent 2009 pandemic of influenza A virus subtype H1N1 infection was more reminiscent of the 1918-1919 pandemic than of later pandemics . Comparison of the age-based mortality risk profiles of the 2 pandemics, however, reveals substantial differences, most notably a peak among adults aged 50-64 years in 2009 . These differences lend further support to biological hypotheses that are unique to the 1918 virus and its historical context. Further comparisons of agebased mortality profiles across pandemics putatively associated with antigenic recycling would be interesting but would require mortality data stratified Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Although much progress has been made in uncovering the age-specific mortality patterns of this pandemic in several populations in Latin America , the United States, and Europe , more studies are needed to make sense of the heterogeneous death impact of this pandemic across different populations around the world. For instance, by characterizing and comparing the age-specific excess death rates across pandemic waves during 1918-1920 in different populations, researchers could suggest alternative hypotheses on the drivers of pandemic mortality risk at the time and place more emphasis on less-studied phenomena associated with the pandemic.", "Title: A multidimensional classification of public health activity in Australia\nPassage: Factors that influence health status and determine health differentials or health inequalities. They include, for example, natural, biological factors, such as age, sex and ethnicity; behaviour and lifestyles, such as smoking, alcohol consumption, diet and physical activity; physical and social factors, including employment and education, housing quality, the workplace and the wider urban and rural environment; and access to health care . Title: Viral factors in influenza pandemic risk assessment", "Passage: host factor or enhance its ability to repel a restriction factor . Recently a host factor, ANP32A, that differs between mammals and flighted birds was shown to be a cofactor of the influenza polymerase, and the species specific difference could explain the inefficient function of avian virus polymerase and the stringent selection for the 627Glu->Lys adaptive mutation in mammals . Title: Interrelationship between Climatic, Ecologic, Social, and Cultural Determinants Affecting Dengue Emergence and Transmission in Puerto Rico and Their Implications for Zika Response", "Passage: There are several limitations in this literature review. First, this review was not exhaustive as only extrinsic transmission factors were included in the analysis. Other factors, such as intrinsic factors pertaining to human immunity and the dengue virus , are important to consider in future studies. Second, there is an inherent risk of bias in the studies included in this review since only peer-reviewed studies were included . Third, there is also an inherit level of simplicity in the studies included as they investigated only one or two variables. Many of the included studies are limited by their design . Title: A multidimensional classification of public health activity in Australia", "Passage: Factors that influence health status and determine health differentials or health inequalities. They include, for example, natural, biological factors, such as age, sex and ethnicity; behaviour and lifestyles, such as smoking, alcohol consumption, diet and physical activity; the physical and social environment, including housing quality, the workplace and the wider urban and rural environment; and access to health care. 47", "Title: Antibiotic misuse in respiratory tract infections in children and adults\u2014a prospective, multicentre study (TAILORED Treatment)\nPassage: Between April 2014 and September 2016, a total of 616 patients with RTI were recruited . The panel diagnosed 516 patients as having a bacterial or a viral infection, encompassing 284 children and 232 adults . The expert panel diagnosed 12 adults as having a non-infectious disease . The reference standard diagnosis was inconclusive for 18 children and 70 adults. In 44% of the children with bacterial and viral RTI had comorbidity and not 'bacterial and viral RTI comorbiditis, most of them had mild diseases . In adults, comorbidity was seen more often and chronic diseases were more diverse . Title: Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012\u20132013: A PCR/Electrospray Ionization Mass Spectrometry Study", "Passage: During the 9-month study period, a total of 267 episodes of acute RTIs from 263 patients were recorded, including 96 episodes at a local clinic and 171 episodes at NCKUH . For convenience, each episode was counted as 1 case. Overall, 123 cases were male patients, and 152 , 60 , and 55 patients were 18 to 39, 40 to 59, and !60 years of age, respectively. Two-hundred and twelve patients presented with upper RTIs , and 55 cases presented with LRTIs. Compared with patients attending the local clinic, patients attending the medical care center were older and had more Title: Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012\u20132013: A PCR/Electrospray Ionization Mass Spectrometry Study", "Passage: To conduct a comprehensive epidemiologic study that included patients with and without comorbidity, we enrolled adults with acute RTIs within 7 days of onset who were treated at a local outpatient clinic of YC hospital or the outpatient or emergency departments of National Cheng-Kung University Hospital , a university-affiliated medical center in southern Taiwan, between October 2012 and June 2013. Acute RTI was defined as the simultaneous occurrence of at least 1 respiratory symptom or sign and at least 1 of the following symptoms: fever, chills, and cough. Lower RTI was defined as the presence of acute RTI and a Title: Antibiotic misuse in respiratory tract infections in children and adults\u2014a prospective, multicentre study (TAILORED Treatment)", "Passage: Patient recruitment for this prospective biomarker TTT-study took place in convenience and consecutive series at the ED and wards of secondary and tertiary hospitals in The Netherlands and Israel . For this subgroup analyses, paediatric patients and adult patients , with a suspected upper and/or lower RTI and a maximal disease duration of 8 days, were selected. RTI was defined as presence of two or more of the following signs: tachypnea, cough, nasal flaring, chest retractions, rales, expiratory wheeze and/or decreased breath sounds. For children, WHO age-specific criteria for tachypnea were used . Patients were excluded in case of: previous", "Title: The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort\nPassage: non-survivors were done by the Mann-Whitney U test. Breslow-Day's test was used to compare the performance of this cutoff value between the derivation and validation cohorts. A p value lower than 0.05 was considered statistically significant. All p values were twosided. Statistical analyses were performed using SPSS version 25.0 software. Title: Suffering a Loss Is Good Fortune: Myth or Reality?", "Passage: In the assessment of item discrimination, the discrimination index was computed by subtracting the mean score of participants in the lower group from the mean value of those in the upper group and dividing it by the maximum possible discrimination. A value of 0.19 or below indicated that the item was subject to improvement . Items with D < 0.19 included items 3, 4, 8, 13, 14, and 15. These six items were eliminated from the scale, thereby reducing the number of items from 24 to 18. Title: Interrelationship between Climatic, Ecologic, Social, and Cultural Determinants Affecting Dengue Emergence and Transmission in Puerto Rico and Their Implications for Zika Response", "Passage: Not Applicable because of the study design were disregarded. Each study was then given an overall quality score represented by the quintile range of the percentage of applicable Fink criteria answered in the affirmative. If the study satisfied 80-100% of applicable Fink criteria, it received a quality score of 5, satisfying between 60 and 79% resulting in a score of 4, those between 40 and 59% received a score of 3, those between 20 and 39% received a score of 2, and those between 0 and 19% received a score of 1. A score of 1-2 was considered fair; scores Title: Selection of key recommendations for quality indicators describing good quality outbreak response", "Passage: 8 or 9 and >70% of the experts scored in the top tertile, then the recommendation was marked as \"accepted\". If the recommendation had a median <8 and <70% scored in the top tertile, then the recommendation was marked as \"not accepted\" and was excluded. If the recommendation had a median <8 and >70% of the experts scored in the top tertile or the median was 8 or 9 and <70% of the experts scored in the top tertile, then the recommendation was marked as \"to be discussed\".", "Title: Multiplexed Nucleic Acid Programmable Protein Arrays\nPassage: These results indicate that M-NAPPA can be used for preliminary high throughput screening of novel protein-protein interactions. The screen can then be followed by a verification step using deconvoluted spots via NAPPA to identify the specific proteins that are involved. Title: Multiplexed Nucleic Acid Programmable Protein Arrays\nPassage: Third, we showed that M-NAPPA can be used in protein-protein interaction and serological screening studies. The results from M-NAPPA agreed strongly with those observed with non-multiplexed NAPPA . These data indicate that M-NAPPA presents a labor-and cost-effective strategy to initially screen for hits. Title: Evaluation of Targeted Next-Generation Sequencing for Detection of Bovine Pathogens in Clinical Samples", "Passage: the enteric and respiratory syndromes, for cases of E. coli infection, the PPA was 70% and the NPA was 100%, and for C. perfringens, the PPA was 56% and the NPA was 100%. For respiratory cases, the PPA for Mannheimia haemolytica was 78% and the NPA was 67%, and for Pasteurella multocida, the PPA was 71% and the NPA was 63%. The PPA for Histophilus somni was 100% and the NPA was 70%, and the PPA and NPA for Mycoplasma bovis were both 100%. Title: Multiplexed Nucleic Acid Programmable Protein Arrays", "Passage: To test whether M-NAPPA can be used to detect proteomic serological response, we screened ten serum samples from patients with type 1 diabetes that had been previously characterized using NAPPA arrays . A dozen hits were observed with M-NAPPA and NAPPA . Forty-nine of the 53 antigens identified by NAPPA were also detected by M-NAPPA. Four antigens, however, were detected with only one platform . These uncommon discrepancies may be due to variations in surface chemistry, plasmid concentration, printing or array processing.", "Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis\nPassage: In our patient, hemodynamic investigations using echocardiography and the PICCO system showed hypovolemia with low filling pressures and without any ventricular dysfunction. An elevated amount of extravascular lung water as well as an increased vascular permeability were also observed. This result is confirmed by the chest CT scan findings, showing a large amount of water in the alveoli, in the perivascular and in the pleural space. The pleural effusion was exudative and contained a high quantity of protein which can be explained by a protein leakage rather than by an inflammatory origin. Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis", "Passage: Under normal conditions, the endothelium plays the role of a selective permeable barrier to regulate plasma fluid exchange, as well as molecules and cells trafficking. Disruption of cell junctions, with combination of cell retraction process, lead to the loss of the vascular endothelium barrier function. In such conditions, fluids and proteins infusion are ineffective because of the immediate leakage to the interstitial space with a worsening of the respiratory failure without any efficacy on the hemodynamic state. This mechanism is similar to that reported by Clarkson in 1960 and is explained by a plasma leakage which was also described in Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis", "Passage: In our case, symptoms recorded at admission were compatible with acute infection by hantavirus and required admission to the ICU. The mechanism which may explain the severity of the disease is the tropism of hantavirus for the microvascular endothelial cell . This tropism causes microvascular hyperpermeability with fluid and proteins leakage leading to hypovolemia and to a non cardiogenic pulmonary oedema. Biologically, we observe an increased haematocrit level due to hemoconcentration, and a paradoxical reduced serum Fig. 1 Evolution of the serum protein and hematocrit levels during the first 14 days proteins level secondary to the transfer of proteins from Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis", "Passage: The pathogenesis of capillary leakage remains undefined. Some evidence suggest that hantavirus disease pathogenesis is immunologically mediated by cytotoxic T lymphocytes and other immune cells in target organs producing inflammatory cytokines. Overall, three hypotheses have been reported to explain the mechanism of increased capillary permeability involved in hantavirus infection: a) the attack of infected endothelial cells by virus-specific cytotoxic T lymphocytes , b) TNF-\u03b1 production by infected monocyte/macrophages and finally c) the direct effect of the virus on the endothelial cell functions . Bradykinin, a potent inflammatory and vasoactive nonapeptide generated by kallikrein at the sites of tissue injury is", "Title: Temporal trends in the discovery of human viruses\nPassage: is therefore of considerable interest. Title: Temporal trends in the discovery of human viruses\nPassage: M. E. J. Woolhouse et al. 2115 Title: Temporal trends in the discovery of human viruses\nPassage: We confirmed that our model reproduced the observed slight downward trend in the rate of discovery since 1954 and the observed variance in the data from 1954 to 2006 . The distribution of the number of virus species discovered per year shows slight overdispersion which falls within the predicted range . Together, these results support our choice of model, even though we do not explicitly consider heterogeneity in the probability of discovering a given species in any one year or temporal variation in sampling effort, detection techniques and reporting. Title: Temporal trends in the discovery of human viruses", "Passage: as analogous to constructing species discovery curves for any subdivision of geographical range or habitat. As we demonstrate below, this approach yields an excellent description of the discovery curve.", "Title: Nucleolus: the fascinating nuclear body\nPassage: processing suggests that processing complexes are at least to some extent maintained during mitosis. It is as yet unknown whether migration of the nucleolar processing proteins occurring at the onset of mitosis takes place as a consequence of the arrest of pre-rRNA synthesis or whether it is also regulated. Indeed, it is noticeable that during prophase, the components of the rRNA processing machinery appear to be delocalized before total repression of rDNA transcription occurs, and the most recently synthesized pre-rRNAs accumulate as partially processed 45S pre-rRNAs suggesting that total repression of pre-rRNA processing could occur prior to total repression of Title: Nucleolus: the fascinating nuclear body", "Passage: mitosis induces the Wrst events of nucleologenesis. Strikingly, Wbrillarin concentrates in PNBs and rDNA clusters when decrease in CDK1-cyclin B activity overcomes the mitotic repression of RNA pol I transcription , while Nop52 and other GC proteins are recruited later on transcription sites. This late recruitment is under the control of cyclin-dependent kinases since CDK inhibitors block this process . Thus, it seems that recruitment of the processing machinery at the time of nucleolar assembly is a regulated process most probably dependent on cell cycle progression. This provides a physiological situation to investigate the formation, control and dynamics of nuclear Title: Nucleolus: the fascinating nuclear body", "Passage: At the beginning of prophase, the components of the pre-rRNA processing machinery do not remain in the vicinity of the rDNAs but become partially distributed over the surface of all the chromosomes . The nucleolar proteins that relocate to the chromosome periphery are components of the DFC and GC of the active nucleolus. In living cells, nucleolar proteins tagged with GFP are concentrated around the chromosomes during mitosis and migrate with the chromosomes . However, the mechanisms maintaining interactions of nucleolar processing proteins with chromosomes during mitosis have not been characterized. The colocalization of the diVerent factors involved in pre-rRNA Title: Nucleolus: the fascinating nuclear body", "Passage: The dynamics of the processing nucleolar proteins was analyzed at the transition mitosis/interphase using rapid time-lapse video microscopy . The Wrst detectable assembly of proteins in foci occurred on the surface of the chromosome during telophase , followed by the progressive delivery of proteins to nucleoli ensured by progressive and sequential release of proteins from PNBs . Based on the observations of diVerent Wxed cells, it was concluded that the early processing proteins are recruited Wrst on transcription sites while the majority of the late processing proteins are still in PNBs . This sequence of events was conWrmed in living", "Title: The Model Repository of the Models of Infectious Disease Agent Study\nPassage: The premise of this tool is that researchers must be able to exchange and share their results. The development and broad acceptance of common model representation formats such as SBML is a crucial step in that direction, allowing researchers to exchange and build upon each other's work with greater ease and accuracy. Title: The Model Repository of the Models of Infectious Disease Agent Study", "Passage: The vaccine project is a single study project that uses a single influenza-based model of a medium-sized city in the United States. It was developed by the Emory Group headed by Ira Longini. The study consists of six runs generated from a single epidemiological model of disease spread. The main hypothesis behind the vaccine distribution study is to assess whether targeted antiviral prophylaxis , taken prophylactically, is effective in containing influenza. The authors conclude that TAP is nearly as effective as vaccinating 80% of the population, and further, that vaccinating 80% of children less than 19 years of age is Title: A Lattice Model for Influenza Spreading", "Passage: In the present model, we simply introduce some very basic rules of social distancing, which are over-imposed to the usual mobility rules during the epidemic. The upgrade of the model in order to include the effects of self-initiated behavioral changes will be discussed in a forthcoming paper. Title: Modelling and analysing the coexistence of dual dilemmas in the proactive vaccination game and retroactive treatment game in epidemic viral dynamics\nPassage: The remainder of this paper is organized as follows. The 'Methods and model' section introduces the new model of epidemic vaccination with the antiviral treatment model and demonstrates it schematically. The 'Results and discussion' section validates the proposed model in numerical simulations. Finally, the 'Conclusion' section summarizes and further discusses our findings.", "Title: Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease\nPassage: In addition to RNA Polymerase I, optimal rRNA gene transcription requires a number of accessory factors that facilitate Pol I recruitment, initiation, promoter escape, elongation, termination and re-initiation . Pol I transcription begins with the formation of the preinitiation complex by the upstream binding factor and the TBP-containing complex selectively factor at the rDNA promoter. SL-1 confers promoter sequence specificity by recognizing the core promoter element and it promotes a stable interaction between UBF and the rDNA promoter . In turn, UBF binds the upstream and core promoter elements as a dimer, possibly looping the intervening DNA into a nucleosome Title: Identification of MicroRNA-Like RNAs in Mycelial and Yeast Phases of the Thermal Dimorphic Fungus Penicillium marneffei", "Passage: protein. RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules involved in mitosis, while cytochrome P450 catalyses diverse reactions in fungal primary and secondary metabolism, and xenobiotic detoxification. As for PM-milR-M2, 20 potential targets were predicted, which include 13 transposon or transposable elements and seven conserved hypothetical proteins. Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: The out:in ratios were calculated by dividing the number of RPFs mapping within 5 leaders of a transcript by the number of RPFs mapping to the coding region of the transcript including the translation initiation codon . Read coverage was length normalized by nucleotide length of the respective feature . 5 leader:AUG ratios were calculated by dividing the number of RPFs mapping within the 5 leaders of a transcript by the number of RPFs mapping to the start codon of a transcript or non-canonical start codons. Read coverage was length normalized by nucleotide length of the respective feature. Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: The data provided by the TRPs will allow detailed characterization on the regulation of the translation of any single EBV gene or group of genes that frequently proved to be complex. The BMRF1 and BMRF2 transcripts that extensively overlap with each other and with BMRT3 and BMRT4 transcripts provide one example. BMRF1 and BMRF2 showed a similar number of reads in the TRP of cells treated with cycloheximide . However, the BMRF2 transcript recruited a much lower number of ribosomes than BMRF1 in cells treated with harringtonine . We could confirm by immunostaining that the BMRF2 protein is indeed expressed", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Key mechanisms governing resolution of lung inflammation", "Passage: Affecting approximately 10 % of UK adults, asthma is a common disorder of multi-factorial origins, with research indicating that both genetics and the environment have a significant role to play. In predisposed individuals, 'normal' environmental antigens transmigrate through the airway epithelia and are presented to na\u00efve T cells, which trigger activation of IgE production by B cells. IgE interacts with receptors on the surface of tissue resident mast cells, and further exposure to the antigen results in IgE cross-linkage with cell activation. The resultant mast cell degranulation causes release of mediators including histamine, LTB 4 , IL-8 and IL-10 and Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Respiratory viruses primarily infect and replicate within airway epithelial cells . During the replication process, the cells release antiviral factors and cytokines that alter local airway inflammation and airway niche . In a healthy airway, the inflammation normally leads to type 1 inflammatory responses consisting of activation of an antiviral state and infiltration of antiviral effector cells. This eventually results in the resolution of the inflammatory response and clearance of the viral infection . However, in a chronically inflamed airway, the responses against the virus may be impaired or aberrant, causing sustained inflammation and erroneous infiltration, resulting in the exacerbation", "Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines\nPassage: and to maintain self-tolerance . T lymphocyte activation culminates with the establishment of the immunological memory, providing the host with T cells more prone and efficient in responding to a reinfection by the same pathogen or upon tumor relapses . Besides, DCs are key players in humoral responses too. Indeed, they directly interact with B cells and indirectly support them by activating CD4 + T cells, leading to humoral memory. All these notions strengthen the idea that DCs represent an optimal target for immunotherapies and vaccines, acting at the interface of innate and adaptive immunity. Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines", "Passage: To address this purpose, it is becoming more and more evident that dendritic cells stand out as a potent tool in our hands, being the mediators of cellular and humoral responses . DCs have been discovered in 1973 by R. Steinman and Z. Cohn that divided phagocytic cells in macrophages and DCs on the basis of different effector functions: microbial scavenging activities for macrophages and antigen-presenting function for DCs . Since then, DCs have emerged as the most potent antigen-presenting cells capable of shaping adaptive responses both during infections and cancer. Moreover, the broad spectrum of DCs activation makes them Title: Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections", "Passage: . Interestingly, engagement of DCIR on pDCs increases their capacity to present antigen to T lymphocytes. Targeted delivery of vaccine antigens to mouse pDCs via coupling to an anti-SIGLECH antibody also promotes the induction of adaptive immune responses . Thus, the mechanisms that terminate the production of innate cytokines by pDCs during responses to viral type stimuli may not only be in place to prevent the development of a cytokine shock but also to switch pDC functions towards direct activation of adaptive immunity once their initial role in the orchestration of innate immune defenses has been fulfilled. Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines", "Passage: DCs educate CD4 + T cells against intracellular bacteria by promoting their polarization into IFN-\u03b3-producing Th type 1 cells. Upon infection by multicellular parasites, DCs, with the help of basophils, polarize CD4 + T cells into Th type 2 cells that produce mainly IL-4. For specialized mucosal and skin immunity, DCs drive the activation of Th type 17 . Thus, polarization of T cells is a crucial event that provides mechanisms specifically orchestrated to restore physiological homeostasis. DCs undergo apoptosis once they have fulfilled their functions. The rapid DC turnover after activation is necessary to avoid excessive T cell activation", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: CHIKV undertakes a complex replication cycle upon host infection , which makes its genome susceptible to mutations . For instance, Ae. aegypti, responsible for epidemics in Kenya, Comoros, and Seychelles, carried CHIKV with an alanine in the 226 position of the E1 gene . However, when the virus struck La Reunion Islands, a decline in population of Ae. aegypti, due to massive dichlorodiphenyltrichloroethane usage and dearth of Ae. albopictus species' www.plosntds.org population, resulted in an ecological pressure, favoring replacement of alanine at position 226 with valine . This mutation allowed CHIKV's secondary vector species, Ae. albopictus, to supplement Ae. aegypti Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: Within a year, the E1-A226V mutation was present in La Reunion Island, and Ae. albopictus apparently vectored the large epidemic infecting 34% of La Reunion Island's population . All of the CHIKV strains isolated from Mayotte carried the E1-A226V mutation, and the mutation was also found in Madagascar in 2007 . The E1-A226V mutation was not present at the beginning of the Indian Ocean Islands outbreak . However, more than 90% of later viral strains found there had incorporated the mutation , indicating a genotype switch during the winter season . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: The E1-A226V mutation also enabled an increase in infectivity of Ae. albopictus when compared to its infectivity of Ae. aegypti , and with several factors taken together, Ae. albopictus has become the new preferred and more lethal vector for CHIKV . In fact, Tsetsarkin et al. found that a Green Fluorescent Protein tagged E1-A226V virus was 100 times more infective to Ae. albopictus than it was to Ae. aegypti . In all the Indian Ocean Islands, Ae. albopictus became the main vector for CHIKV within 1-2 y after CHIKV was introduced to the region . Title: Dengue Fever, Hawaii, 2001\u20132002\nPassage: Ae. albopictus was the vector responsible for the 2001 Hawaii outbreak. Both entomologic surveys support that Ae. albopictus is ubiquitous, often common on all the islands, whereas Ae. aegypti is restricted to a few small foci on the relatively sparsely inhabited island of Hawaii.", "Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research\nPassage: research and requires that researchers reflect upon their own background and position, and how it will affect \"what they choose to investigate, the angle of investigation, the methods judged most adequate for this purpose, the findings considered most appropriate, and the framing and communication of conclusions\" :p483-4. This can entail, for instance, reflecting on how the researcher's status and role may have influenced what the informants disclose and how it is presented to the researcher . We found no explicit discussion of the primary study authors' background or position, including how their studies might have been influenced by these factors, Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust", "Passage: Academic researchers are to a great extent driven by the incentives of their profession, which reward publishing papers in peer-reviewed journals, regardless of whether or not the data are used to improve health outcomes. This necessarily influences the communication of results. High-level, multi-country comparisons have proven attractive to the editors of high-profile journals, The Lancet in particular . Publication in these journals in turn imbues academic estimates with a legitimacy that is not shared by data produced at the country level. Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research", "Passage: We regard this lack of information about and reflection on the context of the studies as a weakness in the studies and connect it to a lack of researcher reflexivity demonstrated by the primary study authors. The authors' contact information indicates that the majority of them held positions at medical faculties and that some of them were Ministry of Health employees. This suggests that they have approached their own study with a public health perspective, focusing on the achievement of herd immunity through patient compliance. The primary study authors' aim of increasing vaccine compliance appears to have influenced their recommendations Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: of homogeneity or assessment of similarity of results across studies was conducted and reported; 9) appropriate weighting of primary studies was conducted; and 10) the author's interpretation of the results were supported by the data . Each criterion is equally weighted and a final methodological score is tallied out of 10. Reviews with an overall rating of eight or more are considered strong, five to seven, moderate, and below four are considered to be weak in methodological quality.", "Title: Incubation periods of viral gastroenteritis: a systematic review\nPassage: and mean or median *Literature estimates show the range of incubation periods consistent with most published estimates and the most frequently stated central tendency for the incubation period; estimates that did not specify a type were assumed to be statements of central tendency. \u03c8Observational studies did not always report a defined number of participants, so a subject count is only reported for experimental studies. . Based on 2,540 observations from 20 observational studies and 15 observations from three experimental studies, we estimate the median incubation period for noroviruses to be 1.2 days with a dispersion of 1.64 . 5% of Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: a) The mean incubation period was 5.2 days : 4.1-7.0) . We set the same value of the incubation period and the latent period in this study. Thus, \u03c9 P = \u03c9' P = 0.1923. b) There is a mean 5-day delay from symptom onset to detection/hospitalization of a case . The duration from illness onset to first medical visit for the 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days . In our model, we set the infectious period of the cases as 5.8 days. Therefore, \u03b3 P = 0.1724. c) Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Sartwell and others have shown that the natural logarithm of incubation periods of acute infectious diseases tend to follow a normal distribution; hence the incubation period follows a log-normal distribution specified by the median incubation period and a dispersion factor . In a normal distribution, approximately twothirds of the data fall within one standard deviation of the mean; similarly in a log-normal distribution, approximately two-thirds of cases develop symptoms between median/dispersion and median \u00d7 dispersion. For each pathogen all observations were pooled together to form a single set of doubly interval censored observations; each data point contained a range of Title: The role of heterogeneity in contact timing and duration in network models of influenza spread in schools", "Passage: We assumed that symptom onset of infected individuals occurred later than shedding onset. Specifically, infected individuals entered a symptomatic state after a random, log-normally distributed incubation period with a mean of 1.52 days and a standard deviation of 0.66 . We correlated the latent and incubation period distributions, such that shedding began 0.5-1.2 days before symptom onset. However, under our assumptions for timevarying infectiousness, shedding amounts did not increase to an appreciable level until closer to the time of symptom onset.", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: 2 days . The mean duration from the first positive CXR to bilaterally multilobar lung infiltrates was 4.8 days . Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: 2 days . The mean duration from the first positive CXR to bilaterally multilobar lung infiltrates was 4.8 days . Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: CXRs revealed multiple bilateral lobar or segment consolidation in the lungs of all five patients, and radiographic lesions progressed rapidly after ICU admission . Three patients were examined by highresolution computed tomography . Unilateral or bilateral consolidations and infiltrates were found on HRCT scans of all three of these patients. Consolidations within a single lobe or several lobes with a clear border and air bronchogram were the most common findings on HRCT scans. Nodules, patches, pleural effusion, abscess and a cavity were also seen visualized by HRCT . The mean duration from onset to a single-lobe consolidation on CXRs was Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: CXRs revealed multiple bilateral lobar or segment consolidation in the lungs of all five patients, and radiographic lesions progressed rapidly after ICU admission . Three patients were examined by highresolution computed tomography . Unilateral or bilateral consolidations and infiltrates were found on HRCT scans of all three of these patients. Consolidations within a single lobe or several lobes with a clear border and air bronchogram were the most common findings on HRCT scans. Nodules, patches, pleural effusion, abscess and a cavity were also seen visualized by HRCT . The mean duration from onset to a single-lobe consolidation on CXRs was", "Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study\nPassage: Among the fatal cases, cough was the most commonly reported symptom . Other symptoms reported were fever , shortness of breath , muscle pain , headache , vomiting , runny nose , diarrhoea , sneezing and sore throat . Title: The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS)\nPassage: The most commonly reported symptoms among episodes of disease were respiratory , including coughing, sneezing/runny nose, sore throat and dyspnoea, in decreasing order. Other disease episodes included: fever , headache , body aches , and digestive disorders , including diarrhoea and vomiting/nausea. Title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study", "Passage: As shown in Figure 1 , more than half of the 18 H7N9-infected patients suffered from fever , cough , expectoration , fatigue , poor appetite , dry month , thirst , dyspnea , chest distress , and bitter taste in month . In addition, five patients suffered from hemoptysis and two suffered from dysphoria. Other symptoms such as muscle soreness , aversion to cold , perspiration , pharyngodynia , short breath , deep yellow urine , and cold-limbs also occurred in patients with H7N9 infection. Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: was collected by in-person interview. Participants were then instructed on the use of a daily diary to record the presence/severity of symptoms for 7 days following initial symptom onset. Symptom severity was rated on an ordinal scale from 0 to 3 . Symptom severity scores were quantified using the following five measures: individual symptom score for 20 symptoms, the upper respiratory symptom score, calculated as the sum of severity scores for earache, runny nose, sore throat, and sneezing, the lower respiratory symptom score, calculated as the sum of severity scores for cough, difficulty breathing, hoarseness, and chest discomfort, the gastrointestinal", "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: because cases currently being detected and reported would have mostly been infected in mid- to late-January. Average delays between infection and illness onset have been estimated at around 5\u20136 days, with an upper limit of around 11-14 days , and delays from illness onset to laboratory confirmation added a further 10 days on average . Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: cases currently being detected and reported would have mostly been infected in mid-to late-January. Average delays between infection and illness onset have been estimated at around 5-6 days, with an upper limit of around 11-14 days , and delays from illness onset to laboratory confirmation added a further 10 days on average . Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: hospitalization, and ultimately die. 22 Early predictions for incubation time are between 2 and 14 days, based on data from similar coronaviruses. The 14-day criterion for epidemiological risk assumes the longest estimated incubation time. 23 In addition, the World Health Organization has created its own interim case definition. 24 Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: profile online. 3, 4 Additionally, on January 28, 2020, an Australian laboratory reported growing the virus from a patient sample. As of January 30, 2020, there have been at least 9,776 persons infected and 213 verified deaths. 2 These numbers are likely underestimates due to the limited information available regarding incubation time, transmissibility, and virus origin. The What was the research question? Investigators adapted the \"Identify, Isolate, Inform\" Tool for use in suspected cases of 2019-nCoV.", "Title: The epidemiological and public health research response to 2009 pandemic influenza A(H1N1): experiences from Hong Kong\nPassage: The government subsequently ordered 3 million doses of pH1N1 vaccine for the local population of 7 million, and began distribution in December 2009. However, pH1N1 vaccine uptake was low, with <250 000 doses administered mainly to the elderly and healthcare workers. A subsequent longitudinal study found that intention to receive vaccine was an unreliable predictor of subsequent vaccine uptake. 44 Among healthcare workers, a study conducted in May 2009 found around 50% of survey respondents willing to receive pH1N1 vaccine. 45 Another study of community nurses in June 2009 found only 27% reporting willingness to receive pH1N1 vaccine. 40 Uptake Title: Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey", "Passage: with students, teachers were more likely to answer the above questions Table 3 and Table 4 ). Regarding the A/H1N1vaccination, 69.9% respondents believed that the occurrence rate of adverse reactions caused by A/H1N1 vaccination was fairly low and they were not afraid of taking up vaccination. Most residents thought that the state's vaccination strategy was reasonable. Title: Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey", "Passage: to the state's prior vaccination strategy for population at high risk such as students, teachers, healthcare workers and people with chronic disease, as well as the confusion between seasonal flu vaccine and A/H1N1 vaccine in residents. People who couldn't access the A/H1N1 vaccine may take up seasonal flu vaccine as preventive behaviors. The A/ H1N1 vaccine was not available in China until the middle of September 2009. All populations at high risk above three years old were invited for vaccination free of charge . A survey among 868 European travelers showed 14.2% participants were vaccinated against pandemic influenza A/H1N1 , Title: Pandemic (H1N1) 2009 among Quarantined Close Contacts, Beijing, People\u2019s Republic of China\nPassage: have worked to some extent at the beginning but were outpaced by local transmission ; the percentage of locally acquired infections ranged from <10% in June 2009 to >80% in September 2009 .", "Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain\nPassage: The 1918-1920 influenza pandemic, or the so-called Spanish flu, was responsible for more than 50 million deaths worldwide . In Europe, the excess mortality rate associated with the 1918-1919 influenza pandemic has been estimated at 1.1%, or approximately an 86% increase in all-cause mortality . This pandemic rapidly spread in a series of pandemic waves that gripped the world beginning in early 1918 . However, according to results of various phylogenetic and molecularclock analyses, the initial circulation of the virus from avian or swine and other mammal species to humans may have occurred a few years earlier . Moreover, the Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: . For instance, estimates of pandemic excess respiratory death rates have ranged from 6.1 per 10,000 for the Canary Islands to 169.7 per 10,000 for Burgos . Moreover, approximately 40% of between-province variation in cumulative excess death rates in Spain during 1918-1919 are explained by spatial factors, such as latitude, population density, and the proportion of children, have explained . However, in few of these analyses did researchers take into account a recrudescent wave in Spain, which peaked in Madrid in late December 1919 and in later months in the rest of Spain . Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: We retrieved all death certificates from the Madrid Civil Registry to construct time series of deaths during the 1918-1920 influenza pandemic . Each record provides specific details of the deceased, including the date of death, age, and causes of death. For years 1917-1920, the registry holds a total of 70,061 death records . Cause-of-death information for each death record allowed us to extract data on deaths attributed to influenza and respiratory causes. Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Spain experienced one of the highest excess mortality rates during the 1918 influenza pandemic in Europe , although this country did not take part in World War I. Perhaps this pandemic outcome is associated with the fact that Spain was going through a demographic transition and experiencing elevated death rates that were only comparable to those of eastern Europe. Of note, the life expectancy in Spain was 41 years in 1910 and 40 years in 1920 .", "Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses\nPassage: six individual IgG surfaces, five titrated concentrations of antigen in 2-fold dilutions were simultaneously injected in the horizontal direction. The binding interactions were monitored over a 10-min association period and a 45-min dissociation period using a high flow rate of 40 l/min. The last channel was injected with PBS/Tween/EDTA for reference subtraction. The surfaces were regenerated with two 18-s pulses of glycine, pH 1.5, at 100 l/min in both horizontal and vertical directions to allow the capture of different serum IgGs for kinetic binding measurements. Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: 90% at 6.5-7.5 min and finally to 0% at 8 -10 min. After chromatographic separation, the sample entered the Orbitrap Fusion TM mass spectrometer operated in positive electrospray ionization mode. The employed method included activated types of collision-induced dissociation and electron transfer dissociation when identifying control peptides, using a resolution of 120,000, a minimum signal of 5000, an isolation width of 3.0, and a normalized collision energy of 30.0 V. The S-lens radiofrequency level was set at 60%. For peptide identification, the data were collected in profile mode for the full MS scan and in centroid mode for the collision-induced Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: Deuterium Exchange-Using the H/D-X PAL TM robotic system , samples containing IgGs incubated with human IL-13 were added to a D 2 O-containing buffer, and the reactions were subsequently quenched at consistent times and temperatures using an automated sample run list. Two separate sample compartments were used for each experiment. One compartment was kept at 20\u00b0C for D 2 O labeling , and the other was maintained at 4\u00b0C for reaction quenching. After the samples were prepared, they were transferred into Chromacol screen top vials and stored in individual positions within the 4\u00b0C sample compartments. A work list was written Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: concentrations showed that the sensitivity of the method was \u03f331 ng of antigen-specific IgG per l of serum. This high sensitivity can facilitate the detection of less abundant IgGs exhibiting unique epitopes, maximizing the diversity of antibodies that can be recovered. After establishing the highly sensitive SPR and HDX LC/MS methods for detecting antigen-specific antibodies in serum, we tested their performance using sera from immunized mice. Nine serum samples collected from various strains of mice, which were immunized with human IL-13 using different protocols, were analyzed with these methods in a \"proof-of-concept\" study. These samples were previously classified as binders", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: An epithelial-centric alarmin pathway around IL-25, IL-33 and thymic stromal lymphopoietin , and their interaction with group 2 innate lymphoid cells has also recently been identified . IL-25, IL-33 and TSLP are type 2 inflammatory cytokines expressed by the epithelial cells upon injury to the epithelial barrier . ILC2s are a group of lymphoid cells lacking both B and T cell receptors but play a crucial role in secreting type 2 cytokines to perpetuate type 2 inflammation when activated . In the event of viral infection, cell death and injury to the epithelial barrier will also induce the expression of Title: Tight junctions in pulmonary epithelia during lung inflammation", "Passage: T H 2-high endotype is initiated directly via IL-25 and IL-33 released by epithelial cells or indirectly via stimulation of innate lymphocytes type 2 . A third initiation pathway acts via TSLP stimulation of dendritic cells, which attenuate T H 2 polarisation. Neither TSLP, IL33 nor IL23 impairs airway epithelial barrier . T H 2 and ILC2 cells recruit eosinophils, and, via induction of B cells, also mast cells and basophils. Thus, T H 2-high endotype is characterised by enrichment of eosinophils, basophils and mast cells . The accumulation of these immune cells results in a typical chemokine pattern, called Title: Tight junctions in pulmonary epithelia during lung inflammation", "Passage: factor and monocyte chemotractant protein 1 . The response to proteolytically active allergens involves storeoperated Ca 2+ entry in epithelial cells , and it should be noted that bacterial exotoxins also activate store-operated Ca 2+ entry . Other factors, which belong to dangerassociated molecular patterns , like adenosine , prostaglandin or histamine , initiate IL-1\u03b2, IL-6, IL-8 and GM-CSF production and release. Further, stimuli for chemokine release from airway epithelial cells are inhaled air pollutants and cold . More recent investigations revealed airway epithelial cells as a source of IL-25, IL-33 and thymic stromal lymphopoieitin . This subset of cytokines Title: Cytokines IL-17 and IL-22 in the host response to infection", "Passage: including those that encode proteins involved in tissue inflammation, immunosurveillance and homeostasis . By eliciting various innate defense mechanisms from epithelial cells, IL-22 is essential for host defense at mucosal surfaces against extracellular pathogens such as bacteria and yeast . In general, IL-22 acts to strengthen epithelial barrier functions and is involved in tissue homeostasis as well as in tissue repair and wound healing. However, excessive or prolonged production of IL-22 can cause pathology, such as psoriasis-like skin inflammation .", "Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings\nPassage: ASSUR calculated each plot were equally weighted and the average of these parameters were calculated for each target microbe. These averages were then pooled and re-averaged based on the sample type and also for all three sample types and these values used to rank developers in terms of ASSUR. Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings\nPassage: at the PATH laboratory and the Applied Biosystems 7500 Fast system at the CDC laboratory. Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings", "Passage: for each ASSUR radial data point were equally weighted and the averaged data within each plot was calculated as compared to optimal ASSUR plot values of 1.0 . The developers were ranked for each of the three sample panels and overall via the average of the pooled values for both targets per sample panel and for all six targets for overall. The developers were ranked in ascending order. The ranking of the developers based upon sensitivity and specificity only is provided in parentheses; FLU, influenza A, MTB, M. tuberculosis; SP, sputum; MS2, male specific bacteriophage; SPN, S. pneumoniae; BL, blood, Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings\nPassage: was tested in triplicate via the CDC real time RT-PCR protocols for the corresponding microbial NAs , and the C t values shared with the PATH laboratory for subsequent analyses.", "Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1\nPassage: Since MAPKs are activated by phosphorylation, dephosphorylation of MAPKs seems to be an efficient process to inactivate their activities. It can be achieved by specific protein kinase phosphatases which can remove the phosphate group from MAPKs. Examples of these phosphatases include tyrosine phosphatases, serine/threonine phosphatases, and dual-specificity phosphatases . Some DUSPs are also known as MAPK phosphatases . Currently, there are at least 10 MKPs identified, while MKP-1 is the most studied member of the family. The regulatory role of MKP-1 on cytokine induction is best demonstrated by MKP-1 knockout macrophages in response to lipopolysaccharide , a cell wall component Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1", "Passage: Since MAPKs are activated by phosphorylation, dephosphorylation of MAPKs seems to be an efficient process to inactivate their activities. It can be achieved by specific protein kinase phosphatases which can remove the phosphate group from MAPKs. Examples of these phosphatases include tyrosine phosphatases, serine/threonine phosphatases, and dual-specificity phosphatases . Some DUSPs are also known as MAPK phosphatases . Currently, there are at least 10 MKPs identified, while MKP-1 is the most studied member of the family. The regulatory role of MKP-1 on cytokine induction is best demonstrated by MKP-1 knockout macrophages in response to lipopolysaccharide , a cell wall component Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1", "Passage: Innate immune response protects the host from MTB infection by secretion of cytokines including TNF-\u03b1 in immune cells. Meanwhile, MAPK is one of the critical proteins in the regulation of immunity and cytokine expression. Since MAPK is regulated by MKP-1 in response to LPS and the activation of MAPK is important in BCGinduced cytokine expression, we hypothesize that MKP-1 plays a critical role in the immune regulation of BCG in human monocytes. We examined the involvement of MKP-1 in BCG-induced MAPK activation and its consequent cytokine expression. Here, we present evidences that MKP-1 plays an unexpected role in the regulation Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1", "Passage: Innate immune response protects the host from MTB infection by secretion of cytokines including TNF-\u03b1 in immune cells. Meanwhile, MAPK is one of the critical proteins in the regulation of immunity and cytokine expression. Since MAPK is regulated by MKP-1 in response to LPS and the activation of MAPK is important in BCGinduced cytokine expression, we hypothesize that MKP-1 plays a critical role in the immune regulation of BCG in human monocytes. We examined the involvement of MKP-1 in BCG-induced MAPK activation and its consequent cytokine expression. Here, we present evidences that MKP-1 plays an unexpected role in the regulation", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: All patients had HAdV-55 viremia. In four of the five patients, it was first detected in endotracheal aspirate samples. The time between initial ETA sample collection of adenoviruses and positive results for HAdV-55 nucleic acid in the blood was 1 to 10 days . Virus DNA copies in ETAs were determined for all patients during their ICU stay. The viral load was higher than 1 \u00d7 10 8 copies in three patients and 1 \u00d7 10 4 in one patient. The viral load became negative in the only patient who survived. In the four patients who did not survive, DNA Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: All patients had HAdV-55 viremia. In four of the five patients, it was first detected in endotracheal aspirate samples. The time between initial ETA sample collection of adenoviruses and positive results for HAdV-55 nucleic acid in the blood was 1 to 10 days . Virus DNA copies in ETAs were determined for all patients during their ICU stay. The viral load was higher than 1 \u00d7 10 8 copies in three patients and 1 \u00d7 10 4 in one patient. The viral load became negative in the only patient who survived. In the four patients who did not survive, DNA Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 \u00d7 10 copies in three patients and was Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: 1 \u00d7 10 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The", "Title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling\nPassage: Weekly respiratory virus identifications from September 1999 to August 2006 were obtained from the Respiratory Virus Detection Surveillance System , Public Health Agency of Canada . The RVDSS collects, collates, and reports weekly data from participating laboratories on the number of tests performed and the number of specimens confirmed positive for influenza, respiratory syncytial virus , para-influenza virus , and adenovirus. Specimens are generally submitted to laboratories by clinicians in the course of clinical care, and by clinicians participating in one of our national influenza surveillance programs, ). Indicators of influenza activity are reported year round on a weekly basis Title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling", "Passage: to the FluWatch program. The RVDSS is supplemented by case reports of influenza positive cases . From the case reports, influenza A was confirmed in all age groups and sporadic cases were confirmed in the off-season months of June through September. Infants and children under the age of 5 years accounted for 25% of the influenza A positive tests, and persons over the age 65 years another 35%. Unfortunately, FluWatch surveillance data does not provide the total number of tests by age. Testing practices are known to be varied . The predominant testing methods used for influenza detection varied considerably Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: In our study, leukocyte count was used as an indicator of inclusion criteria and it probably affected the positive rate. Viruses not considered in the study, for example coronaviruses, would underestimate the positive rate. Most studies showed that RSV or HRV was the most prevalent viruses in children with viral respiratory tract infection. 1 In this study, IAV was the most frequently detected respiratory virus, followed by RSV and HRV. IAV outbreak in 2009 could explain this shift. Data showed that about 60% of IAV infections were detected during the outbreak period. Studies showed that the H1N1 outbreak could change Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: Our study showed that RSV and HRV were the two most viruses involved in multiple infection, followed by IAV and PIVs, regardless of IAV infection in the H1N1 outbreak period. It was difficult to explain the variations of coinfection patterns based only on seasonal distribution. A recent study suggested that co-infection patterns were not random and certain pathogens had higher frequency of coinfection. 41 As molecular assays only detect nucleic acid and positive result does not mean the presence of the pathogen, when studying co-infection patterns of respiratory viruses, the ability to differentiate the real causative pathogens needs to be", "Title: Evolution of Genome Size and Complexity in the Rhabdoviridae\nPassage: Five of the novel viruses identified in this study were assigned to established genera. Two of these, KOOLV and YATV, clustered within the existing Ephemerovirus clade, and possessed the characteristic genome organization of ephemeroviruses, including a non-structural glycoprotein gene followed by a viroporin Newly proposed genera are indicated by a \u2020 symbol. Cytorhabdovirus, novirhabdovirus and nucleorhabdovirus outgroup sequences were excluded from the tree as they were too divergent to establish a reliable rooting. The tree is therefore rooted arbitrarily on one of two basal clades that comprise viruses isolated from mosquitoes. Title: Serious Invasive Saffold Virus Infections in Children, 2009", "Passage: During the past few years, intensive searches for new viruses, using conventional virologic methods and metagenomics, have resulted in the discovery of several new viruses. During the past decade, the family Picornaviridae has grown as the number of recognized genera has increased from 6 to 12 ; the numbers of species, types, and subtypes have increased even more. However, only viruses from 3 genera have been fi rmly established as being capable of causing clinically signifi cant disease in humans. Viruses from other genera have so far been detected only in noninvasively collected human sample material such as fecal and Title: Mimiviridae, Marseilleviridae, and virophages as emerging human pathogens causing healthcare-associated infections", "Passage: , , . In 2007, a first member of the Marseilleviridae family also related to NCLDVs, Acanthamoeba polyphaga marseillevirus , was isolated from water collected from a cooling tower in Paris, France, using a method based on Acanthamoeba polyphaga culture . This virus was named in honor of its amoebal host and of the name of the French city, Marseille, where it was discovered . The Marseillevirus was characterized by a 368-kb genome, 457 genes, and a minimum of 49 proteins . Furthermore, the first member of the second branch of Mimiviridae family, Cafeteria roenbergensis virus , was described in Title: Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts", "Passage: We also detected a sequence related to the large segment of members of the family Bunyaviridae in adult culicine mosquitoes. The contig contained a single long ORF that showed greatest similarity to members of the genus Phlebovirus, and the currently unclassified GOUV which was originally detected in specimens of the mosquito genera Anopheles , Culex and Uranotaenia in West Africa. Here, we provide evidence for a related novel virus from mosquitoes collected in France. Further field studies are necessary to allow the potential full isolation of this strain, which considering its divergence from GOUV, may constitute a novel genus within", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: NDV has also been explored as a vaccine vector for humans. Two NHP studies assessed the immunogenicity and efficacy of an rNDV expressing the HA or NA of A/Vietnam/1203/2004 . Intranasal and intratracheal delivery of the rNDV-HA or rNDV-NA vaccines induced both serum and mucosal antibody responses and protected from HPAIV challenge . NDV has limited clinical data; however, phase I and phase I/II clinical trials have shown that the NDV vector is well-tolerated, even at high doses delivered intravenously . While these results are promising, additional studies are needed to advance NDV as a human vaccine vector for influenza. Title: Viral vector-based influenza vaccines", "Passage: one single study, cross-reactive cellular immune responses against A viruses were observed after vaccination with a NDV-H5 construct. 168 The immunogenicity of recombinant NDV expressing the HA and NA genes of influenza virus A/Vietnam/1203/04 was tested in non-human primates. Both constructs induced VN and local IgA antibody responses and afforded protection from A challenge infection. 169, 170 Small numbers of clinical trials have been performed with NDV, which showed that the vector is well tolerated. Title: Viral vector-based influenza vaccines", "Passage: Newcastle disease virus is a single-stranded negative sense RNA paramyxovirus that causes disease in poultry. NDV has several favorable properties as a vaccine vector; no preexisting immunity in humans exists, NDV can easily be attenuated and reverse genetics systems to rescue recombinant NDV are in place. Thus far, NDV has been extensively characterized as an influenza vaccine vector in poultry, where it serves as a bivalent vaccine capable of inducing immunity against both NDV and influenza virus. As an added advantage, NDV is easily administered to poultry through nasal spray, drinking water or ocular drops. An overview of NDV-based influenza Title: Viral vector-based influenza vaccines", "Passage: The first study using NDV as a vaccine vector for influenza was NDV-H1, that expressed the HA gene of influenza virus A/ WSN/1933. Complete protection of mice against homologous challenge infection was achieved, demonstrating that NDV can be used as an influenza vaccine vector. 148 Consequently, a recombinant NDV expressing HA genes of A viruses has been licensed as a poultry vaccine in some countries and was shown to have a protective effect against challenge infection with A viruses in chickens and ducks in various studies. The NDV based A vaccine offered only partial cross-clade protection, but was immunogenic in", "Title: Recent developments in antiviral agents against enterovirus 71 infection\nPassage: A pseudosubstrate, LVLQTM peptide, could inhibit EV-71 infection through binding to the active site of 2A protease . Rupintrivir is an irreversible peptidomimetic inhibitor of human rhinovirus 3C protease, which reached phase 2 clinical trials with promising outcomes . Rupintrivir showed significant inhibition of EV-71 infection in vitro and in vivo but with reduced efficacy as compared with human rhinoviruses . X-ray crystallography of the complex of EV-71 3C protease with rupintrivir revealed that the half-closed S2 sub-site and the size reduced S1\u2032 pocket of EV-71 3C protease limits the access of the rupintrivir's P1\u2032 group which contains a lactam Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: A Protease inhibitor, rupintrivir thats prevents cleavage of viral proteins required for replication was tested in an HRV challenge trial. Rupintrivir was well tolerated and reduced viral loads and respiratory symptoms . However, in studies of natural infection, it did not significantly affect viral loads or symptom severity . Title: Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir", "Passage: is considerably lower than the values reported for favipiravir or galidesivir . The triphosphate form of remdesivir was shown to inhibit the RSV RdRp surrogate for EBOV RdRp . No significant inhibition was seen with human RNA Pol II and human mitochondrial RNA polymerase . The biochemical data obtained with purified recombinant RSV RdRp and a recent study with NiV RdRp point to delayed chain termination as a possible mechanism of action . Delayed chain termination refers to inhibition of RNA synthesis a few residues downstream of the incorporated inhibitor. However, the inhibition results have yet to be translated in Title: Epistatic Interactions within the Influenza A Virus Polymerase Complex Mediate Mutagen Resistance and Replication Fidelity", "Passage: suggests that inhibition of RdRp activity is the main mechanism of action for 5FU. As we did not identify mutations that mediate ribavirin or 5-azacytidine resistance, we cannot say whether mutagenic or nonmutagenic mechanisms are dominant for these drugs.", "Title: Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection\nPassage: Acute respiratory viral infections are among the most common reasons for patient visits in primary and acute care settings . Many viruses cause such acute respiratory illness including human rhinovirus , respiratory syncytial virus and influenza. These viruses can be associated with a range of clinical severity from asymptomatic to mild, self-limited illness to respiratory failure and death. Influenza alone causes 25 to 50 million infections annually in the USA, resulting in several hundred thousand hospitalizations and 20-40,000 deaths . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Another mechanism that viral infections may use to drive acute exacerbations is the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. Infection with a multitude of respiratory viruses causes disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells. For example, IFV infection was found to induce oncostatin M which causes tight junction opening . Similarly, RV and RSV infections usually cause tight junction opening which may also increase the infiltration rate of eosinophils and thus worsening Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: Human rhinoviruses usually cause mild acute respiratory infections, but on occasions can also cause more severe respiratory infections, including exacerbations of asthma and COPD. Of 115 Japanese children with asthma, a respiratory virus was detected in 86%, of which HRV or RSV were most common. 79 Ex vivo bronchial epithelial cells from people with asthma are more susceptible to HRV infection, due to deficient induction of IFN-b and IFN-lambda. In a study of 147 asthmatics on inhaled corticosteroid therapy, with a history of virusassociated exacerbations, patients were randomised to 14-day treatment with inhaled IFN-b or placebo within 24 hours of Title: Severe Acute Respiratory Infections With Influenza and Noninfluenza Respiratory Viruses: Yemen, 2011-2016", "Passage: Acute respiratory infections are a group of diseases that are caused by different microorganisms where viral etiologies are responsible for 80% of cases. 1 Influenza and noninfluenza viruses are responsible for significant annual morbidity and mortality across all age groups. 2 On average, influenza viruses infect 5% to 15% of the global population, resulting in 3 to 5 million cases of severe illness and between 260 000 and 650 000 deaths every year worldwide. The heaviest burden is among high-risk groups that include pregnant women, children under 59 months, the elderly, individuals with chronic medical conditions. 3 In 2015, it", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: provided input to the outline, multiple versions of the manuscript and gave approval to the final draft. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: 2 days to be hospitalised. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: As at 09:00 on 21 February, few COVID-19 cases had been detected in Europe compared with Asia. However the situation is rapidly developing, with a large outbreak recently identified in northern Italy, with transmission in several municipalities and at least two deaths . As at 5 March 2020, there are 4,250 cases including 113 deaths reported among 38 countries in the WHO European region . Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "Passage: As of 24 January 2020, the cumulative incidence in China is 830 cases, of which 549 cases were diagnosed in Hubei, 26 in Beijing, 20 in Shanghai, and 53 in Guangdong. Additionally, twenty-six deaths have been linked to the outbreak , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020. Considering that enhanced surveillance has been underway in these importing countries, case ascertainment has been perhaps better in exported case data.", "Title: Influenza A H1N1 2009 (Swine Flu) and Pregnancy\nPassage: The reluctance to be vaccinated is mainly due to worries about the side effects. Experience from the 2009/2010 pandemic confirmed the safety profile of the vaccine. Over 350 million doses of the vaccine were administered worldwide during the pandemic with no adverse long term effects noted in both the pregnant and non pregnant populations . Title: Travellers and influenza: risks and prevention", "Passage: with vaccination. During the H1N1 pandemic, influenza vaccines proved to be safe and effective for pregnant women and their unborn babies; findings very similar to studies of seasonal influenza vaccination in this high risk group. 67, 68 In line with these recommendations, the advice might be broadened to pregnant women travelling to influenza endemic areas and possibly to persons in close contact with pregnant women or other high-risk individuals, like partners and close family members ] or travel partners. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Maternal vaccination to prevent disease in the youngest infants has been shown to be effective for tetanus, influenza and pertussis . Influenza vaccination during pregnancy is safe, provides reasonable maternal protection against influenza, and also protects infants for a limited period from confirmed influenza infection and 50.4% in South Africa ). However as antibody levels drop sharply after birth, infant protection does not persist much beyond 8 weeks . Recently respiratory syncytial virus vaccination in pregnancy has been shown to be safe and immunogenic, and a phase-3 clinical trial of efficacy at preventing respiratory syncytial virus disease in infants is Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: The need to protect neonates and infants in the first 6 months of life from influenza is so important that many health authorities have recommended influenza vaccinations of pregnant women . Studies have shown that vaccination during pregnancy is effective in reducing influenza cases for at least one influenza season .", "Title: Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits\nPassage: In this study, the commonly identified viruses in patients with COPD exacerbations requiring ED visits were PIV3, Inf A virus, and human rhinovirus. This result was similar to the finding of Cameron et al from a study in Australia in which the most frequently detected viral etiologies were Inf A, PIV3, and rhinovirus. 21 In a recent review of eight studies, picornavirus was the most common virus in western countries and influenza virus was most common in Asia. 7 H. influenzae was the most common bacterial pathogen in COPD exacerbations in a previous study. 4 Pseudomonas aeruginosa and Klebsiella pneumoniae Title: Antiviral immunity is impaired in COPD patients with frequent exacerbations", "Passage: bacterial detection at exacerbation versus stable state, suggesting a causative role . Additionally, virus-induced secondary bacterial infection has been reported in both experimental and naturally occurring exacerbations . We have previously reported that experimental RV challenge in patients with COPD is associated with increased frequency of secondary bacterial infection compared with healthy subjects , an effect that is related to virus loads. Here, we extend these findings to reveal that frequent exacerbators have higher bacterial loads at 2 wk following onset of virus-associated exacerbation, suggesting that this subgroup of COPD patients might be at greatest risk of developing secondary bacterial Title: Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits", "Passage: Bacterial colonization and viral respiratory pathogens play important roles in exacerbations of chronic obstructive pulmonary disease , 1,2 especially in patients requiring hospitalization. 3 Viral and/or bacterial infections have been detected in up to 78% of patients with COPD exacerbations. 4 Although bacteria are considered the major cause of COPD exacerbations and antibiotics commonly used to treat exacerbations, 5 the importance of viral infections in COPD exacerbations was mentioned after the introduction and wide use of viral culture and real-time polymerase chain reaction . 6, 7 The link of viral infections to COPD has been emphasized in recent studies. COPD Title: Th17 profile in COPD exacerbations", "Passage: In the past, it was believed that only bacteria were capable of generating exacerbations in patients with COPD. 48, 52 However, the occurrence of these in the winter and symptoms similar to cold led to the belief that viruses were also associated with the complications of this obstructive pathology of the airways. 53 On the other hand, viral infections of the respiratory tract have been shown to influence the lung microbiome in patients with COPD, which indicates that both microorganisms can coexist and predispose to exacerbations. 54 The most prevalent viruses during acute exacerbations of COPD are rhinovirus, coronavirus, influenza,", "Title: Infection, Replication, and Transmission of Middle East Respiratory Syndrome Coronavirus in Alpacas\nPassage: A major question related to the pathogenesis of MERS-CoV infection in camels, and of great relevance to vaccination strategies, is whether animals that have been infected are resistant to reinfection and virus shedding and, if so, for how long. Our experimentally infected animals were completely protected against rechallenge 70 days later, which suggests that sterilizing immunity can be achieved. However, the animals that were infected through contact shed infectious virus after reinfection, albeit at much lower levels than infected control animals . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Some sero-assays have bypassed the risks of working with infectious virus by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins , or using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase . A pseudo particle neutralization assay has seen widespread used in animal studies and was at least as sensitive as the traditional microneutralization test. ] Studies using small sample numbers and ppNT found no evidence of MERS-CoV neutralizing antibody in sera from 158 children with LRT infections between May 2010 and May 2011, 110 sera from 19 to 52 year old male blood Title: Infection, Replication, and Transmission of Middle East Respiratory Syndrome Coronavirus in Alpacas", "Passage: quantities of virus . Serum was collected weekly and tested for neutralizing antibodies against MERS-CoV. All 3 experimentally infected animals had detectable levels of antibodies beginning on day 14 . Although infectious virus was isolated only from 2 of the 3 co-housed animals, these 3 animals had neutralizing antibodies detected first on day 21 or day 28 . Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: Various therapeutic options have been investigated for the treatment of MERS-CoV, but no therapy of proven value currently exists. The use of SC was associated with adverse outcome in SARS 69 and is not recommended for MERS-CoV. Many agents have shown inhibitory effects against MERS-CoV in cell culture including interferon +/\u00c0 ribavirin, cyclosporine A, mycophenolic acid, chloroquine and lopinavir. 70 Interferons, lopinavir, mycophenolate, possibly alisporivir and combinations are reasonable choices for testing in controlled clinical trials. Exploratory post hoc metaanalysis of studies related to SARS and severe influenza has shown a significant reduction in mortality following convalescent plasma treatment compared", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: The mouse-adapted SARS virus was generated by serial passage of an infectious wildtype SARS CoV clone in the respiratory tract of BALB/c mice. After 15 passages in mice, the SARS-CoV gained elevated replication and lung pathogenesis in aged mice , due to six coding genetic mutations associated with mouse adaptation. It is likely that MA15 is highly attenuated to replicate in human cells or patients due to the mouse adaptation. Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: aged mouse lungs, infection was attenuated, and less virus antigen was present in the airway epithelium as compared to SARS MA15, which causes lethal outcomes in aged mice . Title: Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice", "Passage: lung homogenates was highest for mice infected with the 6:2 Eng/09 virus on both day 2 and day 7 post infection. Day 2 lung titres were similar between the other three viruses. At the later time point two mice surviving in the 6:2 Tky/05 infected group had cleared the virus from the lung but did not regain weight . Title: Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice\nPassage: Six to eight week old BALB/c mice were infected with 10 4 or 10 5 PFU of either 6:2 Eng/09, or 6:2 Tky/05 virus intranasally. Two to three days post infection mice were culled; the lungs inflated with 1mL PBS, and placed in 4% PFA solution overnight. Lungs were embedded in paraffin, and mounted on slides by the Inflammation, Repair, and Development group, NHLI at Imperial College London.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Individual human case studies report long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms. In one instance, a HCW shed viral RNA for 42 days in the absence of disease . It is an area of high priority to better understand whether such cases are able to infect others. Over three quarters of MERS cases shed viral RNA in their LRT specimens for at least 30 days, while only 30 % of contacts were still shedding RNA in their URT specimens . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms. LRT samples are also best for attempting isolation of infectious virus, although the success of culture is reduced when disease persists . Recommended sample types include bronchoalveolar lavage , tracheal/tracheobronchial aspirate, pleural fluid and sputum . Fresh samples yield better diagnostic results than refrigerated material and if delays in testing of \u226572 h are likely, samples should be frozen at \u221270\u00b0C . If available, lung biopsy or autopsy tissues can also be tested . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The URT is a less invasive and more convenient sampling site however, and an oropharyngeal and throat swab or a nasopharyngeal aspirate/wash are recommended when URT sampling is to be conducted . Paired sera, collected two to three weeks apart are preferable for serological testing while a single sample is suggested to be sufficient if collected two weeks after onset of disease or a single serum collected during the first 10-12 days if conducting RT-rtPCR . Human urine and stool have been found to contain MERS-CoV RNA 12 to 26 days after symptom onset and are listed as samples that Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In the only study to examine the effect of sample type on molecular analysis, 64 nasopharyngeal aspirates , 30 tracheal aspirates, 13 sputa and three BAL were examined. The tracheal aspirates and BAL returned the highest viral load values followed by NPA and sputum. Unsurprisingly, higher viral loads generally paralleled whole genome sequencing and culture success and, in NPA testing, were significantly correlated with severe disease and death . This study demonstrated the importance of LRT sampling for whole genome sequencing.", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: \"I've certainly thought about how would we get food, or how much food did we have in the house, if we were to get quarantined.\" Title: Exposure science in an age of rapidly changing climate: challenges and opportunities", "Passage: Leisure activities and hobbies may be tapped to generate environmental monitoring data that can help describe the effects of climate change. As of 2011, there were 47 million bird-watchers in the US; 102 this group has been engaged by Project FeederWatch, a citizen science project sponsored by the Cornell Lab of Ornithology, to tally and report the number of each bird species they see in their yards for two consecutive days each week. They also enter weather data . For the 2014-2015 season, over 12,000 birders across the US and Canada submitted checklists . It would not be possible to Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: how the characteristics of the field change over time will be interesting to see. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: it might be worth considering how the proposed proximity data might relate to existing diary-based studies.", "Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion 5 . In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein 6 . Time-of-addition experiment confirmed that HCQ effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV-2, which was also found upon CQ treatment . To further explore the detailed mechanism of action of CQ and HCQ in inhibiting virus entry, co-localization of virions with early endosomes or endolysosomes was analyzed by immunofluorescence Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: of the two potential drugs, CQ appears to be the drug of choice for large-scale use due to its availability, proven safety record, and a relatively low cost. In light of the preliminary clinical data, CQ has been added to the list of trial drugs in the Guidelines for the Diagnosis and Treatment of COVID-19 published by National Health Commission of the People's Republic of China. CQ -N1,N1-diethyl-1,4pentanediamine) has long been used to treat malaria and amebiasis. However, Plasmodium falciparum developed widespread resistance to it, and with the development of new antimalarials, it has become a choice for the prophylaxis Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: and mechanisms of acting as a weak base and immunomodulator, it is easy to conjure up the idea that HCQ may be a potent candidate to treat infection by SARS-CoV-2. Actually, as of February 23, 2020, seven clinical trial registries were found in Chinese Clinical Trial Registry for using HCQ to treat COVID-19. Whether HCQ is as efficacious as CQ in treating SARS-CoV-2 infection still lacks the experimental evidence. Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: To this end, we evaluated the antiviral effect of HCQ against SARS-CoV-2 infection in comparison to CQ in vitro. First, the cytotoxicity of HCQ and CQ in African green monkey kidney VeroE6 cells was measured by standard CCK8 assay, and the result showed \u00a9 The Author 2020", "Title: Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine\nPassage: it is ''serum'' or ''blood''. Title: Serology in the Digital Age: Using Long Synthetic Peptides Created from Nucleic Acid Sequences as Antigens in Microarrays\nPassage: of the same patient serum as shown in , and for a blood donor serum. All dilutions refer to the 50 \u00b5L of diluted serum which together with the 50 \u00b5L bead panel had a final volume of 100 \u00b5L. Thus, final dilutions were two times higher than the ones mentioned in the figure. Title: Investigation of serum protein profiles in scrapie infected sheep by means of SELDI-TOF-MS and multivariate data analysis", "Passage: Serum samples used in this work were drawn every two weeks from six weeks post infection until euthanasia in 2007 for the longitudinal study . Serum samples at time of euthanasia from both 2006 and 2007 were used for the end-stage study . Serum samples were allowed to clot at room temperature for a minimum of 30 minutes and maximum 60 minutes, and then processed. Serum was pipetted in aliquots and frozen at minus 80 degrees within two hours of sampling. All the samples were subjected to the same handling procedures throughout the experiment. Title: Serology in the Digital Age: Using Long Synthetic Peptides Created from Nucleic Acid Sequences as Antigens in Microarrays", "Passage: A convalescent serum from a patient diagnosed with an uncertain filovirus infection was obtained with informed consent. Anonymous blood donor sera from the Uppsala Academic Hospital were used as negative controls. They were all used with informed consent according to the Swedish Biobank law which allows diagnostic patient samples to be used for similar purposes as the original sampling purpose.", "Title: Asthma in the elderly: what we know and what we have yet to know\nPassage: Whereas younger patients with asthma often suffer from allergic rhinitis complaints, elderly patients with asthma often suffer from sinus symptoms, including nasal obstruction, loss of smell and facial pain/headache. A recent Europe-wide epidemiologic study on the prevalence of chronic rhinosinusitis did confirm the well-known association between allergic rhinitis and early-onset asthma, but also demonstrated a clear increased risk to suffer from late-onset asthma in CRS patients . CRS may be phenotyped as CRS without and with nasal polyps , based on symptoms , nasal endoscopy and CT scanning. From those phenotypes, CRSwNP has a clearly increased risk of asthma comorbidity Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Additionally, in patients with asthma and patients with CRS with nasal polyp , viral infections such as RV and RSV promote a Type 2-biased immune response . This amplifies the basal type 2 inflammation resulting in a greater release of IL-4, IL-5, IL-13, RANTES and eotaxin and a further increase in eosinophilia, a key pathological driver of asthma and CRSwNP . Increased eosinophilia, in turn, worsens the classical symptoms of disease and may further lead to life-threatening conditions due to breathing difficulties. On the other hand, patients with COPD and patients with CRS without nasal polyp are more neutrophilic in Title: Asthma in the elderly: what we know and what we have yet to know", "Passage: With regard to this, recent evidence indicates the potential roles of chronic rhinosinusitis in the asthma pathogenesis. The GA2LEN surveys found that late-onset adult asthma was independently associated with CRS irrespective of nasal allergies . Recent endotype approaches suggest the specific roles of Staphylococcal enterotoxin sensitization in the pathogenesis of CRS subtypes with nasal polyp and severe late-onset non-atopic adult asthma . These findings may also be quite relevant to the elderly population, as elderly asthma is a considerably late-onset disease. Title: Asthma in the elderly: what we know and what we have yet to know\nPassage: in Caucasian populations , whereas CRSsNP does not significantly impact on asthma, but may be associated with other lower airway disease .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: abundantly in the microvascular endothelium. ANDV-infected hamsters fitted with physiologic monitoring devices exhibited diminished pulse pressures, tachycardia, and hypotension that appear to closely mimic the shock that is believed to be the proximate cause of demise in patients who succumb to HCPS . Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters", "Passage: Serial sections of lung tissue from these groups further revealed the presence of ANDV antigen colocalized to CD31-positive endothelial cells in both capillaries and larger vessels . Regardless of treatment, no differences were observed in the pathogenesis of HPS-like disease in ANDV-infected hamsters. Hamsters in all groups exhibited signs of mild to moderate inflam- mation, interstitial pneumonia, alveolar fibrin deposition, and edema characteristic of ANDV infection. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: The ANDV-Syrian hamster model has a number of features in common with the human disease, as well as some differences. Unlike the neurologic diseases that have been possible to elicit with HTNV, the hamster model for HCPS appears to be caused by capillary leak that results in pulmonary edema and the production of a pleural effusion with exudative characteristics. Typically the hamsters die between 11 and 14-d post-inoculation, reflecting a slightly accelerated incubation period in comparison to human infections. As with human HCPS, the microscopic examination of the lung reveals abundant fibrin deposition, thickened alveolar septa, and viral antigen expressed Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Compared to the human disease, ANDV-infected hamsters exhibit exceptionally high titers of live ANDV in their tissues, with much of the viral replication occurring in hepatocytes, which are spared in the human disease. Titers of live ANDV in some cases exceed 10 8 /g, whereas hantavirus isolates from human tissues have been notoriously difficult to obtain. Despite the universal occurrence of mildly-elevated hepatic enzymes in patients with HCPS, hepatic enzymes do not appear to be present at elevated levels in the blood of diseased hamsters even immediately before death .", "Title: Responding to the COVID-19 pandemic in complex humanitarian crises\nPassage: The Sphere Handbook, a collection of rights-based guidelines for humanitarian response, is the foremost authority on minimum standards for humanitarian assistance . However, despite the indisputable evidence for the efficacy of hand hygiene for reducing both bacterial and viral pathogen transmission, humanitarian WASH standards are based on evidence pertaining to the prevention of illnesses transmitted by the faecal-oral route, with the focus on hand hygiene proximate to latrines . And yet, latrines in crisis settings are often shared and distant from residential shelters, conferring a high risk of gender-based violence . Gender-based violence around latrines is an important deterrent for Title: The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks", "Passage: We then use the model to find the measures to keep R 0 v1. The necessary levels of latrine and bore hole coverages needed to eradicate the epidemic are both around 16 to 18%. Although the cost of construction of the required number of latrines is a one off cost, the benefits are large. Here we show what the benefits would have been in terms of protection against Hepatitis E. However, other diseases due to poor sanitation that have been reported in Uganda, such as cholera and dysentery, could be prevented in the same way . c Per capita rate Title: The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks", "Passage: Our model suggests that to eradicate the epidemic, the minimum number of additional latrines required is 3,47. The average cost of digging and constructing a basic pit latrine is approximately USD 250.00 Therefore, 3,477 would cost a total of USD 869,250.00. Thus, the cost per disability adjusted life year averted in Kitgum, in the case of Hepatitis E is 869,250/7,066 = USD 123.00. In addition to improving hygiene we should consider education. Let us now consider the case of education to the camp dwellers. Taking the simplest and cheapest scenario of hiring twenty guidance and counseling officials to educate the Title: The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks", "Passage: The number of latrines and boreholes that would have prevented the Hepatitis E outbreak in Kitgum are calculated using our results in preceding sections. First, it is assumed that if the people had the necessary and sufficient number of latrines in addition to safe drinking, then the outbreak would not have occurred. Then, the costs of constructing the required latrines and boreholes are computed. From the results, the cost of saving one life from Hepatitis E, for one year is determined.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: the percentage of confirmed cases among males to be 66%, compared with 34% among females .", "Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant\nPassage: RANBP2, a nuclear pore protein, has numerous roles in the cell cycle. RANBP2 is associated with microtubules and mitochondria suggesting roles in intracellular protein trafficking or energy maintenance and homeostasis of neuronal cells. RANBP2 mutations have been reported in acute necrotizing encephalopathy which could present with coma, convulsions, and encephalopathy. The hallmark of ANE is multiple, symmetric brain lesions located in the thalami bilaterally, putamina, deep periventricular white matter, cerebellum, and brainstem. It could be triggered by a viral infection in previously healthy children . Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: A gene panel targeting inflammatory disorders and post-infectious necrotic encephalopathies found a heterozygous RANBP2 missense mutation . This mutation has not been previously reported in the HGMD database. This variant has been observed at a frequency of <0.01% across the entire Broad ExAC dataset of individuals without severe childhood onset disease . Analysis of amino acid conservation indicates that the wild-type amino acid Lys1665 is conserved in 59 of 60 mammals examined, including 12 of 12 primates, and in 25 of 34 nonmammalian vertebrates increasing the likelihood that a change at this position might not be tolerated. In silico tools Title: Human core duplicon gene families: game changers or game players?", "Passage: The RANBP2 protein encoded by the progenitor gene is primarily localized within the periphery of the nuclear envelope and is thought to be required for cargo import and export . Hence, the RGPD gene family members may be modifiers of this function. Interestingly, RANBP2 was also shown to be involved in resistance against Simian Immunodeficiency Virus . It is thus possible that the expansion of RGPD genes is the result of an arms race between virus evolution and host resistance acquisition. The Ranbp2 knockout in mice is homozygous lethal. Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: Autosomal dominant mutations in RANBP2 have been associated with susceptibility to infectioninduced necrotizing encephalopathy . Previously healthy patients with pathogenic mutations in RANBP2 can present acutely with encephalopathy and convulsions in the context of an infection, with brain imaging revealing involvement of the brainstem, thalami, putamina, cerebellum and external capsules, and claustrum . Our patient has a similar presentation and imaging features as infection-induced necrotizing encephalopathy, including bilateral thalamic involvement. The rare heterozygous previously unreported variant we identified in RANBP2 affects a very conserved aminoacid and is predicted deleterious using in silico tools . It is possible that this variant", "Title: Salmonella enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks\nPassage: . Several studies have reported that many genes have been found to be associated with Salmonella resistance in the chicken . Title: Salmonella enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks\nPassage: niche that provides easy access for the pathogen to colonize with limited restriction . This factor alone makes young chickens highly susceptible to enteric bacterial infections, such as Salmonella, which can result in different degrees of disease spectrum from a subclinical carrier state to a high mortality rate depending on the infecting bacterial serovar and host's susceptibility. Title: Salmonella enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks", "Passage: Salmonella enterica subsp. enterica serovar Enteritidis is a zoonotic enteric pathogen that is most frequently associated with diarrheal disease in humans while chickens serve as asymptotic carrier . Consumption of contaminated eggs produced by infected layer hens is one of the leading causes of Salmonella food poisoning in humans . In chickens, S. Enteritidis can be easily transmitted horizontally via the fecal-oral route as well as vertically via the reproductive tract, which can contaminate the egg . Additionally, chickens can also harbor S. Enteritidis asymptomatically and persist throughout their lifespan, which makes the identification of infected chickens and the eradication Title: Salmonella enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks", "Passage: The impact of genetic background on the composition of chicken gut microbiota has been mostly investigated in broilers due to the association of intestinal microbiota with performance of broiler chickens in terms of feed conversion efficiency . Studies in broiler chickens have indeed shown evidence that host genotype had significant impact on shaping the composition of the gut microbiota . Few studies had explored the relationship between the host genotype and its influence on microbiota composition in layer chickens, especially related to disease resistance. The host genetic background plays an important role in the resistance and susceptibility to Salmonella infection", "Title: Viral factors in influenza pandemic risk assessment\nPassage: pandemic threat from a particular virus, because even if it gains efficient human-to-human transmissibility, its effective reproductive number and the proportion of the population at risk will be less than for a virus to which there is no cross-reaction in the population. For example, older individuals are thought to have been far less susceptible to pandemic H1N1 than were younger individuals, because they had previously been exposed to similar strains early in life . The low average age of infection with a swine variant form of H3N2 in North America is likely driven by reduced susceptibility in adults because of Title: Insights into the Evolution and Emergence of a Novel Infectious Disease", "Passage: For small host communities, the depletion of susceptible hosts can play a significant role in limiting an ongoing outbreak. What is the effect of a finite population size on these analytical results which assume an infinite host population? Figure 3A compares the simulated outbreak size distribution of different sized populations with our analytical predictions. Note that, for populations greater than 500, there is close agreement between numerical and analytical results. When considering populations of size 1,000 or more, we do not expect population size dependence to have a substantial effect. Title: Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence", "Passage: to the lack of sufficient host contact networks. This has resulted in a highly patchy distribution, characterized by sporadic and short-lived outbreaks in the United States, often confined to animal shelters , but a marked lack of sustained transmission in most dog populations that may be too small and sparse to support ongoing transmission. Hence, although a pathogen may possess all the mutations required to successfully infect a new host, whether it establishes itself is also dependent on the underlying population ecology. Interestingly, a new H3N2 CIV of avian origin has emerged in Asia and, more recently, in North America Title: Local risk perception enhances epidemic control", "Passage: Several studies suggest that immunizing or isolating interventions should target the most connected individuals in a population 52] . However, we rarely know the full contact network of a population. As proxies, we can target populations subgroups that tend to have high numbers of potentially disease-spreading contacts, such as young and school-aged children or health-care workers. We can also use biased sampling to identify highly connected individuals, such as the random acquaintance strategy in which random individuals are asked to name one of their social contact; individuals with more contacts are more likely to be named . In a sense,", "Title: Monitoring Influenza Epidemics in China with Search Query from Baidu\nPassage: area in that, the keyword selection and composition approach presented is more economical in terms of computational resources and cost compared to the original method by Ginsberg et al . Unlike the United States, in China alternative search engines such as Baidu are more widely used than Google. The market share of Google in China is less than 20%, while that for Baidu is more than 80% . The wide use of Baidu in China makes it a more representative search query source for this analysis. Title: A Multi-Method Approach to Curriculum Development for In-Service Training in China\u2019s Newly Established Health Emergency Response Offices", "Passage: The outbreak of severe acute respiratory syndrome in 2003 was a watershed moment for China . It triggered major health reforms and led to an increase in public health funding of about 100% by 2007, accounting for a rise in spending from 0.75% to 0.89% of the gross domestic product . Subsequent emergencies that echoed the imperative for reforms included the outbreaks of influenza H5N1 in birds and humans , melamine contamination of milk formula that affected over 294,000 Chinese children , and the earthquake in Sichuan that resulted in over 69 000 deaths, displaced about 15 million people and Title: Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey", "Passage: This study was performed in seven urban regions and two rural areas of China with over one million people in each region. Regarding the urban sites, Beijing as the capital of China locates in the northeast; Shanghai is a municipality in the east of China; Wuhan and Zhengzhou are both in the centre of China; Xi'an in the northwest of China is the provincial capital of Shanxi province; and Shenzhen of the Guangdong province is in the southeast of China. As for the rural sites, Jingzhou county and Zhengzhou county, from Hubei and Henan provinces, respectively, both locate in the Title: A Multi-Method Approach to Curriculum Development for In-Service Training in China\u2019s Newly Established Health Emergency Response Offices\nPassage: The proportion of the 1606 respondents who expressed a high level of need for these modules are shown in Table 3 .", "Title: Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability\nPassage: The indicated ZUFSP HALO-Tag fusion proteins were coupled to HALO Link beads and incubated with di-, tri-, tetra-, or penta-K63Ub. The last well shows competitive pull down with di-, tri-, tetra-and penta-Ub mixed together. Bound material was analysed as in . U2-OS/iGFP-ZUFSP *siR wild type or U2-OS/iGFP-ZUFSP *siR C360S cells were transfected with ZUFSP siRNA for 72 h with or without addition of doxycycline. Cells were fixed and processed for immunostaining with the indicated antibodies. Title: TRAF molecules in cell signaling and in human diseases", "Passage: in TLR3 signaling . In contrast, K48-linked polyubiquitination of Regulators of mRNA stability Tristetraprolin TRAF2 TNF-R1 Autophagy proteins Beclin 1 TRAF6 TLR4-, IL-1R-induced autophagy NDP52 TRAF6 TLR3-induced autophagy Regulators of ROS production ECSIT TRAF6 TLR1, 2, 4-induced ROS production TRAFs results in degradation of TRAF proteins by the 26S proteasome. K48-linked E3 ligases of TRAFs include cIAP1/2, Triad3A, AWP1, SOCS2, Siva-1, Numbl and CHIP. For example, upon viral infection, Triad3A is upregulated, and induces K48-linked ubiquitination and degradation of TRAF3, thereby forming a negative feedback loop to halt RIG-I signaling and type I IFN production . Thus, K48-linked ubiquitination and Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: promoted the dissociation of the 19S subunit from the 20S proteasome, followed by the distinct enrichment of the 19S-like complex in nuclear extracts together with the Tat-mediated recruitment of the 19S subunits to the HIV-1 promoter, which facilitated its transcriptional elongation . We also quantified UBA1 , the E3 ubiquitin-protein ligase UHRF1 , UBC and two Ubiquitinspecific-peptidases, USP30 and USP20 . Title: A Method to Identify p62's UBA Domain Interacting Proteins\nPassage: vitro ubiquitination . TRAF6 was chosen as an E3 in this in vitro ubiquitination assay due to its RING domain, a common feature of E3 ligases, and the observation that p62 is a scaffold for TRAF6 interaction . Therefore, in vitro ubiquitination assays using the E1-E2-E3 system were performed in the presence of either ubiquitin wild type or ubiquitin mutants . If one lysine mutant blocks the ubiquitination of HSP70, it would suggest that the ubiquitination of HSP70 utilizes that specific lysine linkage.", "Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: of a nose and throat swab as the gold standard. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: throat swab as the gold standard. See also 7. Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: A classic human study found that, in donors lacking neutralizing antibodies, pre-existing cytotoxic T-cell levels against influenza correlated with reduced virus shedding but not reduced symptoms after influenza virus challenge . Epidemiological studies of the 1957 pandemic, an H1N1 to H2N2 shift, suggested cross-protection, but these studies were too small for statistical significance or lacked laboratory confirmation of self-reported symptoms . A human challenge study found a correlation of CD4 memory with reduced illness duration, viral shedding, and symptom severity . Title: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends", "Passage: Correlations among influenza surveillance systems differed by influenza season. The correlation coefficient describing the association between Google Flu Trends and CDC Virus surveillance ranged from 0.67 during the 2003-04 influenza season to 0.94 during the 2004-05 influenza season . The mean correlation coefficient for these comparisons was 0.79 . The correlation between CDC ILI Surveillance and CDC Virus Surveillance ranged from 0.79 during the 2005-06 influenza season to 0.94 during the 2004-05 influenza season. The mean correlation coefficient for these comparisons was 0.86 .", "Title: Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane\u2010Associated Protein IFITM3 and Modified Variants\nPassage: The grey bands correspond to the mass of the different peptides found and to which part of the amino acid sequence it corresponds to. When the intensity of the MS signal was strong enough, MS/MS analysis was performed and is displayed by the red marks. The MS sequence coverage was greater than 95%. Title: Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates", "Passage: Within the primate sub-clade, three separate clusters of IFITM1, IFITM2, and IFITM3 were observed. The IFITM1 cluster contains the sequences from all analyzed primates, excluding marmoset and orangutan, and is located at the basal position of the primate sub-clade, indicating that IFITM1 separated earlier than other IR-IFITM genes, including IFITM2 and IFITM3, during the primate evolution. The IFITM2 and IFITM3 clusters only contain sequences from three hominids , indicating that IFITM2 and IFITM3 originated prior to the separation of these three hominids. Title: Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates", "Passage: Primate and rodent IFITM1, IFITM2 and IFITM3 have similar functions , but do not form a monophyletic cluster , indicating that they do not share the most recent common ancestor and moreover suggesting convergent evolution of IFITM1, IFITM2 and IFITM3 in primates and rodents. Convergently evolved amino acids between primates and rodents were found in the C-terminus of IFITM2 and IFITM3 , a crucial region for antiviral activity, supporting the association between viral infections and the evolution of IR-IFITM genes. Title: Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes", "Passage: Here our RNA-seq analysis of the ENA dataset shows that chIFITM1 basal expression levels are very low compared to chIFITM2 and chIFITM3. The analysis of the samples in presence of IFN\u03b1, H5N2, H5N1, H5N3, IBDV, IRF7, ALV, Lipopolysaccharide or in heat-stress induced conditions, also shows that higher expression levels can be observed for chIFITM3 and chIFITM2 suggesting a key role for these two proteins as antiviral IFITMs compared to chIFITM1, expression of which is only in the intestinal tract and in the testis. Although immunofluorescence staining seems to suggest that chIFITM2 is analogous to hIFITM1 the genome organisation supported by", "Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: could be affected by 2019-nCoV. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: We quickly identified the etiological agent, termed 2019-nCoV . The newly identified virus is an SARS-related virus but shares only 74.5% genome identity to SARS-CoV . We developed molecular detection tools based on viral spike genes. Our previous studies indicate that qPCR method can be used for the detection of 2019-nCoV in oral swabs or in bronchoalveolar lavage fluid . Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: can however be found in up to 30% ofpatients negative for influenza viruses . Chinese scientists in Wuhan, who had to deal with an increasing number of acute respiratory tract diseases resembling viral pneumonia, performed deep sequencing analysis from samples taken from the lower respiratory tract and found a \"novel\" coronavirus. The sequence of the complete genome was made public. At the same time, however, the notice from Wuhan brought to mind the SARS- and MERS-epidemics. The measures taken by the Chinese- and WHO-authorities are now well known. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: 9.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: Baculovirus has been extensively used to produce recombinant proteins. Recently, a baculovirus-derived recombinant HA vaccine was approved for human use and was first available for use in the United States for the 2013-2014 influenza season . Baculoviruses have also been explored as vaccine vectors. Baculoviruses have a number of advantages as vaccine vectors. The viruses have been extensively studied for protein expression and for pesticide use and so are readily manipulated. The vectors can accommodate large gene insertions, show limited cytopathic effect in mammalian cells, and have been shown to infect and express genes of interest in a spectrum of Title: Viral vector-based influenza vaccines", "Passage: Baculoviruses are extensively used as tool to express and produce influenza virus proteins. Currently, a recombinant HA protein vaccine produced in baculoviruses was approved for human use in the United States. However, baculoviruses have also been explored as live vaccine vectors. Since baculoviruses can readily be manipulated to express foreign antigens and can infect mammalian cells without causing cytopathic effect they are potentially promising vaccine vectors for influenza . 171 Initially, it was reported that vaccination with recombinant baculovirus expressing the HA gene of influenza virus could induce complete protection from homologous challenge infection. 172 Interestingly, in this study the Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is growing data on the potential use of baculovirus or pseudotyped baculovirus as a vaccine vector, efficacy data in mammalian animal models other than mice is lacking. There is also no data on the safety in humans, reducing enthusiasm for baculovirus as a vaccine vector for influenza at this time. Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines", "Passage: Besides the extra peace of mind that baculovirus-expressed vaccines have over inactivated vaccines, no large-scale bio-containments are required during the manufacturing of baculovirus-expressed vaccines, since baculovirus does not cause harm to human beings and its handling only requires biosafety class 1 practices . In contrast, large bio-containments are required for inactivated vaccine production, especially when handling the pathogens before and during the inactivation process. As no bio-containments or extra safety equipment are required, this would translate to a much lower production cost for baculovirus-expressed vaccines as compared to the cost of producing inactivated vaccines.", "Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919\nPassage: suppression of important antiviral immune responses . In addition, other influenza strains, such as fatal H5N1 infections in humans, have also been associated with the deleterious consequences of an excessive inflammatory response . Ultimately, the case fatality rate was so severe in young adults during the 1918-1919 pandemic that the average life expectancy rate in the US dropped by~12 years . Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: The 1918-1920 influenza pandemic, or the so-called Spanish flu, was responsible for more than 50 million deaths worldwide . In Europe, the excess mortality rate associated with the 1918-1919 influenza pandemic has been estimated at 1.1%, or approximately an 86% increase in all-cause mortality . This pandemic rapidly spread in a series of pandemic waves that gripped the world beginning in early 1918 . However, according to results of various phylogenetic and molecularclock analyses, the initial circulation of the virus from avian or swine and other mammal species to humans may have occurred a few years earlier . Moreover, the Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: Although mortality rates were low, the pandemic would ultimately claim between 500,000 and 2 million lives . In April 2009, the 2009-2010 swine flu pandemic, subtype H1N1, began with nearly simultaneous outbreaks in Mexico and the US, before spreading globally over the next 6 weeks. While the 2009-2010 pandemic had a low associated case fatality rate, resulting in 284,000 deaths worldwide, it had devastating effects on global economies and healthcare networks . Conventionally, influenza pandemics result in the extinction of previously circulating virus strains; however, this view was complicated by events in 1977. Although H1N1 was replaced by H2N2 as Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Spain experienced one of the highest excess mortality rates during the 1918 influenza pandemic in Europe , although this country did not take part in World War I. Perhaps this pandemic outcome is associated with the fact that Spain was going through a demographic transition and experiencing elevated death rates that were only comparable to those of eastern Europe. Of note, the life expectancy in Spain was 41 years in 1910 and 40 years in 1920 .", "Title: Host resilience to emerging coronaviruses\nPassage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Apart from the timely diagnosis of cases, the achievement of favorable clinical outcomes depends on the timely treatment administered. ACE2 has been reported to be the same cell entry receptor used by 2019-nCoV to infect humans as SARS-CoV . Hence, clinical similarity between the two viruses is expected, particularly in severe cases. In addition, most of those who have died from MERS-CoV, SARS-CoV and 2019-nCoV were advance in age and had underlying health conditions such as hypertension, diabetes or cardiovascular disease that compromised their immune systems . Coronaviruses have error-prone RNA-dependent RNA polymerases , which result in frequent mutations and Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The first viral isolate was patented and concerns were raised that this would restrict access to both the virus and to viral diagnostics . However, sensitive, validated reverse transcriptase real-time polymerase chain reaction -based diagnostics were quickly described and virus was made freely available subject to routine biosafety considerations . Subsequent epidemiology and research has identified the cell receptor as exopeptidase dipeptidyl peptidase 4 ; that MERS-CoV has a broad tropism, replicating better in some cells lines and eliciting a more proinflammatory response than SARS-CoV; is widespread in DCs; has the potential to infect other animals and that MERS kills", "Title: Discovery and Genomic Characterization of a Novel Bat Sapovirus with Unusual Genomic Features and Phylogenetic Position\nPassage: the seasonality of its detection or its host specificity. To address these limitations, long-term follow-up studies would be required to identify sufficient positive samples with associated clinical data. Increasing the scale of surveillance would also help, though there are practical geographical and logistic constraints in our locality. Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: The pathogenicity of these viruses is typically species-dependent, as is the severity of infection; they infect mainly their natural hosts and/or species that are closely related. Certain virus infections, however, can cross the species barrier, with the prime example being the zoonotic SARS-CoV, a novel coronavirus that is thought to have originated from bats before it adapted to its intermediate host, civet cats, and finally to humans . Bat colonies, which are scattered worldwide, are widely known to play host to a variety of coronaviral and adenoviral pathogens while acting as natural wildlife reservoirs of these viruses . Title: Finding and identifying the viral needle in the metagenomic haystack: trends and challenges", "Passage: approaches is overspecificity, which makes classification of unknown sequences problematic. This limitation can be particularly acute given the known very high intraspecific variability existing in some viral species or higher order taxa. For example, current criteria of the International Committee for the taxonomy of viruses tolerate up to 28% of nucleotide sequence divergence for the polymerase or capsid protein genes for isolates of a same species in the Betaflexiviridae family and a similar level of divergence at the whole genome level in the Potyviridae family . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The first open reading frames have become a key diagnostic and taxonomic target for CoV species identification. With less than 80 % identity between the amino acid sequence of MERS ORF 1ab and betacoronavirus relatives, Tylonycteris bat HKU4 and Pipistrellus bat HKU5, it can be concluded that it is a novel and distinct virus. MERS-CoV is predicted to encode ten open reading frames with 5' and 3' untranslated regions . The structural proteins include the spike , envelope , membrane and nucleocapsid . The products of ORF1a and ORF1b are predicted to encode nonstructural proteins.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In humans, overt disease was given the name Middle East respiratory syndrome, with the acronym MERS. From intermittent animal-to-human spill-over events, the MERS-CoV spreads sporadically among people, causing more severe disease among older adults, especially males, with pre-existing diseases. The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Qatar for care . The new virus was initially called novel coronavirus and subsequentlty entitled the Middle East respiratoy syndrome coronavirus . As of 2 nd of September 2015, there have been 1,493 detections of viral RNA or virus-specific antibodies across 26 countries confirmed by the World Health Organization , with over a third of the positive people dying . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity . Title: CDC Summary 21 MAR 2020,\nPassage: COVID-19 is caused by a coronavirus. Coronaviruses are a large family of viruses that are common in people and many different species of animals, including camels, cattle, cats, and bats. Rarely, animal coronaviruses can infect people and then spread between people such as with MERS-CoV, SARS-CoV, and now with this new virus . Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919\nPassage: Additionally, a significant number of viruses can cause influenza-like syndromes, such as rhinovirus, parainfluenza virus, adenovirus, coronavirus, respiratory syncytial virus, Coxsackie B virus, echovirus, and metapneumovirus . Some of the above-mentioned viruses like adenovirus and mutated coronavirus could cause problems that are comparable to influenza viruses .", "Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens\nPassage: Overall, birds in the LAIV-LAIV group showed consistently high mucosal antibody responses across all three ELISA tests . The LAIV-IIV group also showed a good level of antibody response that was somewhat biased toward IgG response despite the fact that the IgA response observed in this group was not significantly different from the LAIV vaccinated groups . The single vaccination regimens administered at 3 weeks of age showed a trend that was similar to the 1-day-old vaccination result: no differences in anti-NP or IgG antibodies and higher IgA responses in LAIV groups compared with IIV groups . Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: decade and it has been reported to protect young individuals better than IIV . Importantly, recent studies showed that LAIV can pre-sensitize the population and, subsequently, synergistically boost the efficacy of IIV . It should be noted that the use of LAIV in poultry requires strict safety standards due to concerns about the possibility that wild type strains may circulate in domestic poultry without apparent clinical symptoms, undergo genetic reassortment with the vaccine virus, and produce novel virulent strains . An ideal poultry LAIV should not be able to revert to wild type virus or undergo reassortment with field strains. Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens\nPassage: protective efficacy of LAIV in 1-day-old chickens. Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: One of the perceived risks of vaccinating commercial poultry against influenza is the possibility of the vaccine protecting birds from disease without preventing replication and spread of the virus. We have demonstrated that a single dose of LAIV is able to induce stronger innate and mucosal IgA responses and protect young immunologically immature chickens better than a single dose of conventional IIV. Most importantly, priming with LAIV led to a synergistic serum antibody induction by IIV and enhancement of antibody cross-reactivity, thereby increasing the chance of protection from distantly related strains. Our prime-boost vaccine strategy requires further improvements to address", "Title: Estimating the number of infections and the impact of non-\nPassage: Case-based Title: Estimating the number of infections and the impact of non-\nPassage: Case-based Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: staff to undertake personal measures to reduce infection, such as wearing masks at all instances Title: Estimating the number of infections and the impact of non-\nPassage: and in some examples have implemented these interventions all on a single day.", "Title: Estimating the number of infections and the impact of non-\nPassage: Austria 1.1% Title: Estimating the number of infections and the impact of non-\nPassage: Austria measures Implemented at lockdown.22 16/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: Table l: Posterior model estimates of percentage of total population infected as of 28th March 2020.", "Title: Zika virus-induced acute myelitis and motor deficits in adult interferon \u03b1\u03b2/\u03b3 receptor knockout mice\nPassage: The fact that relative CMAP amplitude after spinal cord stimulation did not statistically correlate with VPS score suggests that damage upstream of spinal motor neurons may contribute to the hindlimb deficits. For example, CMAP amplitude was not reduced in two infected mice with overt paralysis . Paralysis in these animals could be caused by motor cortex, cerebellum, or brainstem dysfunction, as extensive infection was observed in these areas of the brain. While upper motor neuron disease is associated with rigid, rather than flaccid paralysis, we occasionally saw symptoms that could be interpreted as rigidity, such as walking with high haunches Title: Potential impact of diabetes prevention on mortality and future burden of dementia and disability: a modelling study", "Passage: We defined disability as the inability to independently carry out one or more activities of daily living, which included getting in or out of bed, walking across a room, bathing or showering, using the toilet, dressing, cutting food and eating. This definition of disability captures individuals who have difficulty maintaining independence and require supportive care. Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: The most common causes of disability globally are adult-onset hearing loss and refractive errors. Mental disorders such as depression, alcohol use disorders and psychoses are also among the 20 leading causes of disability . The pattern differs between the highincome countries and the low-and middle-income countries. In the lower income countries, many more people are disabled due to preventable causes such as unintentional injuries and infertility arising from unsafe abortion and maternal sepsis. The data also demonstrate the lack of interventions for easily treated conditions such as hearing loss, refractive errors and cataracts in low-income countries. Disability due to mental Title: Potential impact of diabetes prevention on mortality and future burden of dementia and disability: a modelling study", "Passage: Dementia was defined on the basis of the coexistence of cognitive impairment and disability, or a report of a doctor diagnosis of dementia by the participant or caregiver. Cognitive impairment was defined as an impairment in two or more functional tests or a score higher than 3.6 on the Informant Questionnaire on Cognitive Decline .", "Title: Variation in RNA Virus Mutation Rates across Host Cells\nPassage: genetic andmetabolic alterations in addition to p53 inactivation. To check the potential effects of these changes, we performed fluctuation tests in CT26 cells from an undifferentiated grade IV colon adenocarcinoma of a BALB/c mouse , but we found no significant differences with primary MEFs . Of note, BHK-21 are also tumor-forming cells, and the mutation rate was similar to the rate observed in MEFs or CT26 cells . This homogeneity in the VSV mutation rate was not an obvious a priori, because metabolic and mitotic activity should alter the availability of NTPs and hence could impact RNA replication fidelity, although Title: Influence of gene modification in biological behaviors and responses of mouse lung telocytes to inflammation", "Passage: Propidium iodide staining was used for cell cycle analysis of primary TCs and TCs SV40 as described in manufacturer. In brief, cells were collected and fixed in 75% ethanol at 4 \u00b0C for overnight. After centrifuging and washing, staining buffer with 0.5 ml PI/RNase was added to each tube for 15 min at room temperature. Samples were examined with a fluorescence-activated cell sorting flow cytometer and DNA histograms were analyzed with Flowjo 7.6.1 software. Each test was repeated thrice. Title: Influence of gene modification in biological behaviors and responses of mouse lung telocytes to inflammation", "Passage: , where cell nuclei were stained with DAPI. Dynamic alterations of TCs SV40 at 2, 5, 10, 20, 30, 50, or 60 generations were recorded automatically each 30 min for 48 h and cell morphological phenomes were presented each 12 h, respectively, in Additional file 1: Figure S1 . Figure 3 demonstrated that immuno-positive staining of the vimentin labeled with particle diameter at 10 nm, CD34 at18 nm, platelet-derived growth factor receptor \u03b1 at 25 nm, or ckit at 40 nm in lung TCs SV40 under transmission electronic microscopy. Tomography of TCs was taken immediately after transfer with SV40 tomography, Title: Evaluation of Ultra-Microscopic Changes and Proliferation of Apoptotic Glioblastoma Multiforme Cells Induced by Velogenic Strain of Newcastle Disease Virus AF2240\nPassage: 12 x 75 Falcon tubes and the cell cycle was analyzed by flow cytometer . Each experiment was assayed three times .", "Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers\nPassage: The risk for pandemic 2009 virus infection increased with the number of children <18 years of age living in the participant's household, which has previously been reported as a risk factor . In Victoria, the median age of persons with reported pandemic 2009 virus infection was 15 years, with 67% of all notifi ed casepatients being 5-17 years of age . Miller et al. also found that children were predominantly infected . This fi nding, coupled with the diffi culties of maintaining good respiratory etiquette in young children, is a plausible explanation for the effect of child number on infection Title: Influenza virus-related critical illness: prevention, diagnosis, treatment\nPassage: hospitalized children with influenza than in adults. Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: Of all 971 positive children, 890 were 4 years old or younger. The positive rate in this age group was significantly higher than that in children more than 4 years old . Children under 6 months were the most susceptible to respiratory viral pathogens with a positive rate of 14\u00c18% . Title: Host susceptibility to severe influenza A virus infection\nPassage: Extremes of age are well-recognised risk factors for severe disease. Children under the age of 5 years, and particularly those under 2 years, have consistently been found to be at high risk for severe disease and serious complications following IAV infection . Functional immaturity of the immune system, together with a failure to recognise IAV-related antigens, may largely explain this effect.", "Title: Influence of H7N9 virus infection and associated treatment on human gut microbiota\nPassage: is worthy of note that Enterococcus and Enterobacter have been reported to play crucial roles of the gastrointestinal tract infections, lower respiratory tract infections, skin and soft-tissue infections, urinary tract infections, endocarditis, CNS infections, septic arthritis, intra-abdominal infections, and ophthalmic infections 21, 22 . Title: Secretome of Intestinal Bacilli: A Natural Guard against Pathologies", "Passage: major role in the development of GALT -gut lymphoid tissue associated with the gastrointestinal mucosa -and in the diversity of the primary antibody population in rabbits . Bacillus spp. like other strains isolated from human stool were able to bind the human norovirus strains, the cause of acute viral gastroenteritis and foodborne diseases, around the outer cell surfaces and pili structures . The interaction between virus and bacteria is hypothesized to help the host immune system to better recognize infectious particles. Title: Influence of H7N9 virus infection and associated treatment on human gut microbiota", "Passage: Remarkably, chronic complex diseases have been associated with gut microbiota. Although the intestinal microbiota is generally stable in healthy individuals over long periods of time, antibiotics can significantly reshape the gut microbiota, allowing exogenous microbes to outgrow commensal bacteria and cause permanent changes in varying states of disease 6, 11, 12 . Probiotic agents, which beneficially affect the host by improving the gut microbial balance, have been used for the prevention and treatment of respiratory tract diseases to avoid bacterial translocation 13, 14 . It is noteworthy that gastrointestinal distress symptoms were observed in some of our recently reported cases Title: Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants\u2014A community-based randomized intervention", "Passage: Changes are likely occurring also in the microbiota of the human gastrointestinal tract, which can itself be considered infectiousi.e., acquired from the environment. Gut microbial populations have been shown to impact a variety of metabolic processes including inflammation, angiogenesis, immunity, and insulin resistance . They may have an important role in growth, as relative proportions of bacterial phyla have been shown to be responsive to weight change . Thus, childhood infectious conditions, some of which dramatically impact the gut microbiota at least in the short term, may well have long-term effects on the microbiota and as such may well play", "Title: Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic\nPassage: Three hundred ninety-one patients with A were admitted from 26 September 2009 to 10 February 2010 in the 69 ICUs participating in the screening registry and were included in this study. Among them, 349 had a confirmed influenza A infection. This subset of 391 patients represents 36.7% of the whole cohort of French influenza-infected adult ICU patients ; they had the same overall characteristics, except for a higher rate of immunosuppression . Tables 2 and 3 show the baseline characteristics and main risk factors for flu recorded in these patients according to survival or to the intensity of ventilatory support. Title: Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study", "Passage: Of the 200 enrolled in this study, 25 patients were excluded from the analysis of the data. Of these, 21 patients had incomplete sampling and four patients met exclusion criteria. The characteristics on admission of the 175 patients included in our analysis study group are presented in Table 1 . Mean age was 62 years; roughly one-third had CAP, one-third had HAP, and one-third had VAP. The median hospital and ICU lengths of stay prior to enrolment were six days and nine days , respectively. Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: In the period of the study, 1789 patients were admitted to the ICU and 13 PGWH patients were included. There were 10 male patients and 3 female , with a mean age of 30 years . There were no self-inflicted lesions . Glasgow Coma Scale at admission was 8 or less in 10 patients. On admission, 7 patients were anisocoric, 8 presenting shock, 5 had associated body lesions from another gunshot wound . Mean SAPS 3 was 67 and mean Apache II, 26 . The CT scan findings were: midline shift in 8 patients, 7 single lobe haemorrhages , and Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: Results: A total of 116 patients were enrolled from April 2014 to September 2015. Fifty-two patients were assigned to IABP group and 64 patients to control group. The mean age was 64 \u00b1 8 years in the IABP group and 67 \u00b1 9 years in the control group . The median LVEF was 40 % in the IABP group and 40 % in the control group and the median EuroSCORE was 6 vs. 6 , P = 0.873, respectively. The primary outcome was observed in 40.4 % in the IABP group and 37.5 % in the control group after cardiovascular", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: All hospitalised cases had a benign clinical evolution except four, two reported in Italy and two reported in France, all of whom developed viral pneumonia. All three cases who were aged 65 years or over were admitted to intensive care and required respiratory support and one French case died. The case who died was hospitalised for 21 days and required intensive care and mechanical ventilation for 19 days. The duration of hospitalisation was reported for 16 cases with a median of 13 days . As at 21 February 2020, four cases were still hospitalised. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: 2 days to be hospitalised. Title: Quantifying social distancing arising from pandemic influenza", "Passage: The total population size of Sydney was NZ810 700, of which at least 14 130 were admitted to hospital and approximately 3500 died as a result of influenza infection . Based on a survey of 600 establishments covering 106 923 employees, the proportion of workers that were absent from duty as a result of influenza was 36.6% . This was considered as an unbiased estimate of the clinical attack rate, although we argue that the serological attack rate may have differed. Title: Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016\nPassage: Of the 1722 patients, 96 were admitted to a hospital for a reason other than acute respiratory infection and developed ILI symptoms \u226548 h after admission and were classified as nosocomial influenza. Of these 96 cases, 35 were aged 18-64 years, 22 were aged 64-74 years, 39 \u2265 75 years and 43 were female. Eighty patients presented \u22651 influenza risk factor and 36 had received the influenza vaccine .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: in humans . Currently, NA-specific antibody responses are not considered a correlate of protection . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx . LAIV immunization induces serum antibody responses, mucosal antibody responses , and T cell responses. While robust serum antibody and nasal wash antibody responses are associated with protection from infection, other immune responses, such as Title: Current and Novel Approaches in Influenza Management", "Passage: LAIV viruses in the nasopharynx elicit immune response that epitomizes a natural influenza infection. For this reason, LAIV has shown some superiority over the IIV in terms of the induction of mucosal immunity via secreted immunoglobulin A . Use of the LAIV has proven to be safe in children and immunocompromised persons . The most spelt-out advantage is the \"non-invasive\" capacity of the attenuated viruses and this had made it suitable to use for all categories of vaccines, although LAIVs are not recommended for people with underlying chronic medical conditions . A typical setback to the use of the LAIV Title: La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys", "Passage: the lymph nodes and major organs, with subsequent infection of the upper respiratory tract followed by infection of the brain and eventually the spinal cord. By day six, mice began to succumb to infection in the high dose group showing signs of paralysis whereas mice in the low dose group failed to show clinical signs at this time, but would have succumbed later in infection. These results indicate that LACV replicates to low to moderate levels in peripheral tissues in weanling mice, with the nasal turbinates rather than striated muscle being the major site of replication. Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: Overall, birds in the LAIV-LAIV group showed consistently high mucosal antibody responses across all three ELISA tests . The LAIV-IIV group also showed a good level of antibody response that was somewhat biased toward IgG response despite the fact that the IgA response observed in this group was not significantly different from the LAIV vaccinated groups . The single vaccination regimens administered at 3 weeks of age showed a trend that was similar to the 1-day-old vaccination result: no differences in anti-NP or IgG antibodies and higher IgA responses in LAIV groups compared with IIV groups .", "Title: Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review\nPassage: required for potential growth of pathogen population in the environment, exposure dynamics, incubation period, and delays in reporting. Title: Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review", "Passage: Infections are typically revealed after the incubation period, t inc , ; which is associated with patient's physiology, whose distribution depends on the type of infection ). After symptoms start, only a proportion of the infected individuals seeks medical assistance , and for only a proportion of these cases further diagnostic testing will be conducted and recorded in the public health system. This introduces a further time lag, t det , between the time when infected individual approaches the health system and the actual appropriate laboratory detection with diagnosis . Even in a simple scenario, the temporal lag between the Title: Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies", "Passage: The physician questionnaire contained three questions about environmental exposures that had been previously suggested to be possibly associated with the onset of JDM . These included whether the patient had any documented infections, received any immunizations or took any medications within 6 months before illness onset. The questionnaire also included an additional open-ended question about other environmental exposures within 6 months before illness onset relating to other possible triggers of disease and to specify these and when they occurred. Stressful life events were categorized as major vs minor and as One hundred and twenty-one patients were tested by IP immunoblotting. Title: Development of a Symptom Score for Clinical Studies to Identify Children With a Documented Viral Upper Respiratory Tract Infection", "Passage: Although it may seem surprising that a viral etiology was not identified in \u03fe40% of children with cold symptoms using the most sensitive molecular techniques currently available, the definition of a \"cold\" is actually somewhat nebulous . In one study of 215 adults who reported they were developing a cold, only 54% had at least one respiratory symptom and only 17% met Jackson criteria for a cold . Thus, the use of a \"clinical cold\" as the entry criterion for clinical trials on the efficacy of a potential viral URI treatment includes participants with heterogeneous clinical conditions and may bias", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Notwithstanding this progress, there remains a disproportionate burden of disease in low-and middle-income countries, where more than 90% of pneumonia cases and deaths occur. The incidence in high-income countries is estimated at 0.015 episodes per child year, compared to 0.22 episodes per child year in low-and middle-income countries . On average, 1 in 66 children in high-income countries is affected by pneumonia per year, compared to 1 in 5 children in low-and middle-income countries. Even within low-and middleincome countries there are regional inequities and challenges with access to health care services: up to 81% of severe pneumonia deaths occur outside Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: odds of severe pneumonia by 2.7 times in low-and middle-income countries and 1.3 times in highincome countries. Markers of undernutrition are strong risk factors for pneumonia in low-and middle-income countries only, with highly significant odds ratios for underweight for age , stunting and wasting . Household crowding has uniform risk, with odds ratios between 1.9 and 2.3 in both low-and middle-income countries and high-income countries. Indoor air pollution from use of solid or biomass fuels increases odds of pneumonia by 1.6 times; lack of measles vaccination by the end of the first year of age increases odds of pneumonia by Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: 1.8 times . It is estimated that the prevalence of these critical risk factors in low-and middle-income countries decreased by 25% between 2000 and 2010, contributing to reductions in pneumonia incidence and mortality in low-and middle-income countries, even in countries where conjugate vaccines have not been available . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: a hospital . In addition to a higher incidence of pneumonia, the case fatality rate is estimated to be almost 10-fold higher in low-and middle-income countries as compared to high-income countries .", "Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Suspected clustering cases are defined when one confirmed case and at the same time, one or more cases of fever or respiratory infection are found in a small area within 14 days. Title: Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1 virus infection: an observational cohort study", "Passage: According to the initial chest radiographs, 80 patients had pneumonia and were divided into two groups: the bronchopneumonia group and the segmental/lobar pneumonia group . In pneumonia patients, pneumonic infiltrations appeared within 48 h of fever onset in 68 patients . When we analyzed the inpatients according to age , the rates of pneumonia in each age group were 36.0% , 45.2% and 8.8% , respectively. The severe pneumonia was predominant in the older age groups , 48.9% and 50% , respectively). Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America\nPassage: pneumonia in a sub-group of susceptible young adults in April 2009. This cluster would have represented the apex of the infectious pyramid. Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Under the above circumstances, 2 or more confirmed cases are found, and there is the possibility of human-tohuman transmission due to close contact or infection due to co-exposure, then it is determined as a clustered case .", "Title: Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential\nPassage: For the full collection of clinical isolates that had whole genome short-read sequencing data , reads were aligned to the 3D7 reference genome using bowtie2 . Samples with less than 10 million reads mapping to the reference were excluded, as samples with less than this amount had reduced coverage across the genome. Bam files were processed according to GATK's Best Practices documentation . Joint SNP calling was done using Haplotype Caller . Because clinical samples may be polyclonal , diploid calls were initially allowed, followed by calling the major allele at positions with heterozygous calls. If the major allele was Title: Generation and comparative genomics of synthetic dengue viruses", "Passage: Three DENV cDNA samples were sequenced and analyzed: one of the samples was the wildtype strain, with the WT sequence used as a reference genome for NGS analysis. The two synthetic variants of the virus were synthesized using two different methods . The WT sequence can be found in Additional file 1, section 8. Sequencing libraries were prepared using the INCPM DNA-seq protocol, and sequenced 2 \u00d7 150 on an Illumina MiSeq nano v2 PE150. Sequenced reads were mapped to a reference genome using BWA MEM v0.75 . Among all read-pairs with the same alignment, a single representative read was Title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture\nPassage: assembled chromosomes. Title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture\nPassage: GRCh38p1.chrY , but absents from HuRef.chrY and YH.chrY that did not use BACs for sequencing and assembling, they are unlikely shared.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: DNA Vaccines\u2014How Far From Clinical Use?", "Passage: The delivery vector has to offer a sufficient capacity to efficiently package DNA/RNA per se, which is an obstacle especially for longer plasmid DNA , in order to enable delivery of a sufficient amount of molecules per target cell . The delivery system has to show stability against serum proteins that may form a protein corona around the NC and thereby affect its targeting and uptake efficiency . After uptake by the cell, the NC cargo has to evade endo/lysosomal degradation and to enter the cytoplasm by endosomal escape . While released mRNA is translated directly in the cytoplasm, Title: Recombinant vector vaccine evolution", "Passage: Evolution is not the only consideration in designing a recombinant vector vaccine, and the model helps us identify vaccine properties that promote efficacy. First the vaccine should elicit an immune response that rapidly clears the pathogen . Second, the vaccine should elicit a large response to this antigen. This requires that the antigen rapidly elicits immunity , and also requires a high vaccine viral load to generate a large response. Engineering this requires tackling a trade-off between avoiding vaccine clearance but allowing for rapid clearance of the pathogen . Vaccines designed to express the antigen in a form that is Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: comparison of the properties of several strains that are commonly used as DNA vaccine carriers is presented in Table 1 . , and inside the DCs, the antigen gene is expressed as protein, which will later be presented by class I or II MHC and delivered to CD4+ or CD8+ T cells.", "Title: The Failure of R (0)\nPassage: He demonstrated that all three statements can be false. The first, as we have noted, can fail due to the presence of backward bifurcations. The second can fail when control efforts are applied unevenly across different host types , since R 0 is determined by averaging over all host types and does not directly determine the control effort required to eliminate infection. Title: The Failure of R (0)\nPassage: already present but would not be strong enough to invade. Finally, the threshold value that is usually calculated is rarely the average number of secondary infections, diluting the usefulness of this concept even further. Title: The Failure of R (0)\nPassage: illustrates the wide variety of values that are presented as being \"the\" R 0 value for a specific disease. Title: The Failure of R (0)", "Passage: G\u00f3mez-Acevedo and Li investigated a mathematical model for human T-cell lymphotropic virus type I infection of CD4 + T cells that incorporates both horizontal transmission through cell-to-cell contact and vertical transmission through mitotic division of infected T cells. They assumed that a fraction \u03c3 of the infected cells survive the immune system attack after the error-prone viral replication. Under the biologically sound assumptions that the fraction \u03c3 should be very low and the rate of the mitotic division should be high, their model has a bifurcation that predicts persistent infection for an extended range of the basic reproduction R 0", "Title: Host resilience to emerging coronaviruses\nPassage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea. Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: The clinical presentation of MERS varies from asymptomatic to severe pneumonia with acute respiratory distress syndrome , septic shock, and multiple organ failure, often resulting in death. Most patients with MERS develop severe acute respiratory illness accompanied by fever, cough, and shortness of breath . Progression to pneumonia is swift-usually within the first week -and at least one-third of patients also present with gastrointestinal symptoms . MERS progresses much more rapidly to respiratory failure and has a higher case fatality rate than SARS . Unlike SARS, however, infection with MERS-CoV is generally mild in healthy individuals but more severe in", "Title: Estimating the incidence and diagnosed proportion of HIV infections in Japan: a statistical modeling study\nPassage: incubation period of 12.3 years. The estimate by Munoz & Xu was obtained from the Multicenter AIDS Cohort Study with \u03b7 = 10.0 and k =1.3, and the median incubation period is 7.5 years. All three estimates have been used in the present study to address uncertainty with respect to the incubation period. In addition to Eqs. and , we have also explored the over-dispersed likelihood function, employing the negative binomial distribution with time-independent dispersion parameter for HIV and AIDS counts, respectively, and compared the Akaike Information Criterion against Poisson distributed likelihood, as part of sensitivity analysis. Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: that an incubation period within that range would be consistent with the predictions of most investigators , and the modal statement of central tendency. Title: Quantifying social distancing arising from pandemic influenza\nPassage: We do not observe i and must infer it from the daily death and/or hospitalization data. In the case of deaths ), we must account for the time delay between infection and death. The time from symptom onset to death was remarkably similar across all age groups with a mode of 7 days . We add 1.5 days for the incubation period and round to the nearest integer, so that tZ9. Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Sartwell and others have shown that the natural logarithm of incubation periods of acute infectious diseases tend to follow a normal distribution; hence the incubation period follows a log-normal distribution specified by the median incubation period and a dispersion factor . In a normal distribution, approximately twothirds of the data fall within one standard deviation of the mean; similarly in a log-normal distribution, approximately two-thirds of cases develop symptoms between median/dispersion and median \u00d7 dispersion. For each pathogen all observations were pooled together to form a single set of doubly interval censored observations; each data point contained a range of", "Title: Consequences of delays and imperfect implementation of isolation in epidemic control\nPassage: Isolation of infected hosts disconnects the infection pathway for diseases that are transmitted human-to-human and should, in principle, be 100% effective, yet it has not always stopped incipient outbreaks from burgeoning into full-blown epidemics. In this paper we called attention to the fact that a major reason may be \"too little, too late\", meaning the identification of infected hosts may not be sufficiently thorough and are too often subject to delays. We sought a mathematical model that could offer guidance on the response needed to contain an outbreak, as well as predict the consequences when one falls short. Our aim Title: Consequences of delays and imperfect implementation of isolation in epidemic control", "Passage: Of major concern is what happens if the response capability is inadequate, that is, if the isolation probability falls below the required minimum, or if the required identification time is not met. Our next result addresses this scenario. Title: Consequences of delays and imperfect implementation of isolation in epidemic control\nPassage: The main concern of this paper is the effect of isolation on disease outcome starting from a small outbreak. To this end, the following conserved quantities will be of major help: Title: Consequences of delays and imperfect implementation of isolation in epidemic control", "Passage: time, how quickly local authorities must act to prevent a full-blown outbreak. Our model predicts the nature of the endemic state that follows should the response be inadequate, and the extent to which a stronger response can ameliorate the severity of an outbreak. It offers crucial information to health authorities such as estimates on the fraction of the population that can be expected to fall ill, and answers theoretical questions such as the potential benefits of longer durations of isolation.", "Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Secondly, the R0, the basic reproduction number, is correctly described as the average number of infections each case causes. But it lacks two key ideas: 1) the 0 after the R implies the native state, which is a fully susceptible population and without any control measures. R is the effectiive number and can include the impact of control measures. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: Researches showed that the R 0 of severe acute respiratory syndrome was about 2.7-3.4 or 2-4 in Hong Kong, China . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 . The transmissibility of the Middle East respiratory syndrome is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 , with the inter-human transmissibility of the disease was about Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: totally susceptible population . When R 0 is greater than one, there is a likelihood that the infection will to continue to spread; however if R 0 is less than one, then the infection will eventually die out. For this reason, estimating the basic reproduction number is paramount for assessing the effectiveness of different intervention strategies. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: . It seems that the majority of human cases of MERS-CoV, even when numbers appear to increase suddenly, do not readily transmit to more than one other human so to date, the localized epidemic of MERS-CoV has not been self-sustaining . That is to say, the basic reproduction number -the average number of infections caused by one infected individual in a fully susceptible populationhas been close to one throughout various clusters and outbreaks. If R 0 was greater than 1, a sustained increase in case numbers would be expected. Some R o calculations may be affected by incomplete case contact", "Title: Viable Influenza A Virus in Airborne Particles from Human Coughs\nPassage: each cough, the cough-generated aerosol was collected using the aerosol sampler. This procedure was repeated for a total of six coughs from each subject. Title: Viable Influenza A Virus in Airborne Particles from Human Coughs", "Passage: Cough-generated aerosols were collected using a cough aerosol particle collection system similar to that described previously. An ultrasonic spirometer measured the volume and flow rate of each cough, and a modified 10 liter piston-style mechanical spirometer served as an accumulation chamber for the cough aerosol. A stainless steel tray was attached to the piston of the mechanical spirometer to collect any large ballistic cough spray droplets that impacted the piston. Cough aerosol particles were collected using an SKC BioSampler with a 5 ml vessel containing 5 ml of viral transport media consisting of Hank's Balanced Salt Solution supplemented with 0.1% Title: Viable Influenza A Virus in Airborne Particles from Human Coughs", "Passage: Finally, some important limitations of this study must be acknowledged. First, because of the small sample size, these results need to be interpreted with caution. More studies with larger numbers of patients and with a broader range of medical conditions will be needed to fully understand the amount of viable airborne virus that is projected into the environment by patients. Second, our experiments focused on viable virus released during coughing. However, this does not mean that infectious virus is not released during other respiratory maneuvers such as breathing and speaking. Third, we asked the study participants to inhale deeply and Title: Viable Influenza A Virus in Airborne Particles from Human Coughs", "Passage: aerosol particles are able to deposit deeper in the respiratory tract than droplets administered by intranasal inoculation. The amount of influenza A virus detected in cough aerosols in this study was probably much lower than would be seen in a severe influenza pandemic. First, studies of nasopharyngeal swabs from patients with naturally occurring influenza infections have shown that influenza viral shedding typically peaks on or around the first day of acute respiratory illness. Patients in our study typically presented at the clinic the day after their symptoms developed, which was after the expected peak in nasopharyngeal viral shedding. The amount", "Title: Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease\nPassage: UBF binding also promotes stabilization of SL-1 interaction with the rDNA promoter . The resultant UBF/ SL-1 complex then facilitates recruitment of an initiationcompetent subpopulation of Pol I, defined by the presence of the basal regulatory factor RRN3 , to form a productive PIC at the rDNA promoters . Furthermore, UBF interacts with the entire transcribed region , not just promoter elements, and can regulate promoter escape and Pol I elongation in response to growth stimuli . Title: Circular RNAs: a rising star in respiratory diseases\nPassage: In addition, circRNAs bind to RBPs in a spongeadsorbed form and are capable of storing, sorting and transferring RBPs, thereby inhibiting their function and regulating the post-transcriptional process . Title: Identification of MicroRNA-Like RNAs in Mycelial and Yeast Phases of the Thermal Dimorphic Fungus Penicillium marneffei", "Passage: protein. RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules involved in mitosis, while cytochrome P450 catalyses diverse reactions in fungal primary and secondary metabolism, and xenobiotic detoxification. As for PM-milR-M2, 20 potential targets were predicted, which include 13 transposon or transposable elements and seven conserved hypothetical proteins. Title: Human core duplicon gene families: game changers or game players?", "Passage: The RANBP2 protein encoded by the progenitor gene is primarily localized within the periphery of the nuclear envelope and is thought to be required for cargo import and export . Hence, the RGPD gene family members may be modifiers of this function. Interestingly, RANBP2 was also shown to be involved in resistance against Simian Immunodeficiency Virus . It is thus possible that the expansion of RGPD genes is the result of an arms race between virus evolution and host resistance acquisition. The Ranbp2 knockout in mice is homozygous lethal.", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: mental health ranked seventh for visitors with 1, 502 searches submitted, and ninth for registered users with 1, 459 interested in the topic. The remaining three topic areas with many available reviews were preferred by either visitors or registered users . Addiction/substance use ranked third for visitors with 2, 283 search page views in 2010. Adult health and adolescent health ranked sixth and eighth respectively for registered users with 1, 778 and 1, 636 registered users indicating interest in each of these topics. Title: Global trends in research related to social media in psychology: mapping and bibliometric analysis", "Passage: Step 1: The topic search query phrase \"\" was applied to gather all the publications with those phrases in their titles, abstracts, or keywords. The documents published during the period from 2004 to 2015 were included in the study while the years 2016 and 2017 were excluded, as those years are still open for new issues. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis", "Passage: We conducted an exploratory analyses of topical data using a set of unique keywords and their frequencies to examine the topic coverage, major topics and their interrelations in RCT articles. The main goal in topical analyses is to understand the topical distribution of a dataset, i.e. what topics are covered and how much of each topic is covered in a scientific discipline . The Table 1 Included high-impact-factor medical journals General medicine journals . Based on the most frequently used keywords , a word cloud was created from text that the user provides and more emphasis was placed on words Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: The top 10 topic areas of interest of registered users and the top 10 topic areas of interest of visitors of http:// www.health-evidence.ca, as well as the availability of review evidence by methodological quality, are identified in Table 1 . The top areas of interest and the total number of reviews available included: addiction/substance use , adolescent health , adult health , child health , chronic diseases , communicable disease/infection , healthy communities , injury prevention/safety , mental health , nutrition , parenting , physical activity , reproductive health , and social determinants of health .", "Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan\nPassage: PEDV is believed to infect pigs by both direct and indirect fecal-oral routes. Due to the scales and complexities of modern swine production systems, PEDV is likely transmitted between farms via diarrheic feces or vomitus; contaminated environmental sources involving clinically or sub-clinically infected pigs; trailers used to transport livestock, manure, or food sources; farmers or visitors wearing contaminated clothes; or wild animals and birds . Other potential sources include contaminated fomites , food ingredients or additives, and environmental features such as wind direction, farm altitude, terrain slope, and tree coverage . After an initial outbreak, PEDV may spread at an Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan", "Passage: Although researchers believe that PEDV infections primarily result via fecal-oral routes, the rapid regional spread of the disease raises the possibility of airborne transmission . Support for this hypothesis includes an identified correlation between disease-spread direction and prevailing wind direction , with environmental features such as land coverage, altitude, and slope possibly influencing airborne disease dissemination . To determine specific temporal and geographic relationships associated with PEDV strain transmission, we used phylogenetic, phylodynamic and phylogeographic methods to systematically evaluate potential temporal and spatial transmission routes among Taiwanese swine farms during the 2014 outbreak. Title: Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses", "Passage: to severe diarrhea, shed high quantities of PEDV in feces ranging from 3.96 x 10 10 to 7.57 x 10 10 (RNA copies/ml, , and had histopathological lesions of moderate to marked atrophic enteritis compatible with PEDV infection. The negative control pig showed no clinical signs, tested negative by PCR and had normal intestinal histomorphology. Title: Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses\nPassage: At day 21 of the study, all pigs were intra-gastrically inoculated with a suspension of 20 ml of PEDV-material obtained from mucosal scrapings from PEDV infected pigs following published procedures . The inoculation material was confirmed positive by PEDV RT-PCR and diluted to a cycle threshold value of 15 to 16. The inoculation material was prepared and kept refrigerated for 24h at 4\u00b0C prior to inoculation. The total duration of the study was 24 days.", "Title: Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis\nPassage: immunosuppression, specific comorbidities-chronic lung disease, heart disease, blood disorders-elderly and living in long-term care facilities are associated with a higher risk of severe viral pneumonia . Nevertheless, recent studies suggest that hMPV infection is an underappreciated cause of critical illness, also in previously healthy patients . Title: Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis", "Passage: Three different genotypes of hMPV were associated with severe CAP requiring ICU admission, which supports that all of them are able to cause severe infections in adult patients. The low number of cases of the three different hMPV lineages, the presence of coinfections and the retrospective nature of the study made impossible to analyze the clinical pattern and the evolution of the patients based on the genotype of the infecting hMPV. However, to date, there are no significant differences in the evolution or clinical manifestation between different genotypes of HMPV in adults in the outpatient setting . Title: Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt", "Passage: The most clinical signs significantly associated with the presence of HMPV were acute bronchitis , bronchial asthma with infection exacerbation , and bronchiolitis . Acute bronchitis was the most common diagnosis in adults , whereas bronchiolitis was most frequently diagnosed in children . Further, there was one two-year old patient International Journal of Microbiology 5 coinfected with AdV. Patients EG/476 and EG/478 suffered from the underlying diseases bilateral hydronephrosis and hypertension, respectively. To describe the circulation of HMPV in the Egyptian population, patients were grouped by age: 0-4 years, 5-14 years, 15-34 years, 35-60 years, and >60 years . HMPV Title: Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis", "Passage: half of the year and 16 in March-April. HMPV circulated every year later than influenza virus, being the epidemic peak of both infections separated by a period of 1-2 months. In fact, the 75% of cases of hMPV infections in patients admitted to ICU occurred out of the influenza epidemic period .", "Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris\nPassage: secretion to display for full length IgGs, they suffer drawbacks of their own, including the need for modifying the protein sequence to allow surface binding in particular cases. Moreover, re-capture following secretion introduces the risk of \"crosstalk\" between clones that could lead to the loss of the required genotype-to-phenotype relationship that is critical for efficient lead-cell isolation. Without a strong genotype-to-phenotype relationship built into the display system the issue of \"cross talk\" among clones in the same culture must be addressed through tedious experimental modifications . Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: We have presented the development of a novel dual-mode display and secretion technology in Glyco-engineered Pichia pastoris, and demonstrated the utility of this method in selecting mAb leads with variable affinities and high productivity. The combination of display and secretion in the same clone enables the continuity and fidelity of the antibody discovery process and could lead to shortened maturation cycle and desirable lead developability. Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: Surface display boasts the ability to link genotype to phenotype. In the classical antibody display paradigms, sorted clones are isolated and their genotypes are subcloned into new production hosts. This cloning step involves screening multiple clones to isolate ones with defined properties. The anchored Fc system side-steps the need for these additional steps by combining selection of antibody affinity and production host in a single experiment. Libraries can be generated and displayed in the cell line of choice, such as Glyco-engineered Pichia pastoris. Selected clones can be fermented directly in small or large scale vessels to generate material for in Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: The use of surface display for discovery of novel monoclonal antibodies has evolved dramatically over the last decade. Multiple antibody display formats have been proposed and implemented in both prokaryotic and eukaryotic systems . Despite these advances, the majority of these efforts have focused on the utilization of antibody fragments as surrogates for mAb lead identification and maturation rather than full-length immunoglobulin G proteins . While the antigen binding domains of antibodies can be used to evolve binding affinity, they poorly predict the physicochemical characteristics and expressibility within the context of the fulllength cognate IgGs. In addition, these approaches necessitate", "Title: Proteomics Analysis of the Nucleolus in Adenovirus-infected Cells\nPassage: Many other plant and mammalian viruses have also been shown to interact with the host cell nucleolus from human immunodeficiency virus to Kaposi sarcoma herpesvirus . We therefore wanted to use a systematic and unbiased approach to examine the fate of the nucleolus during a viral infection using an established model system. Title: Nucleolus: the fascinating nuclear body", "Passage: Within the last few years, increasing evidence has revealed that viruses require the nucleus and in particular the nucleolus to target proteins indispensable for their replication. An increasing number of key proteins from both DNA-and RNA-containing viruses are localized in the nucleolus: viruses of the family Herpesviridae, Adenoviridae, Hepadnaviridae, Retroviridae, Rhabdoviridae, Orthomyxoviridae, Potyviridae, Coronaviridae and Flaviviridae, encode such proteins. Viruses have developed diVerent strategies to facilitate targeting of their proteins to the nucleolus: it was reported that the sequences of certain viral proteins harbor NoLS and NES . Recently it was demonstrated by mutagenesis that the nucleocapsid protein of infectious Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: Of importance, the nucleolus is also the target of viruses including HIV-1, hCMV, HSV and KSHV, as part of their replication strategy . Proteomics studies analysing the nucleoli of cells infected with Human respiratory syncytial virus , influenza A virus, avian coronavirus infectious bronchitis virus or adenovirus highlighted how viruses can distinctively disrupt the distribution of nucleolar proteins . Interestingly, both HIV-1 regulatory proteins Tat and Rev localise to the nucleoplasm and nucleolus. Both their sequences encompass a nucleolar localisation signal overlapping with their nuclear localisation signal , which governs their nucleolar localisation . Furthermore, Tat and Rev interact with Title: Proteomics Analysis of the Nucleolus in Adenovirus-infected Cells", "Passage: nucleus are inhibited, and a number of viral nucleolar antigens accumulate in the nucleoli of infected cells . Moreover, two cellular nucleolar antigens, UBF 1 and B23.1, have been shown to be sequestered into viral DNA replication centers where they affect viral DNA replication . Thus, there is clear evidence that adenovirus infection has a substantial impact on the composition and function of the nucleolus. What is not clear is whether the sequestration of cellular nucleolar antigens is limited to a small number of proteins or widespread. In addition, it is unclear whether adenovirus primarily modulates the nucleolus for replicative", "Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France\nPassage: Among H1N1v negative single infections, the most prevalent viruses were rhinovirus , followed by parainfluenza viruses 1 to 4 , adenovirus , human coronavirus 229E, OC43 and NL63 and respiratory syncytial virus A and B . In addition, RespiFinder19H assay identified three patients with bacterial infection, two with Mycoplasma pneumoniae and one with Bordetella pertussis . No single infection by influenza B, hMPV, Chlamydophila pneumoniae or Legionella pneumophila was identified . Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France", "Passage: assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19\u00ae. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus , followed by parainfluenza viruses and adenovirus . 70.6% of H1N1v cases were identified in patients Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France", "Passage: Influenza infections were mainly detected in patient under 40 years old and no case was found in patients older than 65. These results corroborate previous data suggesting that past seasonal H1N1 infections or vaccination may give partial crossed protection . We have previously shown that the neutralizing titers against pandemic H1N1v virus correlate significantly with neutralizing titers against a seasonal H1N1 virus, and that the H1N1v pandemic influenza virus neutralizing titer was significantly higher in subjects who had recently been inoculated by a seasonal trivalent influenza vaccine . Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France\nPassage: Overall, 68 patients were then positive for H1N1v, one for H3N2 and 212 for non influenza pathogens. There were 245 single infections and 36 mixed infections .", "Title: Use of daily Internet search query data improves real-time projections of influenza epidemics\nPassage: The CDC defines ILI as a 'fever or greater) and a cough and/or a sore throat without a KNOWN cause other than influenza' and per cent ILI is the percentage of the total patient visits related to an ILI. Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection\nPassage: clinical case definition of ILI therefore became \"an acute respiratory illness with a measured temperature of \u2265 38 \u00b0C and cough, with onset within the past 10 days\". Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection", "Passage: The proposed changes to the ILI case definition should result in enhanced specificity without greatly compromising the definition's sensitivity . These changes allow for a better alignment of the case definition of ILI with that of SARI. They also clarify some aspects of the previous ILI case definition that could be misinterpreted by health-care providers, including those working in sentinel sites and national influenza centres and influenza epidemiological unit surveillance officers. 20 which, in turn, was based on criteria set, as part of the integrated management of childhood illness strategy, for pneumonia and severe pneumonia . For children younger than Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: ILI was defined as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. Every week, all GPs of the sentinel network were encouraged to collect a nasal swab from the first two patients who presented ILI since less than three days. After being tested for influenza viruses, the 994 swabs collected in 2011 and 2012 are frozen at -80\u00b0C at the university hospital center laboratory.", "Title: Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms\nPassage: with correlation coefficient R = 0.998 Room characteristics are shown in Fig 3. As it can be seen, the test room used in the test has typical characteristics describing leakage. Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis", "Passage: Under normal conditions, the endothelium plays the role of a selective permeable barrier to regulate plasma fluid exchange, as well as molecules and cells trafficking. Disruption of cell junctions, with combination of cell retraction process, lead to the loss of the vascular endothelium barrier function. In such conditions, fluids and proteins infusion are ineffective because of the immediate leakage to the interstitial space with a worsening of the respiratory failure without any efficacy on the hemodynamic state. This mechanism is similar to that reported by Clarkson in 1960 and is explained by a plasma leakage which was also described in Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis", "Passage: In our patient, hemodynamic investigations using echocardiography and the PICCO system showed hypovolemia with low filling pressures and without any ventricular dysfunction. An elevated amount of extravascular lung water as well as an increased vascular permeability were also observed. This result is confirmed by the chest CT scan findings, showing a large amount of water in the alveoli, in the perivascular and in the pleural space. The pleural effusion was exudative and contained a high quantity of protein which can be explained by a protein leakage rather than by an inflammatory origin. Title: Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis\nPassage: the vessel to the interstitial space.", "Title: Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt\nPassage: Human metapneumovirus is an enveloped, singlestranded negative-sense RNA virus that has been classified in the Metapneumovirus genus of the Paramyxovirus family and it is most closely related to respiratory syncytial virus . The genetic profile of the virus consists of 13,350 nucleotides, comprising the nucleoprotein , phosphoprotein , matrix protein , fusion protein , matrix proteins , small hydrophobic protein , glycoprotein , and RNA-dependent RNA polymerase . The fusion and attachment proteins are the major HMPV surface glycoproteins. The HMPV F gene codes for a class 1 viral fusion protein that mediates virus entry through both attachment and fusion Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: Human metapneumovirus is a single-stranded RNA virus in the family Paramyxoviridae and closely related to human respiratory syncytial virus . HMPV causes respiratory disease similar to RSV, ranging from mild upper respiratory infection to bronchiolitis and pneumonia . HMPV infections are seasonal and coinfection with other respiratory pathogens is common . The HMPV genome is approximately 13 kb and comprises eight open reading frames encoding nucleoprotein , phosphoprotein , matrix protein , fusion glycoprotein , transcription enhancer protein , small hydrophobic protein , attachment glycoprotein , and large polymerase protein . The membrane glycoproteins F and G sequences are used Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: Text: Human metapneumovirus is a single-stranded RNA virus in the family Paramyxoviridae and closely related to human respiratory syncytial virus . HMPV causes respiratory disease similar to RSV, ranging from mild upper respiratory infection to bronchiolitis and pneumonia . HMPV infections are seasonal and coinfection with other respiratory pathogens is common . The HMPV genome is approximately 13 kb and comprises eight open reading frames encoding nucleoprotein , phosphoprotein , matrix protein , fusion glycoprotein , transcription enhancer protein , small hydrophobic protein , attachment glycoprotein , and large polymerase protein . The membrane glycoproteins F and G sequences are Title: Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt", "Passage: A multiple sequence alignment was compiled from a part of the FI subunit of the F gene using ClustalW in the MEGA version 4.0 software program . In MEGA, the Neighbor-Joining tree was calculated with the HKY85 model and a reliability of 1,000 replicates. The phylogenetic tree was rooted to Avian metapneumovirus C . The following sequences of the described HMPV subgroups and lineages were included in the phylogenetic analysis: DQ009484 .", "Title: Th17 profile in COPD exacerbations\nPassage: Th17 profile in COPD exacerbations of the mucus produced by goblet cells and less elimination of pathogens), metaplasia of squamous epithelial cells, hyperplasia of goblet-producing goblet cells and basal cells ), in addition to the loss of tight junctions that, under normal conditions, work as an impermeable barrier and protect the respiratory tract from pathogens, xenobiotics and other harmful particles. 9, 13 Once the damage is generated in airway epithelial cells, they secrete chemical mediators in order to generate and maintain an inflammatory response against foreign agents. 5 Cell death produced releases damage-associated molecular patterns such as heat shock proteins, Title: The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human", "Passage: stimulation of abnormal mucin gene expression and glycosylation pathways; and inappropriate triggering of other signaling pathways. Therefore, the mucins may contribute to disease pathology through deletion or expression of abnormal MUC genes, changes in the proportion of mucin genes expressed or the production of mucins with abnormal glycosylation. Title: Greater Microbial Translocation and Vulnerability to Metabolic Disease in Healthy Aged Female Monkeys\nPassage: The presence of abundant protective mucus and the resultant selection pressure to reduce bacterial diversity are both features that prevent metabolic disease development in animal experiments 12, 45 . The observed relationship between goblet cells, which produce mucus, and bacterial gene counts at the mucosa support this concept. Title: The immunoregulatory and allergy-associated cytokines in the aetiology of the otitis media with effusion.", "Passage: Goblet cells produce and secrete mucins, which are important glycoproteins in the mucociliary transport system of the middle ear and are the main component of middle ear effusions, responsible for the viscous properties of effusions. 51, 52 However, under disease conditions, alterations that occur in the middle ear and eustachian tube mucin metabolism, 53 in the structure of mucin glycoproteins 54, 55 and in the glycoconjugate expression in cilia and goblet cells 56 promote the dysfunction of the normal mucociliary transport system and the formation of effusion in the middle ear cleft.", "Title: Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool\nPassage: Immune responses to infectious agents have different out-comes that can either protect or fail to control disease. Protection from re-infection relies on the establishment of efficient secondary immune responses that require the generation of antigen-specific \"memory\" B and T lymphocytes. The generation and selection of T-cell dependent \"memory\" B cells involves distinct molecular mechanisms: immunoglobulin isotype recombination and somatic hyper mutation, both dependent on the expression of AID . Therefore, a long-standing paradigm defined memory B cells as IgM -IgG + isotype switched cells . Different lines of evidence indicate that this is not always the case. In humans, it Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires", "Passage: B cell receptor diversity within the na\u00efve B cell compartment results from the recombination of the variable , diversity , and joining genes in the heavy chain and VJ genes in the light chain during B cell maturation. During an infection, na\u00efve B cells are exposed to antigen in the secondary lymphoid organs and undergo activation and differentiation including somatic hypermutation and immunoglobulin class switching to produce high affinity Abs. Ag-activated B cells may undergo differentiation into Bmem or short and long-lived PCs. The differentiation into Bmem may occur with or without T cell help and in a germinal center Title: Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool", "Passage: Text: Immune responses to infectious agents have different out-comes that can either protect or fail to control disease. Protection from re-infection relies on the establishment of efficient secondary immune responses that require the generation of antigen-specific \"memory\" B and T lymphocytes. The generation and selection of T-cell dependent \"memory\" B cells involves distinct molecular mechanisms: immunoglobulin isotype recombination and somatic hyper mutation, both dependent on the expression of AID . Therefore, a long-standing paradigm defined memory B cells as IgM -IgG + isotype switched cells . Different lines of evidence indicate that this is not always the case. In humans, Title: A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve", "Passage: \u2022 The authors find that mAb 3I14 \"has 15 variable heavy chain and 7 variable light chain somatic mutations...\". How do the authors explain lack of extensive somatic hypermutation? Broadly neutralizing antibodies that target conserved epitopes on the hemagglutinin protein of influenza A viruses tend to have extensive somatic hypermutation on the heavy chain (CR9114, CR6261, CR8020, S6-B01, 2D04, etc. Is this due to the light chain assisting in antigen binding? This issue should be addressed.", "Title: Can informal social distancing interventions minimize demand for antiviral treatment during a severe pandemic?\nPassage: We examined a range of basic reproductive numbers 45] . All natural history parameters and ranges examined in the model are outlined in Table 1 and the parameters have been examined in all possible combinations. Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: can reduce the effective reproductive number below 1, because this will guide the response strategies in other locations. During the 1918/19 influenza pandemic, cities in the United States, which implemented the most aggressive and sustained community measures were the most successful ones in mitigating the impact of that pandemic . Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America", "Passage: The basic reproduction number , indicates the average number of people each infected person infects in a totally susceptible population. By contrast, the time dependent effective reproduction number , indicates the average number of people each infected person infects, given the current interventions in place, and any prior immunity that reduces the susceptible pool. The effective reproduction number is always less than or equal to the basic reproduction number and typically declines gradually as a disease spreads through the population and collective immunity increases. The effective reproduction number was calculated using an adaptation of the method of Bettencourt and co-workers Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Abstract: Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2.2, assuming a mean serial interval of 7.5 days . The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1", "Title: Globalization and emerging governance modalities\nPassage: Proposition Six: Good public health is directly linked to positive social, economic, and political development Uneven or ineffective development results in poverty and weak regime states. The 'social determinants of health' school holds, importantly, that good developmental policies contribute more overall to the health of the public than medically oriented individual intervention, no matter how sophisticated and successful the latter. Good development policies lead to improved population health; uneven and unsuccessful development leads to inequality, poverty, and deficient provision of clean water, effective sanitation, adequate shelter and diet, as well as the political problems that follow from these conditions 3 Title: Globalization and emerging governance modalities", "Passage: Proposition Two: Effective public health is dependent on sufficient social investment Overall, public health is losing comparative budget parity with the rising costs of curative medicine in the developed nations. In the United States, with overall medical costs once gain breaking out into double digit annual increases, the relative share of national budgets devoted to public health declines. Especially in times of economic downturn, and the absence of compelling crisis conditions, social investment in public health is uncertain in most national budgets. Title: Globalization and emerging governance modalities", "Passage: Health is a relative value. Achieving it is an uncertain objective. Potentially the demand for health-especially as defined by medical interventions-may be infinite in a social climate in which individuals seek and receive new interventions to extend life or improve some aspect of bodily well being . These observations clash with the languages and perspectives of the policy process in which notions of attacking problems, defeating social ills, or achieving victory in another war on something are commonplace. These rhetorical tropes serve well-recognized strategic and tactical means within the policy processes for mobilizing support, achieving agenda positions, and gaining budgetary Title: Globalization and emerging governance modalities", "Passage: Two oft-conflicting notions of authority contend within the contemporary public health paradigm. Optimizing the public's health in a world of expanding threats requires increased amounts of state intervention. However, in part because of the prospect of this increasing state intervention, and to side-step the challenge to the power of private interests associated with the creation of dangers to the public's health, some would shift the ground for responsibility for health to individuals, who would be required to take on new responsibilities to calibrate their social behaviors to promote their own health.", "Title: Factors influencing psychological distress during a disease epidemic: Data from Australia's first outbreak of equine influenza\nPassage: In the most recent data from the NSW Adult Population Health Survey the combined proportion of the population reporting 'high' or above psychological distress is 12.1% . In addition, recent data collected in rural communities suggests that these figures may be slightly higher in rural-dwellers with 'very high' psychological distress of 5% reported in one study and 13.4-13.8% for combined 'high'/'very high' psychological distress in another . These findings are of relevance in the current study as it would be expected that horse-ownership would be linked to rural and peri-urban residency. Title: Factors influencing psychological distress during a disease epidemic: Data from Australia's first outbreak of equine influenza", "Passage: The prevalence of the four levels of psychological distress for the whole sample during the equine influenza outbreak; were 39% of respondents reporting 'low', 27% reporting 'moderate' 20% reporting 'high' and 14% reporting 'very high' levels of psychological distress. Table 3 shows the proportion of respondents reporting each level of psychological distress for the main socio-demographic survey variables. Title: Factors influencing psychological distress during a disease epidemic: Data from Australia's first outbreak of equine influenza\nPassage: Details of the study sample are presented in Table 2 . In total, 2,760 respondents completed the online survey, and of these 15% were male and 84% were female. More than a half of the sample had no children. A total of 40.2% of the respondents had a tertiary level educational qualification. Title: Factors influencing psychological distress during a disease epidemic: Data from Australia's first outbreak of equine influenza", "Passage: The greatest prevalence of 'very high' psychological distress was reported for those respondents in the 16-24 age group , and the lowest prevalence was reported by those in the 55-64 age group and those under 16 . With regard to the remaining socio-demographic variables the highest prevalence of 'very high' psychological distress were recorded for those respondents who were female, those with one child, and those with no formal educational qualifications.", "Title: Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method\nPassage: Owing to its deep active site cleft, the NA has been an attractive target for drug design. Both zanamivir and oseltamivir were designed by modifying the sialic acid structure. The two FDA-approved clinical drugs were once successfully used to inhibit the spread of influenza viral progeny by binding to viral surface glycoprotein of neuraminidase . However, it has also been found from several clinical cases that oseltamivir failed to treat avian influenza virus. It is both antigenic drift and antigenic shift of segmented RNA genome of influenza viruses that have caused the NA inhibitor being resistant . Title: Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein", "Passage: NA inhibitors such as oseltamivir and zanamivir , and matrix protein 2 ion channel inhibitors such as amantadine and rimantadine . However, resistance development is a serious problem for antiviral drugs, particularly when the target viral proteins continuously undergo a high frequency of antigenic drift . Most human influenza viruses, including pandemic 2009 H1N1 and H7N9, are currently resistant to amantadine/rimantadine or oseltamivir . Therefore, identification of novel antiviral targets and development of antiviral drugs for the treatment of influenza virus infections are imperative. Title: In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1", "Passage: Most of the three best ligands have the O-glycoside and the apioside group as the functional group of modified oseltamivir . These ligands were AD3BF2D, CA1G3B and F1G4B. The apioside group greatly enhanced inhibitory activity 28 because it is similar to O-glicoside compounds that have inhibitory activity against neuraminidase, and especially hydrolize influenza virus sialidase . Title: Clinical review: Update of avian influenza A infections in humans\nPassage: daily for 4 days as post-exposure prophylaxis . The NA glycoprotein had a histidine to tyrosine substitution at position 274, conveying a markedly higher IC50 for oseltamivir . In one study, the viral count of HPAI H5N1 in nasal secretions did not decrease with the administration of oseltamivir when the H5N1 isolate carried this resistance mutation . However, resistance produced by this change may be overcome with higher doses of oseltamivir in vitro, and this change has not been documented to confer resistance to zanamivir .", "Title: Reverse Genetics Approaches for the Development of Influenza Vaccines\nPassage: Killed virus vaccines or IIV are generally administered intramuscularly and can be classified as whole virus vaccines or split vaccines . Whole virus vaccines were the first to be developed. The influenza virus is grown in embryonated chicken eggs, subsequently purified, concentrated and chemically inactivated with formaldehyde . Whole virus vaccines are safe and well tolerated, with an efficacy of 60%-90% in children and adults. On the other hand, the split-virus vaccine exposes all viral proteins and subviral elements upon dissociation of the virions by a nonionic detergent treatment step . Most influenza vaccines in the U.S. and Europe are Title: Confronting Potential Influenza A (H5N1) Pandemic with Better Vaccines", "Passage: To test the hypothesis that whole-virion would be more immunogenic than conventional split-virion or subunit vaccines and may be adaptable to the antigen-sparing strategy, an inactivated, monovalent infl uenza A , whole-virion vaccine was prepared from a highly virulent strain A/Vietnam/1194/2004 strain by removing the polybasic amino acids at the cleavage site, making the virus no longer pathogenic. The seed virus was grown to a high titer in embryonated eggs, inactivated with formalin, and purifi ed. These viruses were then adjuvanted with aluminum hydroxide and used in a phase 1 trial . The highest immune response of 78% seropositivity was Title: Confronting Potential Influenza A (H5N1) Pandemic with Better Vaccines", "Passage: inactivated infl uenza vaccine. This split vaccine induced an antibody response predictive of protection in 54% of healthy adults tested, but only when given intramuscularly at high doses . The large amounts needed means that hundreds of millions of doses are needed to tackle a pandemic. Dose-sparing approaches, including the use of an effi cient nontoxic adjuvant to boost persons' immune responses, may improve the vaccine. Another trial was performed with 300 healthy participants 18-40 years of age, in which aluminum hydroxide adjuvant was used with similar split-virus vaccine . However, the alumadjuvanted vaccines did not improve the immunogenicity or Title: Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein", "Passage: GFP were infected with wild-type CVB3 or CVB3-3A for 30 min at an MOI of 1. At the time points indicated, cells were subjected to titration analysis after freeze-thawing cycles to determine the amount of infectious virus particles. Alternatively, cells were lysed to determine the amount of viral RNA by quantitative PCR. The results are expressed as fold induction relative to the quantities determined directly after removing the inoculum.", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: The continued experience indicating the strong tissue tropism for endothelial cells, specifically, is among the several factors that make \u03b23 integrin an especially attractive candidate as an important in vivo receptor for hantaviruses. It is likely that hantaviruses arrive at their target tissues through uptake by regional lymph nodes, perhaps with or within an escorting lung histiocyte. The virus seeds local endothelium, where the first few infected cells give rise, ultimately, to a primary viremia, a process that appears to take a long time for hantavirus infections . By the time that secondary viremia emerges, the agents of the more Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: Furthermore, antivirals targeting hantaviral receptors have been synthesized. It has been demonstrated that pathogenic hantaviruses attach to the cell surface via host-specific \u03b1 IIb \u03b2 3 or\u03b1 v \u03b2 3 integrins while non-pathogenic hantaviruses initiate cellular entry relying on \u03b1 v \u03b2 1 integrins . Based on the structure of cyclic peptides known to bind the \u03b1 v \u03b2 3 receptor, a few of cyclic peptides or small molecules were designed and screened for their antihantaviral function. The cyclic nonapeptides CLVRNLAWC and CQATTARNC could inhibit SNV and ANDV infection in vitro . After two rounds of biological screening, the peptidomimetic Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: compounds 8012-0652, C481-1256, and G319-0078 were screened out with potency in the nanomolar range against infection of a panel of hantaviruses, including SNV, ANDV, and HTNV . Further studies should be performed to evaluate the safety and efficacy of these small molecules in vivo. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Compared to the human disease, ANDV-infected hamsters exhibit exceptionally high titers of live ANDV in their tissues, with much of the viral replication occurring in hepatocytes, which are spared in the human disease. Titers of live ANDV in some cases exceed 10 8 /g, whereas hantavirus isolates from human tissues have been notoriously difficult to obtain. Despite the universal occurrence of mildly-elevated hepatic enzymes in patients with HCPS, hepatic enzymes do not appear to be present at elevated levels in the blood of diseased hamsters even immediately before death .", "Title: Epidemiology and Virology of Acute Respiratory Infections During the First Year of Life: A Birth Cohort Study in Vietnam\nPassage: No clear seasonal pattern was observed in the overall incidence of ARI presentations; however, there were pathogen-specific seasonal trends . Influenza virus A and RSV infections were highly clustered in the rainy months between July and October 2010, with a second cluster of influenza virus A infections in the dry season between February and May of 2011, whereas other viruses were detected throughout the study period. Title: Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China", "Passage: It has been suggested that most M. pneumoniae epidemics occur in either summer or autumn, with no obvious explanation for this seasonal variation . In this study, M. pneumoniae was prevalent throughout almost the entire year, with peaks occurring in June and September. An epidemiologic study found that influenza viral infection occurred throughout the year with no seasonal predominance . This study showed that influenza viral infection was more prevalent in late autumn and winter. Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: Respiratory syncytial virus is the most important agent to cause acute lower respiratory infection in young children; it also affects older adults and the immunocompromised . RSV infection elicits symptoms ranging from sinusitis and otitis media to bronchiolitis and pneumonia . In temperate climates, outbreaks occur in winter months. Tropical countries also have RSV seasons but with greater variation than in temperate locations . Title: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study", "Passage: defence as several mouse as well as human studies have suggested . The here observed associations were more prominent for LRTIs compared to URTIs, but evident for both, and more pronounced when considering long lasting or frequent RTIs compared to single symptoms. Based on the infection diary data, we generated a RTI diary score summing-up all ten symptoms and allowing to average per month, per whole season or over the whole period of three years. Considering the upper ten percentile of the distribution of such scores as an outcome, associations were typically stronger than when considering single symptoms, and interactions", "Title: Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection\nPassage: rhMBL Binds Both pdmH1N1 and H9N2/GI Viruses A microtiter capture assay demonstrated that MBL could bind to pdmH1N1 and H9N2/G1 in vitro . The MBL-virus binding occurred in a dose-dependent manner . Similarly, increased amount of virus could also result in increased binding by MBL . MBL utilizes the CRD to recognize pathogens in a calcium-dependent manner . Further addition of ethylenediaminetetraacetic acid in the assay inhibited the binding of MBL to both strains of influenza virus , suggesting that the binding occurred through the CRD of MBL. Title: Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection", "Passage: We demonstrated that despite these 2 strains of viruses being bound by rhMBL via the CRD of MBL at the physiological level, they infected both MBL WT and MBL KO mice effectively. Our results are consistent with a recent in vitro study by Job et al , in which MBL was found to bind to pdmH1N1 fairly in vitro but the virus was resistant to the antiviral activity of MBL. The number and position of potential glycosylation sites on the viral HA globular domain determine the binding affinity between MBL and the virus. Even though MBL can physically bind to Title: Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection", "Passage: the virus, the binding may be insufficient for executing any antiviral function. Arguably, Chang et al recently reported that MBL deficiency increases susceptibility to infection with influenza A virus Philippine 82 H3N2 , which is a human strain. We reconcile with the suggestion that MBL effects would differ depending on strains of influenza A virus and thus MBL causes variable antiviral activities and host responses. The degree of glycosylation on the globular head of the HA molecule is believed to be essential for MBL to exhibit its antiviral properties. For Phil82 virus, the high-mannose oligosaccharide at residue 165 of the Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1", "Passage: HIV-1 among South African infants . Mannose-binding lectin is an innate immune receptor synthesised in the liver and secreted in the bloodstream in response to inflammation signal. MBL promotes pathogen elimination by opsonization and phagocytosis, and reduced expression of MBL resulting from polymorphism in coding and non-coding regions has been associated with an increased risk of MTCT of HIV-1 .", "Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo\nPassage: the SN injected with the retrograde virus. One further possibility is that too little virus was used to observe co-labeling of a given region. However, given the density of infection , the latter possibility seems unlikely. Additionally, the spread of the polysynaptic rVSV appears to attenuate with increasing numbers of synapses crossed, permitting an analysis of more restricted viral spread. This is quite fortuitous, as if spread were to continue, it would lead to widespread infection and lethality. In addition, reconstruction of connectivity would be more difficult. This reduced efficiency appears to also hold for the monosynaptic form of VSV Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: the SN injected with the retrograde virus. One further possibility is that too little virus was used to observe co-labeling of a given region. However, given the density of infection , the latter possibility seems unlikely. Additionally, the spread of the polysynaptic rVSV appears to attenuate with increasing numbers of synapses crossed, permitting an analysis of more restricted viral spread. This is quite fortuitous, as if spread were to continue, it would lead to widespread infection and lethality. In addition, reconstruction of connectivity would be more difficult. This reduced efficiency appears to also hold for the monosynaptic form of VSV Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: Recently, we created an anterograde monosynaptic virus that complements the previously available retrograde viral tracers . Vesicular stomatitis virus , a virus related to RABV, with its own glycoprotein gene , or with a G from the unrelated lymphocytic choriomeningitis virus , spreads in the anterograde direction across synapses. VSV can be used as a polysynaptic tracer that spreads across many synapses, owing to the fact that the normal, replicationcompetent form of the virus does not cause serious diseases in humans . Whether the virus is a monosynaptic or polysynaptic tracer is determined by the method of delivery of the Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: Recently, we created an anterograde monosynaptic virus that complements the previously available retrograde viral tracers . Vesicular stomatitis virus , a virus related to RABV, with its own glycoprotein gene , or with a G from the unrelated lymphocytic choriomeningitis virus , spreads in the anterograde direction across synapses. VSV can be used as a polysynaptic tracer that spreads across many synapses, owing to the fact that the normal, replicationcompetent form of the virus does not cause serious diseases in humans . Whether the virus is a monosynaptic or polysynaptic tracer is determined by the method of delivery of the", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: We show that the current strategy for the detection of viral RNA in oral swabs used for 2019-nCoV diagnosis is not perfect. The virus may be present in anal swabs or blood of patients when oral swabs detection negative. In SARS-CoV and MERS-CoV infected patients, intestinal infection was observed at later stages of infection . However, patients infected with 2019-nCoV may harbour the virus in the intestine at the early or late stage of disease. It is also worth to note none of the patients with viremia blood had positive swabs. These patients would likely be considered as 2019-nCoV negative Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: day 0. However, this trend appears to change on day 5. We found more anal swab positive than oral swab positive . Another observation is the reoccurrence of virus in 6 patients who were detected negative on day 0. Of note, 4 of these 6 viral positives were from anal swabs . These data suggested a shift from more oral positive during early period to more anal positive during later period might happen. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral\u2013fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: In the first investigation, we aimed to test whether viral positive can be found in anal swab and blood as well as oral swabs. We conducted a molecular investigation to patients in Wuhan pulmonary hospital, who were detected as oral swabs positive for 2019-nCoV upon admission. We collected blood, oral swabs and anal swabs for 2019-nCoV qPCR test using previously established method .", "Title: Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection\nPassage: The pharmacological induction of IFITM3 could represent a broad-spectrum therapeutic treatment for a range of pathogenic agents. Although injection of type I IFN can induce IFITM3 and other antiviral responses, undesirable off target effects associated with this type of therapy limit its current clinical use. More refined approaches triggering the specific induction of antiviral proteins independently of IFN will provide antiviral resistance with minimal side effects. Here we show that IFITM3 can be up-regulated on T cells independent of IFN signalling. If defined and harnessed, this non-IFN pathway of IFITM3 induction could be targeted as an antiviral therapeutic approach providing Title: Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection", "Passage: While some cell types, including respiratory epithelial cells and tissue resident memory T cells constitutively express IFITM3, many others do not express this antiviral protein in steady-state conditions and only upregulate expression after exposure to type I or type II interferons . Expression levels of IFITM3 are tightly regulated by the E3 ubiquitin ligase, NEDD4, which reduces baseline levels of IFITM3 by ubiquitinating the antiviral protein, thereby promoting its turnover . Title: Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection\nPassage: the coveted antiviral actions of IFITM3 while avoiding the undesirable, pleiotropic effects of interferon treatment. Title: Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection", "Passage: Whether IFITM3 expression is regulated differently in distinct cell types remains unclear. As immune cells often carry out effector functions at sites of infection and are therefore directly exposed to virus-infected cells, these cells are likely to benefit greatly from regulated expression of antiviral proteins. We have previously reported that dendritic cells stationed within the lung upregulate IFITM3 following influenza virus infection, a process driven by exposure to type I interferon, and this was crucial for these cells to successfully traffic influenza viral antigen from the lung to draining lymph node without becoming infected and perishing en route . Tissue", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: work became the basis for construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires . Using hybrid M13 phage displaying Co 3 O 4 -and gold-binding peptides on pVIII as a scaffold to assemble nanowires on polyelectrolyte multilayers, Nam et al. produced a thin, flexible lithium ion battery, which could be stamped onto platinum microband current collectors . The electrochemical properties of such batteries were further improved through pIII-display of single-walled carbon nanotube-binding peptides , offering an approach for sustainable production of nanostructured electrodes from poorly conductive starting materials. Phagebased nanomaterials have found applications in cancer imaging Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: work became the basis for construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires . Using hybrid M13 phage displaying Co 3 O 4 -and gold-binding peptides on pVIII as a scaffold to assemble nanowires on polyelectrolyte multilayers, Nam et al. produced a thin, flexible lithium ion battery, which could be stamped onto platinum microband current collectors . The electrochemical properties of such batteries were further improved through pIII-display of single-walled carbon nanotube-binding peptides , offering an approach for sustainable production of nanostructured electrodes from poorly conductive starting materials. Phagebased nanomaterials have found applications in cancer imaging Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For more than a decade, interest in the filamentous phage as a building block for nanomaterials has been growing because of its unique physicochemical properties, with emerging applications in magnetics, optics, and electronics. It has long been known that above a certain concentration threshold, phage can form ordered crystalline suspensions . Lee et al. engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields. Taking advantage of the ability to display substrate-specific peptides at known locations on Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For more than a decade, interest in the filamentous phage as a building block for nanomaterials has been growing because of its unique physicochemical properties, with emerging applications in magnetics, optics, and electronics. It has long been known that above a certain concentration threshold, phage can form ordered crystalline suspensions . Lee et al. engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields. Taking advantage of the ability to display substrate-specific peptides at known locations on", "Title: Temporal trends in the discovery of human viruses\nPassage: A standard method for estimating numbers of species is to extrapolate the cumulative species discovery curve . We gathered data for this curve by systematically searching the primary literature for first reports of human infection with each of the currently recognized virus species, using species as defined by the International Committee on Taxonomy of Viruses . We note that the set of viruses we are interested in-those that can infect humans-is a small subset of the total and, as is discussed below, not a closed set because many of these viruses can also infect other hosts . We regard this Title: Estimating the number of infections and the impact of non-\nPassage: before testing became widespread. Title: Temporal trends in the discovery of human viruses", "Passage: before testing became widespread. Title: Temporal trends in the discovery of human viruses\nPassage: From a comprehensive search of the primary literature, we found 188 virus species that have been reported to infect humans, going back to yellow fever virus in 1901 . Since then, the number of human virus species discovered in any given year has ranged from zero to six. As is typical , the cumulative species discovery curve increases slowly initially and then more rapidly . Piecewise linear regression suggests no further upswings since 1954, roughly corresponding to the advent of tissue culture techniques for virus detection . Title: Early Days of Food and Environmental Virology", "Passage: We began by trying to obtain suitable human placentas for culture, from the obstetrical facility at the Chicago Lying-in Hospital, which was part of the UC Medical School. After several culture failures, I was told that these placentas were inevitably slathered with tincture of green soap. Colleagues on the medical school faculty had already cornered the supply of ''clean'' placentas from voluntary hysterectomies. The alternative was monkey kidney. Dr. Bergdoll maintained a colony of approximately 100 rhesus monkeys , which were used in detecting staphylococcal enterotoxins and determining the mode of enterotoxin pathogenesis. After a few experiments, an animal would", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America", "Passage: Turkey 77% of the first 111 confirmed cases in the Turkish community were imported . In Ireland 84% of the first 156 cases were imported, 14 were infected in Ireland by an imported case and two were infected in Ireland without any identifiable travel association . Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America\nPassage: There was a marked difference in the proportion of imported cases in Victoria and WA. In WA 50 of the first 102 cases had travelled and a further 20 were directly linked to those cases that had travelled interstate. This is similar to the experiences of countries in the northern hemisphere. For example, in Spain 78% of the first 98 cases had acquired their infection abroad ; in the United Kingdom 44% of the first 65 cases reported travel to the United States or Mexico ; in Germany 47% of the first 198 cases were described as imported and in", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America", "Passage: traveller returned from the US. All five cases were reported on 20-21 May. Two cases diagnosed on 1 June were reported to have travelled to an affected country in the seven days prior to illness onset although the country was not specified for either case. One other case diagnosed on 2 June, was reported to have acquired her infection in Japan. Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America\nPassage: unlikely, given widespread media attention and active case-finding at that time that targeted travellers reporting influenza-like illness. Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America", "Passage: The most likely explanation for the discrepancy between the way the novel virus was detected in Mexico and the US is that the virus had been circulating far longer in Mexico than the US. One phylogenetic analysis suggests that the pandemic virus may have entered the human population between November 2008 and March 2009 while a second study suggests the virus may have been causing human infections as early as September 2008 . Widespread unrecognised community transmission causing mild infections may have been occurring in Mexico for some weeks or months, eventually leading to recognition of a cluster of severe", "Title: Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks\nPassage: t-test was carried out to calculate the statistical significance. enrichment was determined using two-tailed unequal variances t-test. Proteins were filtered according to their annotations with traffic-related gene ontology terms . DOI: 10.7554/eLife.23172.022 Title: Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment", "Passage: shows that, as the day progresses, the connectivity between individuals increases, peaking at mid-day and late afternoon and decreasing again in the evening, when people return back home. This time-varying and recurrent pattern of human mobility and co-location can be quantitatively described by three network metrics: the size of the largest component, the number of components and the average shortest path of N P at every time slice . Whereas the average shortest path of N P remained fairly constant over time the temporal pattern in the size of the largest component and number of components showed significant temporal heterogeneities. Title: Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks", "Passage: SCC FAK-WT/SCC FAK -/-ratios were log 2 -transformed. The significance of enrichment was determined using two-tailed unequal variances t-test. Proteins were filtered according to their annotations with traffic-related gene ontology terms . DOI: 10.7554/eLife.23172.024 Title: Comparison of Road Traffic Injury Characteristics between Local versus Floating Migrant Patients in a Tertiary Hospital between 2007 and 2010\nPassage: was unclear before.", "Title: Is the risk of multiple sclerosis related to the \u2018biography\u2019 of the immune system?\nPassage: The IgG-anti-EBNA1 antibody concentrations are particularly elevated in patients with MS , and systematic studies on the T-helper cell epitopes in the EBNA1 protein revealed that CD4 ? T-cells from healthy EBV carriers matched for MS-associated HLA-DR alleles recognised several epitopes within the central region of the C-terminal domain of this protein but not other EBVencoded proteins . In contrast, those from MS patients recognised many more epitopes spread over the entire domain . Concomitantly, the number of memory T-cells directed against this domain is increased about tenfold in MS and have been shown to be T-helper 1 cell precursors Title: Is the risk of multiple sclerosis related to the \u2018biography\u2019 of the immune system?", "Passage: and polarised effector memory cells , containing a subfraction of regulatory T-cells . T reg s were suppressed in MS , and high level of CD8 ? T-cell activation against EBV but not cytomegalovirus was demonstrated early in the course of MS . Title: Is the risk of multiple sclerosis related to the \u2018biography\u2019 of the immune system?", "Passage: Enhanced immune reactivity in MS patients in comparison with healthy control subjects as identified by systematic studies ; consensus in other proteins to the EBV sequence given by * for identical amino acid, ? for similar amino acid , and / for missing amino acid; one additional homology in vaccinia virus regulation within the cells via reduced levels of glutathione peroxidase . In MS there is still another environmental risk factor, namely, suboptimal levels of bio-active vitamin D , which, as demonstrated in rat astrocytes, may impair via c-glutamyl transpeptidase intra-cellular glutathione levels . Table 3 MS-associated pathogens and homologies Title: The Way Forward: Potentiating Protective Immunity to Novel and Pandemic Influenza Through Engagement of Memory CD4 T Cells", "Passage: node is not clear at the moment. There are efforts to sample these sites of the germinal center response in situ, using such methods as fine-needle aspiration . These approaches would permit much more precise insight into the evolution of the germinal center response over time, including a detailed understanding of the responding B-cell and CD4 T-cell receptor repertoire.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: work became the basis for construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires . Using hybrid M13 phage displaying Co 3 O 4 -and gold-binding peptides on pVIII as a scaffold to assemble nanowires on polyelectrolyte multilayers, Nam et al. produced a thin, flexible lithium ion battery, which could be stamped onto platinum microband current collectors . The electrochemical properties of such batteries were further improved through pIII-display of single-walled carbon nanotube-binding peptides , offering an approach for sustainable production of nanostructured electrodes from poorly conductive starting materials. Phagebased nanomaterials have found applications in cancer imaging Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: work became the basis for construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires . Using hybrid M13 phage displaying Co 3 O 4 -and gold-binding peptides on pVIII as a scaffold to assemble nanowires on polyelectrolyte multilayers, Nam et al. produced a thin, flexible lithium ion battery, which could be stamped onto platinum microband current collectors . The electrochemical properties of such batteries were further improved through pIII-display of single-walled carbon nanotube-binding peptides , offering an approach for sustainable production of nanostructured electrodes from poorly conductive starting materials. Phagebased nanomaterials have found applications in cancer imaging Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For more than a decade, interest in the filamentous phage as a building block for nanomaterials has been growing because of its unique physicochemical properties, with emerging applications in magnetics, optics, and electronics. It has long been known that above a certain concentration threshold, phage can form ordered crystalline suspensions . Lee et al. engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields. Taking advantage of the ability to display substrate-specific peptides at known locations on Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For more than a decade, interest in the filamentous phage as a building block for nanomaterials has been growing because of its unique physicochemical properties, with emerging applications in magnetics, optics, and electronics. It has long been known that above a certain concentration threshold, phage can form ordered crystalline suspensions . Lee et al. engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields. Taking advantage of the ability to display substrate-specific peptides at known locations on", "Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: A reason for this could be that very young children have limited contact to others reducing thereby the chance for a co-infection, whereas children older than 3 years already established immunity to an increasing number of viruses encountered previously. Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus", "Passage: RTIs are a major cause of morbidity and mortality worldwide. Acute RTI is most common in children under five years of age, and represents 30-50% of the paediatric medical admissions, as well as 20-40% of hospitalizations in children. Respiratory infections cluster during winter and early spring months. The leading viral agents include respiratory syncytial virus , influenza A and B viruses, parainfluenza viruses , and human adenoviruses . In addition, there is a continuously increasing list of new respiratory viruses that contribute significantly to the burden of acute respiratory infections, such as the recently identified human metapneumovirus and human Bocavirus Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: Respiratory syncytial virus is the most important agent to cause acute lower respiratory infection in young children; it also affects older adults and the immunocompromised . RSV infection elicits symptoms ranging from sinusitis and otitis media to bronchiolitis and pneumonia . In temperate climates, outbreaks occur in winter months. Tropical countries also have RSV seasons but with greater variation than in temperate locations . Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus", "Passage: Text: Viral Respiratory tract infections represent a major public health problem because of their world-wide occurrence, ease of transmission and considerable morbidity and mortality effecting people of all ages. Children are on average infected two to three times more frequently than adults, with acute RTIs being the most common infection in childhood . Illnesses caused by respiratory viruses include, among others, common colds, pharyngitis, croup, bronchiolitis, viral pneumonia and otitis media. Rapid diagnosis is important not only for timely therapeutic intervention but also for the identification of a beginning influenza epidemic and the avoidance of unnecessary antibiotic treatment .", "Title: First Complete Genome Sequence of a French Bovine coronavirus Strain\nPassage: M, and N genes of the obtained BCoV were submitted to a Blastn analysis. According to these analyses, the orf1ab gene is closely related to the Dromedary camel coronavirus HKU23-23-362F strain from the United Arab Emirates , with a nucleotide identity of 99.19%. Conversely, the NS2, HE, S, ns5, and M genes are closely related to the BCoV Bubalus/Italy/179/07-11 strain , with nucleotide identities of 99.88%, 99.45%, 99.02%, 98.79%, and 99.28%, respectively. The E gene is closely related to the Chinese Bovine coronavirus strain BCV-AKS-01 , with a nucleotide identity of 100%. Finally, the highest Blastn score for the N Title: Genomic Characterization and High Prevalence of Bocaviruses in Swine", "Passage: Using an open reading frame finder , three ORF were found in both genomes . The ORFs of PBoV1-H18 were 636 aa for NS1, 219 aa for NP1 and 621 aa for VP1/VP2. The ORFs of PBoV2-A6 were 703 aa for NS1, 221 aa for NP1 and 704 aa for VP1/VP2. The possible splicing of bocavirus NS1 transcripts recently shown to extend the length of NS1 proteins was not investigated here . Title: Discovery and Genomic Characterization of a Novel Ovine Partetravirus and a New Genotype of Bovine Partetravirus", "Passage: larger than the Similar to other partetraviruses, there exists a putative third ORF in a different reading frame within the VP1u region for both bovine partetravirus HK5 and ovine parvovirus. In agreement with previous studies, the phospholipase A 2 motifs of ORF2 are found in the VP1u region, which is also the most conserved region among partetraviruses . The putative third ORF encodes a small protein containing a single transmembrane helix spanning 20 aa in the centre, with predicted molecular weights of 9.5 kDa in bovine partetravirus HK5 and 9.7 kDa in ovine parvovirus. The aa sequences of this putative Title: First Complete Genome Sequence of a French Bovine coronavirus Strain", "Passage: Multiple-sequence alignment, including 20 BCoVs and 10 clade A betacoronaviruses closely related to BCoV from North America, two DcCoVs from the United Arab Emirates, and two Human coronavirus OC43 strains from France, was performed using the Muscle algorithm implemented in MEGA7 . The phylogenetic analysis on the orf1ab confirms that BCoV/FRA-EPI/CAEN/2014/13 is closely related to the Dromedary camel coronavirus HKU23-23-362F. The orf1ab gene of these two viruses together clustered separately from that of BCoV and BCoV-like viruses from North America and Asia. This finding also confirms the results from our previous analysis on partial genomes in which nsp12, S, and", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Since that first report, a slow discovery process over the following two to three years revealed a virus that had infected over 90 % of adult dromedary camels in the KSA , also DCs across the Arabian Peninsula and parts of Africa that are a source of DC imports for the KSA . To date, MERS-CoV has not been detected in DCs tested in zoos or herds from other parts of the world . Occasionally, virus is transmitted from infected DCs to exposed humans. Subsequent transmission to other humans requires relatively close and prolonged exposure . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Since this study, a host of peer-reviewed reports have looked at both DCs and other animals, and the possibility that they may host MERS-CoV infection. Seropositive DCs have been found throughout the Arabian Peninsula including Oman, the KSA, Qatar, Jordan, the United Arab Emirates , Kuwait as well as Sudan, Somalia, Egypt, Tunisia, Nigeria, Kenya and Ethiopia in Africa and the Canary Islands . Other animals tested include sheep, cows, pigs, horses, donkeys, mules, birds, water buffalo, goats, Bactrian camels, llamas and guanaco but none had detectable neutralising antibody against MERS-CoV . No virology or serology studies of human samples Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: DCs, may be an occupational group with significantly higher incidence of seropositivity to MERS-CoV when animals have active MERS-CoV infections . Expanded virological investigations of African DCs may lead to more seropositive animals and geographic areas in which humans may be at risk. It is possible that there are areas where humans already harbour MERS-CoV infections that have not been identified because of an absence of laboratory surveillance. Virological investigations of bats may lead to findings of ancestral viruses and viral 'missing links' and identifying any other animal sources of zoonotic spread is important to inform options for reducing human Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: decades . Older sera have not been tested and so precisely how long DCs have been afflicted by MERS-CoV, whether the virus is enzootic among them, introduced to them decades or centuries ago from bats in Africa or the Arabian Peninsula, or they are the subject of regular but short-lived viral incursions from an as yet unknown host, cannot be answered.", "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: Data on viral shedding dynamics could help in assessing duration of infectiousness. For severe acute respiratory syndrome-related coronavirus , infectivity peaked at around 10 days after illness onset , consistent with the peak in viral load at around that time . This allowed control of the SARS epidemic through prompt detection of cases and strict isolation. For influenza virus infections, virus shedding is highest on the day of illness onset and relatively higher from shortly before symptom onset until a few days after onset . To date, transmission patterns of 2019-nCoV appear more similar to influenza, with contagiousness occurring around Title: Estimating the number of infections and the impact of non-", "Passage: countries between 7 and 43 million individuals have been infected with SARS-CoV-Z up to 28th March, Title: Breaking the Waves: Modelling the Potential Impact of Public Health Measures to Defer the Epidemic Peak of Novel Influenza A/H1N1\nPassage: An example for the prevalence of symptomatic cases resulting from our SEIR model is shown in Figure S2 for three different values of R0 . For an R0 of 1.58 the point estimate of the timing of the peak after introduction of the first case would be 10 to 11 weeks , the point estimate for the peak prevalence of the population infected would be 4.3%, for the total attack rate of the population infected 44.8% and for the population diseased 38.5% . Depending on the three R0 the cumulative proportions of children that develop symptoms are 48%, 67%, and Title: Breaking the Waves: Modelling the Potential Impact of Public Health Measures to Defer the Epidemic Peak of Novel Influenza A/H1N1", "Passage: 79%, and the cumulative proportion of symptomatic adults 17%, 34%, and 54%, respectively. As a result of the higher susceptibility of children in the model the peak proportion of infected children is reached 18, 12 or 8 weeks after the first infected case, roughly 1-1.5 weeks earlier than in adults . Figure S3 shows how the peak is delayed for an assumed R0 of 1.58 and 5 imported cases per day when the first 500 cases are managed with a combination of intensive case-based measures , followed by 10,000 with management mainly restricted to members of the household . The", "Title: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events", "Passage: Moreover, we observed a highly significant repression of 2-hydroxyphytanoyl-CoA-lyase. This peroxisomal thiamine pyrophosphate-dependent enzyme is rate limiting in the breakdown of 2-hydroxy fatty acids. The biological role of 2-hydroxy fatty acids has only recently become apparent and cumulative evidence suggests intermediates of energy metabolism to specifically activate G-protein coupled receptors which are now classified as hydroxy carboxylic acid receptors . The HCA2 receptor is involved in a complex negative feed-back loop whereby ketone bodies derived from fatty acid oxidation are sensed by HCA2 via the activity of 3-hydroxybutyrate that leads to inhibition of lipolysis and to restriction of further fatty Title: Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism", "Passage: Intramuscular fat is an indispensable energy source for skeletal muscle. These lipids play pivotal roles in metabolism not only for skeletal muscle but also for the entire body. The status of the endoplasmic reticulum is a significant determinant of protein homeostasis in muscle cells. Accumulation of unfolded proteins and other physiological stresses produces ER stress, which initiates the unfolded protein response . More importantly, the signaling pathway activated by the ER stress has emerged as a critical regulator of lipid biosynthesis, insulin resistance, inflammation, and apoptosis . Title: Angiotensin-converting enzyme 2/angiotensin-(1\u20137)/Mas axis activates Akt signaling to ameliorate hepatic steatosis", "Passage: Multiple metabolic pathways lead to the development of hepatic steatosis, including increased lipogenesis and lipolysis, and decreased fatty acid oxidation 21 . Key transcriptional regulators such as LXR\u03b1 and SREBP-1c coordinately control lipogenesis 22 . LXR\u03b1 and SREBP-1c increase the expression of key lipogenic genes, including those for FAS, SCD1 and ACC 23 . ACC1 converts acetyl-CoA to malonyl-CoA, and inhibits fatty acid entry into the mitochondria reducing \u03b2 -oxidation. FAS utilizes both acetyl-CoA and malonyl-CoA to form palmitic acid . Besides, adiponectin appears to have a pivotal role in improving fatty acid oxidation and decreasing fatty acid synthesis 24 Title: Polyphenol-Rich Extracts from Toona sinensis Bark and Fruit Ameliorate Free Fatty Acid-Induced Lipogenesis through AMPK and LC3 Pathways", "Passage: The human hepatoma cell line HepG2 was used to mimic FFA-induced steatosis in the human body . Oleic and palmitic acids are the most abundant FFAs in patients with steatosis . A lipidladen HepG2 cell model was established by adding different FFA levels for 24 h. As shown in Figure 1 , FFA induced lipid accumulation in a concentrationdependent manner (Figure 2A", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Tuberculosis care for pregnant women: a systematic review\nPassage: generalise the conclusions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: Host resilience to emerging coronaviruses", "Passage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\". Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5", "Title: Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus\nPassage: Ethics statement and animals used. The methods used in the present study were approved by the Iowa State University IACUC . Fayoumi and Leghorn chicken lines from Iowa State University Poultry Farm were used in this study. The Fayoumis and Leghorns each have an inbreeding coefficient of \u03fe99.9%, as determined by microsatellites , and 99.95%, as determined by resequencing . The Fayoumi line originated from the Fayoum region of Egypt, whereas the Leghorn line is representative of chickens from the U.S. egg-laying industry of the 1950s. The chickens were given ad libitum access to water and feed throughout the study. Title: Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus", "Passage: are significantly different . At 2 dpi, data are for 21 Fayoumi and 28 Leghorn chickens, and at 6 dpi, data are for 12 Fayoumi and 20 Leghorn chickens . The antibody titer is displayed as the least-square means of the S/P ratio in the Fayoumis and Leghorns at 10 dpi, and the error bars represent standard deviations. The connecting letters report was generated by Student's t test. At 10 dpi, data are for 8 challenged Fayoumi chickens, 13 challenged Leghorn chickens, 6 nonchallenged Fayoumi chickens, and 8 nonchallenged Leghorn chickens . significant difference between the lines within the same Title: Association of Candidate Genes with Response to Heat and Newcastle Disease Virus", "Passage: Pooled semen from 16 sires was used to inseminate 145 dams to produce three hatches of 360 mixed-sex chicks of a commercial brown egg layer line for this study. Birds were provided ad libitum access to feed and water throughout the study period and were reared following standard commercial husbandry practices. Initially, 23 h of light was provided, which was gradually decreased to 13.5 h of light by day 29. The birds were reared at thermo-neutral temperature . In each of the three replicates , half of the chicks were ground transported from Hy-Line International in Dallas Center, IA, USA Title: Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds\nPassage: BF2, the chickens were divided into two groups based on time between inoculation and death: early phase and late phase . Odds ratios and 95% confidence intervals were calculated by logistic regression analysis.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The first validated diagnostic test was designed in Germany. Corman et al. had initially designed a candidate diagnostic RT-PCR assay based on the SARS or SARS-related coronavirus as it was suggested that circulating virus was SARS-like. Upon the release of the sequence, assays were selected based on the match against 2019-nCoV upon inspection of the sequence alignment. Two assays were used for the RNA dependent RNA polymerase gene and E gene where E gene assay acts as the first-line screening tool and RdRp gene assay as the confirmatory testing. All assays were highly sensitive and specific in that they did Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The existing practices in detecting genetic material of coronaviruses such as SARS-CoV and MERS-CoV include reverse transcription-polymerase chain reaction , real-time RT-PCR , reverse transcription loop-mediated isothermal amplification and real-time RT-LAMP . Nucleic amplification tests are usually preferred as in the case of MERS-CoV diagnosis as it has the highest sensitivity at the earliest time point in the acute phase of infection . Chinese health authorities have recently posted the full genome of 2019-nCoV in the GenBank and in GISAID portal to facilitate in the detection of the virus . Several laboratory assays have been developed to detect the novel Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: In addition, there are seven potential rapid diagnostic kits available on the market for 2019-nCoV. Six of these are only for research purposes. Only one kit from Beijing Genome Institute is approved for use in the clinical setting for rapid diagnosis. Most of the kits are for RT-PCR. There were two kits with the capability to detect multiple pathogens using sequencing and microarray technologies, respectively. The limit of detection of the enhanced realtime PCR method was 10 2 -fold higher than the standard real-time PCR assay and 10 7fold higher than conventional PCR methods In the clinical aspect, the enhanced Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The Hong Kong University used two monoplex assays which were reactive with coronaviruses under the subgenus Sarbecovirus . Viral RNA extracted from SARS-CoV can be used as the positive control for the suggested protocol assuming that SARS has been eradicated. It is proposed that the N gene RT-PCR can be used as a screening assay while the Orf1b assay acts as a confirmatory test. However, this protocol has only been evaluated with a panel of controls with the only positive control SARS-CoV RNA. Synthetic oligonucleotide positive control or 2019-nCoV have yet to be tested .", "Title: SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models\nPassage: solving urgent biological problems, including the development of strategies to combat emerging or reemerging biothreats, such as the severe acute respiratory syndrome virus , the 2009 H1N1 influenza virus , and the 2011 German Escherichia coli outbreak . Title: Virus Adaptation by Manipulation of Host's Gene Expression", "Passage: The viral load reached by replicating TEV populations in A. thaliana was estimated by the dilution-inoculation assay method on the local-lesion host Chenopodium quinoa . In short, 2 g of tissue was ground in 1 mL of 0.5 M phosphate buffer. Four different leafs from each one of three different 4-week-old C. quinoa plants were rub-inoculated with 5 mL of undiluted, 5-and 10-fold diluted virus, respectively; 100 mg/mL carborundum were added to facilitate inoculation. Nine dpi, the number of local lesions was recorded and transformed into viral infectious loads by estimating the intercept of the regression line of the observed Title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity", "Passage: 0.1% penicillinstreptomycin and incubated in 7% CO 2 at 37uC. Cells and supernatant containing SeV 52 and rDPs were harvested after 48 h and 200 ml of the suspension were inoculated in the allantoic cavity of 10-day embryonated hen eggs . After 40 h allantoic fluid was harvest and 200 ml of undiluted fluid were inoculate in 10-day embryonated eggs for virus growth and egg inoculation was repeated for three consecutive passages. Allantoic fluid from the third passage was quick-frozen in dried ice/ethanol and used for infections. Presence of recombinant DVG was confirmed by PCR. No other DVGs were detected. Title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity", "Passage: To further investigate the cellular mechanisms responsible for the efficient activation of the antiviral response by SeV DVGs, we evaluated the phosphorylation of transcription factors that are critical for the expression of type I IFNs in cells infected with equivalent amounts of infectious particles of a SeV strain Cantell stock containing high levels of copy-back DVGs or with SeV Cantell depleted of DVGs . Virus stocks were prepared from the same parental virus and their content of DVGs was determined by calculating the ratio of infectious particles to total particles . In addition, copy-back DVGs of these stocks were identified", "Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial\nPassage: Nigeria yielded incidence rates up to approximately 20 per 100 PY, with the highest rates in the 3-through 5-and 9through 11-month age groups . In Kenya, the incidence of RSV-associated LRTI was highest in infants aged 0-5 months , with incidences of 5.9 to 8.8 per 100 PY in children aged 6-30 months . A study in India reported a more uniform distribution of RSV-associated ALRI across age groups . Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: A review of the global burden of RSV estimates an annual incidence of approximately 34 million episodes of ALRI associated with RSV infection in children aged <5 years . Just over 3 million episodes were estimated to result in hospitalization and between 66 000 and 199 000 in death . Most deaths occur in the developing world . Infants have consistently higher rates of RSV-associated illness and hospitalization than older children in both industrialized and developing nations . Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: This compares with RSV-associated LRTI hospitalization of 1 per 100 PY in Kenya . However, surprisingly few pneumonia cases were observed in our study. A recent review of pneumonia worldwide estimated the number of new episodes of RSV-associated pneumonia in children aged 0-4 years to be 17 778 in Australia, 431 938 in Brazil, 140 879 in Colombia, 10 724 in Costa Rica, 320 132 in Mexico, 700 364 in the Philippines, 3126 in Singapore, and 186 889 in Thailand, although the incidence rate was not calculated . Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: The overall incidence of RSV-associated ILI in the study population was 7.0 per 100 PY. The highest incidence occurred in children aged 12-23 and 24-35 months in all countries except the Philippines, where the incidence was highest in the youngest age group, and in Mexico, where it was similar in children aged 6-11, 12-23, and 24-35 months . The Philippines had the highest incidence of RSVassociated ILI , followed by Brazil, Singapore, and Australia ; lower incidences were recorded for Colombia, Costa Rica, Mexico, and Thailand . The occurrence of RSV at different times of the year was highly variable", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Text: The emergence and outbreak of a newly discovered acute respiratory disease in Wuhan, China, has affected greater than 40,000 people, and killed more than 1,000 as of Feb. 10, 2020. A new human coronavirus, SARS-CoV-2, was quickly identified, and the associated disease is now referred to as coronavirus disease discovered in 2019 . Title: CDC Summary 21 MAR 2020,\nPassage: CDC is responding to a pandemic of respiratory disease spreading from person-to-person caused by a novel coronavirus. The disease has been named \u201ccoronavirus disease 2019\u201d . This situation poses a serious public health risk. The federal government is working closely with state, local, tribal, and territorial partners, as well as public health partners, to respond to this situation. COVID-19 can cause mild to severe illness; most severe illness occurs in older adults. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region .", "Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts\nPassage: During the past half-century, medical advances have led to an increase in the world's population of immunosuppressed individuals. This includes those receiving immunosuppressive therapies, those with acquired immunosuppressive diseases such as the 34 million worldwide with human immunodeficiency virus and AIDS , and individuals living longer with any of the over 150 known primary immunodeficiencies . The most severely immunocompromised are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who receive other immunosuppressive therapies such as chemotherapy and/or solid organ or stem cell transplants. Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts", "Passage: Eighty-six influenza patients were enrolled over a 3-year period between 2008 and 2011. Of these, 32 were classified as severely immunocompromised, primarily due to a malignancy or condition being treated with either a recent HSCT or immunosuppressive therapy. The remaining 54 patients were classified as nonimmunocompromised and included individuals both with and without underlying comorbidities. The demographics of these individuals are summarized in Table 2 . Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts\nPassage: the inability of the host to respond. This may require reconsidering prevention of disease as our goal and shifting our focus to reducing severe disease and complications such as the prolonged shedding and severe illness observed in the immunocompromised patients in this study. Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts", "Passage: Of note, 46.5% of the individuals in the study had been vaccinated within 1 year of becoming infected with influenza. A majority of the nonimmunocompromised individuals were overweight or obese . Although most patients in the study were nonsmokers, 22.2% of nonimmunocompromised participants were current smokers, whereas there were no current smokers in the immunocompromised group.", "Title: Host and viral traits predict zoonotic spillover from mammals\nPassage: highest for Bunya-, Flavi-and Arenaviruses in rodents; Flavi-, Bunyaand Rhabdoviruses in bats; and Herpesviruses in non-human primates . Of 586 mammalian viruses in our dataset, 263 have been detected in humans, 75 of which are exclusively human and 188 zoonotic-defined operationally here as viruses detected at least once in humans and at least once in another mammal species . The proportion of zoonotic viruses is higher for RNA than DNA viruses. The observed number of viruses per wild host species was comparable when averaged across orders, but bats, primates, and rodents had a higher proportion of observed zoonotic viruses compared Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: In examining the raw data, we found that observed viral richness within mammals varies at a host order and viral family level, and is highest for Bunya-, Flavi-, and Arenaviruses in rodents; Flavi-, Bunya-, and Rhabdoviruses in bats; and Herpesviruses in non-human primates . Of 586 mammalian viruses in our dataset, 263 have been detected in humans, 75 of which are exclusively human and 188 zoonotic -defined operationally here as viruses detected at least once in humans and at least once in another mammal species . The proportion of zoonotic viruses is higher for RNA than DNA viruses. The observed Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: of 586 unique viruses published in the literature between 1940-2015 initially by using the virus name and synonyms as the search keywords in the major online reference databases in addition to searching in books, reviews, and literature cited in sources we had already obtained. To narrow the search for hosts for well-researched viruses, we additionally included the terms \"host\", \"reservoir\", \"wildlife\", \"animals\", \"surveillance\", and other relevant terms to find publications related to host range. Associations were cross-checked for completeness with the Global Mammal Parasite Database for primate, carnivore and ungulate viruses, version as of Nov 2006 30 and other published Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: publications related to host range. Associations were cross-checked for completeness with the Global Mammal Parasite Database for primate, carnivore and ungulate viruses, version as of Nov 2006 29 and other published reviews specific to bats and rodents 12, 30, 31 . We excluded all records without species-level host information, and those where we could not track down the primary references. Records of mammal-virus associations from experimental infection studies, zoological parks or captive breeding facilities, or cell culture discoveries were excluded. Host species were defined as domestic or wild following the list of domestic animal species from the Food and Agriculture", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Text: Coronaviruses are spherical, enveloped, and the largest of positive-strand RNA viruses. They have a wide host range, including birds, farm animals, pets, camels, and bats, in which they primarily cause respiratory and gastrointestinal disease. Belonging to the order Nidovirales, family Coronaviridae, and the subfamily Orthocoronaviridae there are four genera of coronaviruses-Alphacoronavirus, Betacoronavirus, Deltacorona virus, and Gammacoronavirus . Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000", "Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice\nPassage: potent immune responses that are minimally affected by pre-existing immunity . Hexon-chimeric adenoviruses can also avoid neutralization . Both approaches offer promise in the context of addressing pre-existing immunity, but require further investigation in response to concerns regarding safety and feasibility of largescale production. Covalent attachment of polyethylene glycol or incorporation of the virus into polymer matricies can also effectively protect Ad5 from neutralization . Delivery of Ad5-based vaccines by mucosal routes can also circumvent the effect of pre-existing immunity and induce a significant immune response against an encoded antigen . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: serotypes such as adenovirus types 3, 7, 11, and 35 can evade anti-Ad5 immune responses while maintaining effective antigen delivery and immunogenicity . Prime-boost strategies, using DNA or protein immunization in conjunction with an adenovirus vaccine booster immunization have also been explored as a means to avoided preexisting immunity . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: both CD4 + and CD8 + T cell responses . The adenovirus vector is another of the most widely evaluated vectors to date to express heterologous antigens, due to ease of production, safety profile, genetic stability, the ease of DNA genome manipulation, and the ability to stimulate both innate and adaptive immune responses and induce both T and B cell responses . They have been extensively examined as a delivery vector in several preclinical and clinical studies for infectious diseases such as anthrax, hepatitis B, human immunodeficiency virus -1, influenza, measles, severe acute respiratory syndrome , malaria and tuberculosis M. Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: Taken together, these data support the notion that the exposition of the virus capsid proteins facilitates the immune response against the encoded antigen. Optimization of PEGylation chemistries and/or densities on adenovirus-based vaccine that promote and strengthen protective immune responses following oral immunization is currently underway.", "Title: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey\nPassage: Among our cohort of 215 children, 57% were male. The median age of the patients was 31 months , with 19% of the children having less than 3 months of age . As shown in Table 1 , 101/215 children presented with one or more underlying co-morbid condition, principally chronic lung diseases and neurological disorders. The median age of patients presenting co-morbidities was significantly higher than of those without . Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: 68.8 % males: mean age was 53.2 years , and 31.2 % females: mean age was 53.2 years , where the youngest patient reported was 10 month and the oldest patient reported was 109 year old. Comorbidities were reported in 46.9 %: mean age was 60.1 and 71.8 % male and 28.2 % female. Healthcare workers were reported to be 15.6 %, mean age was 38.6 and 53.3 % male, 46.7 % female and 19.7 % of them had comorbidities. 12.1 % reported with history of camel contact; mean age was 56.7 and 91.7 % male, 8.3 % female and Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years . Title: Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People\u2019s Republic of China\nPassage: reported in the first two waves and 1 death in a case-patient less than 15 years of age was reported in the third wave. Among cases who died, the median age was 66.5, 63.0 and 58.5 years in each of the three waves, respectively. The median age of death in the third wave was lower than in the first wave and was similar to the second wave . The CFP for males and females was similar between these three waves .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms. LRT samples are also best for attempting isolation of infectious virus, although the success of culture is reduced when disease persists . Recommended sample types include bronchoalveolar lavage , tracheal/tracheobronchial aspirate, pleural fluid and sputum . Fresh samples yield better diagnostic results than refrigerated material and if delays in testing of \u226572 h are likely, samples should be frozen at \u221270\u00b0C . If available, lung biopsy or autopsy tissues can also be tested . Title: Risk of tuberculosis among air passengers estimated by interferon gamma release assay: survey of contact investigations, Japan, 2012 to 2015", "Passage: flight duration of 8 hours or longer stipulated in the WHO guideline. Title: Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda\nPassage: For monitoring of the measles program, serum specimens from patients with suspected measles are collected and transported from the health facilities to the NRL. The samples are analyzed for viral antibodies by ELISA. The results are given to EPI for their use in determining a timely response. The results are shared with WHO-AFRO on a monthly basis. Serum specimens also are sent to UVRI on a quarterly basis for external quality control. In addition, the NRL receives quality control panels every quarter from UVRI. Title: Results From the First Six Years of National Sentinel Surveillance for Influenza in Kenya, July 2007\u2013June 2013", "Passage: and non-fatal cases. Multivariable logistic regression and GLM models were constructed using factors that were significant at p,0.2 in the bi-variate analysis. SARI patients ,5 years old and those $5 years old were analyzed separately because different case definitions were used for the two age groups. Findings were considered statistically significant if the p-value was ,0.05. Data analyses were performed using Stata 12.1 .", "Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919\nPassage: The second wave of the 1918 pandemic differed from the first in that much higher morbidity and mortality rates were reported, with the majority of all fatalities associated with the pandemic occurring during this wave . Ultimately, the pandemic would result in an estimated 500 million infections worldwide and a case fatality rate > 2.5%, more than 25 times higher than any other pandemic . As a testament to the severity of this second wave, during the fall of 1918, the first 4-5 pages of Spanish newspapers were filled with obituaries of those who had succumbed to the pandemic virus Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: The 1918-1920 influenza pandemic, or the so-called Spanish flu, was responsible for more than 50 million deaths worldwide . In Europe, the excess mortality rate associated with the 1918-1919 influenza pandemic has been estimated at 1.1%, or approximately an 86% increase in all-cause mortality . This pandemic rapidly spread in a series of pandemic waves that gripped the world beginning in early 1918 . However, according to results of various phylogenetic and molecularclock analyses, the initial circulation of the virus from avian or swine and other mammal species to humans may have occurred a few years earlier . Moreover, the Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: Although mortality rates were low, the pandemic would ultimately claim between 500,000 and 2 million lives . In April 2009, the 2009-2010 swine flu pandemic, subtype H1N1, began with nearly simultaneous outbreaks in Mexico and the US, before spreading globally over the next 6 weeks. While the 2009-2010 pandemic had a low associated case fatality rate, resulting in 284,000 deaths worldwide, it had devastating effects on global economies and healthcare networks . Conventionally, influenza pandemics result in the extinction of previously circulating virus strains; however, this view was complicated by events in 1977. Although H1N1 was replaced by H2N2 as Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Total excess mortality for epidemic weeks during the observed period was highest during the second fall-winter wave in 1918/ 1919. We found a total excess rate of approximately 33.5 deaths per 10,000 persons, based on all-cause deaths and 22.3 per 10,000 based on respiratory-related deaths. In contrast, the spring-summer wave was associated with an excess death rate at 8.2 per 10,000 persons, based on respiratory-related deaths and 19 per 10,000 for all-cause deaths. It is interesting that the third wave in winter of 1919-1920 generated a substantial death rate at 34 deaths per 10,000 persons, based on all-cause deaths, which", "Title: The Impact of Contact Tracing in Clustered Populations\nPassage: The results of Figure 2 were obtained by fitting the improved pairwise model to a given endemic state, I \u00c3~0 :5. The impact of this fitting on the transmission rate and number of \u00bdI{I pairs, while varying the clustering coefficient w, is shown in Figure 2 , panes C and D. Title: The Impact of Contact Tracing in Clustered Populations\nPassage: be the subject of case by case investigation. Title: The Impact of Contact Tracing in Clustered Populations\nPassage: Here, \u00bdA{B/C is the number of nodes of type B connected to both an A and a C, which may or may not be connected themselves. Title: Mapping road network communities for guiding disease surveillance and control strategies\nPassage: one community. The four maps shown are example outputs, but any number of communities can be identified. The clustering that maximises modularity produces 104 communities, and these are mapped in Fig. 4 .", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: There are several approaches to avoiding pre-existing vector immunity, such as the use of vectors derived from nonhuman sources, using human viruses of rare serotypes , heterologous prime-boost approaches , homologous reimmunization and removing key neutralizing epitopes on the surface of viral capsid proteins . The inhibitory effect of pre-existing immunity can also be avoided by masking the Ad vector inside dendritic cells . In addition, mucosal vaccination or administration of higher vaccine doses can overcome pre-existing immunity problems . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Other studies have evaluated cellular responses. A study by Sevil Dom\u00e8nech and colleagues reported that pre-existing anti-vector immunity seriously compromises CD8 + responses in mice when exposed to a similar strain used as vector . In contrast, another study by the same authors reported that animals exposed to related vectors induce much higher CD8 + responses when compared with animals which do not have any pre-existing Salmonella immunity . The difference between these two studies was that in the first, the prime and boost were with identical serovars, while in the second study, different serovars were used. This may point Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: As some of the vectors in use will have been seen by the host immune system prior to vaccination, whether the presence of pre-existing immune responses is detrimental for the further development of a vector-based vaccine scheme, or can augment responses to the vectored antigen, needs to be considered in detail. This is the subject of this review. In discussing the possible effects on pre-existing immunity, the natural immunity to the vector needs to be considered. Therefore, considering a vector such as Salmonella, if a host has previously been infected there will exist robust B and T memory responses, and", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Since this study, a host of peer-reviewed reports have looked at both DCs and other animals, and the possibility that they may host MERS-CoV infection. Seropositive DCs have been found throughout the Arabian Peninsula including Oman, the KSA, Qatar, Jordan, the United Arab Emirates , Kuwait as well as Sudan, Somalia, Egypt, Tunisia, Nigeria, Kenya and Ethiopia in Africa and the Canary Islands . Other animals tested include sheep, cows, pigs, horses, donkeys, mules, birds, water buffalo, goats, Bactrian camels, llamas and guanaco but none had detectable neutralising antibody against MERS-CoV . No virology or serology studies of human samples Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Since that first report, a slow discovery process over the following two to three years revealed a virus that had infected over 90 % of adult dromedary camels in the KSA , also DCs across the Arabian Peninsula and parts of Africa that are a source of DC imports for the KSA . To date, MERS-CoV has not been detected in DCs tested in zoos or herds from other parts of the world . Occasionally, virus is transmitted from infected DCs to exposed humans. Subsequent transmission to other humans requires relatively close and prolonged exposure .", "Title: Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies\nPassage: antigenic drift, serological surveillance of avian samples is also particularly important . Serological techniques play a key role in various aspects of influenza surveillance, vaccine development, and evaluation and they can be used to assess the presence of antibodies to past infections and responses to a circulating influenza strain or vaccine components . From a veterinary point of view, serological and virological surveillances are necessary not only as monitoring systems for AI viruses circulating among poultry species but also as a prevention and control tool for those strains with possible pandemic potential . Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Serological testing such as ELISA, IIFT and neutralization tests are effective in determining the extent of infection, including estimating asymptomatic and attack rate. Compared to the detection of viral genome through molecular methods, serological testing detects antibodies and antigens. There would be a lag period as antibodies specifically targeting the virus would normally appear between 14 and 28 days after the illness onset . Furthermore, studies suggest that low antibody titers in the second week or delayed antibody production could be associated with mortality with a high viral load. Hence, serological diagnoses are likely used when nucleic amplification tests are Title: Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies", "Passage: insufficient for predicting which influenza strains will mutate into HPAI variants . Despite significant efforts being put into the development of avian vaccines, serological surveillance represents one of the major tools for evaluating the immune state of avian populations especially for the ability of certain subtypes 2 Journal of Immunology Research to mutate due to their longterm circulation among vaccinated populations . Serology represents a powerful and sensitive approach for detecting the presence of avian influenza antibodies in a population but the occurrence of antigenic drift and shift must be taken into consideration as it can render subtype-specific serologic tests Title: Viral factors in influenza pandemic risk assessment", "Passage: Pandemic threat assessment can also be enhanced by immunological surveys of human populations in geographical area where strains of concern are known to be circulating . Serological surveys can help to estimate the frequency of spillover infections from non-human to human hosts and also to assess the degree of cross reactivity arising from endemic human strains that share recent genomic ancestors with non-human strains of concern . Attempts have been made to use serological surveys to estimate the rate of spillover infections to humans for recent strains of concern Van Kerkhove et al., 2012) . Sometimes blood samples are obtained", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: characterization . As more genomes from both humans and DCs have been characterized, two clades have become apparent; A and B . Clade A contains only human-derived MERS-CoV genomes from Jordan, while Clade B comprises the majority of human and camel genomes deduced thus far . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: DC samples were confirmed by sequencing a 358 nt portion of the spike gene; these sequences were identical to each other, again with close homology to other human and DC MERS-CoV sequences . The DCs and human contacts yielded ORF1a and ORF4b sequences differing by only a single nucleotide each, clustering closely with the Hafr-Al-Batin_1_2013 variant . Subsequent case studies found evidence of a concurrent human and DC infection and the direction of that infection was inferred to be from the ill DCs and to their human owners . Partial genome sequences indicated that a human and a MERS-CoV RT-rtPCR Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Genome sequence located to a distinct clade were identified from an Egyptian DC that was probably imported from Sudan. This does not fit into either of the current clades . A virus sequenced from a Neoromicia capensis bat was more closely related to MERS-CoV than other large bat-derived sequences had been to that point, but the genome of a variant of a MERS-CoV has yet to be discovered and deduced from any bat .", "Title: Oligomerization domains in the glycan\u2010binding receptors DC\u2010SIGN and DC\u2010SIGNR: Sequence variation and stability differences\nPassage: DC-SIGN and its homologs are subject to rapid genetic change. 18 The 23-amino acid repeat units of the neck domain are present only in primates. A very divergent set of eight homologous genes is found in mice. 19 Based on the roles of some of the key amino acids in the neck domain described here, comparison of the DC-SIGN and DC-SIGNR genes in the primates provides some insights into the potential functional effects of these genetic variations . Some of the distinct structural features conserved in the DC-SIGNR genes are the presence of the stabilizing leucine residue at position 6 Title: Biological Activities of Secretory RNases: Focus on Their Oligomerization to Design Antitumor Drugs", "Passage: and to undergo a reciprocal exchange of a protomer domain with the equivalent domain of an adjacent subunit. Therefore, a non-covalent dimer, or even larger oligomers, if more than a single flexible loop is present, can be formed . The domain detached from the native monomer can reconstitute the native protomer contacts in each composite, functional unit of the oligomer . The novel FU overlaps the native monomer, except for an additional interface, whose conformation depend to each particular protein, and that is/are absent in the native monomer . The domains involved in 3D-DS are often the protein N-or C-termini, Title: Oligomerization domains in the glycan\u2010binding receptors DC\u2010SIGN and DC\u2010SIGNR: Sequence variation and stability differences", "Passage: In addition to differences in stability reflecting minor variations in the sequences of the repeat units in the neck domains of DC-SIGN and DC-SIGNR, differences in the properties of the neck domains could arise from differences in the number of repeat units in polymorphic forms of DC-SIGNR. To compare these factors, multiple versions of the neck domain were created with 3 to 7.5 copies of the 23amino acid repeat unit containing leucine at position 6 and arginine at position 15. Title: Deep Sequencing Analysis Reveals the Mycoviral Diversity of the Virome of an Avirulent Isolate of Rhizoctonia solani AG-2-2 IV", "Passage: on the assembled virome data, it was possible to identify 17 contigs encoding different viral RdRp domains. For detailed analysis, these RdRp domains were re-sequenced based on whole RNA extracts and partial domains were completed. These data were used for taxonomic classification. The identified RdRps belong to four different protein families corresponding to either the alphavirus-like superfamily, the picornavirus-like super family or the Narnaviridae. They showed similarities from 31 to 93% to RdRp domains of viral sequences deposited in the NCBI database.", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: Text: On 29 December 2019 clinicians in a hospital in Wuhan City, China noticed a clustering of cases of unusual pneumonia with an apparent link to a market that sells live fish, poultry and animals to the public. This event was reported to the World Health Organisation on 31 December . Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: We were also aware that the clinical studies we analysed differed with respect to which comorbidities or identifiable causes for exacerbations were reported. Most patients were elderly and therefore were more likely to be suffering from one or more co-existing diseases such as asthma or cardiovascular disease. Such co-morbidity makes interpretation of our findings more difficult with respect to the true causes of exacerbations. If their aetiology could be determined, then susceptible patients such as those in Level I could be identified and new treatments developed to help prevent their onset and related hospital costs. Title: Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children", "Passage: xacerbations are the primary cause of morbidity and mortality in children with asthma and occur despite current treatments. It has been established that the majority of exacerbations are provoked by viral respiratory infections, most notably rhinoviruses ; however, exacerbations also occur in the absence of infections 1,2 . Furthermore, even in children with severe asthma, the majority of respiratory infections do not progress to exacerbation 3 . The fundamental question of why some but not all colds lead to exacerbations has not been fully answered, and the similarities and differences between the mechanism of virus-associated and nonviral exacerbations are unknown. Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Chronic obstructive pulmonary disease is a respiratory disease characterized by an airflow limitation and inflammation of the lower airways . As the disease worsens, some patients experience 'exacerbations' of their principal symptoms of dyspnoea, cough and sputum. These exacerbations frequently result in a visit to a general practitioner's office or to a local hospital for treatment. Exacerbations occur in COPD patients at a median of three times a year with half of them being unreported . The heterogeneity of COPD exacerbations make them difficult to define, classify and manage due to their range of symptoms, varied treatment requirements, seasonal occurrence,", "Title: DGV: Dengue Genographic Viewer\nPassage: Asian I was predominant in Thailand, whereas genotype Asian American was predominant in Cambodia and Vietnam . From 2001, Asian I increased in Cambodia and Vietnam until finally in 2007 Asian I became the predominant genotype in Indochina. The genotype Asian I viruses in Thailand seemed to be widely disseminated into Vietnam via Cambodia but did not reach Malaysia and Bangladesh . Thus, the Asian American genotype was replaced by Asian I in Cambodia and Vietnam between 1998 and 2011. This example also suggests the idea of genotype transition, which probably reflects the mosquito vector habitat and human activities in Title: Development and Applications of VSV Vectors Based on Cell Tropism", "Passage: This work was supported in part by grants-in-aid from the Ministry of Health, Labour and Welfare; the Ministry of Education, Culture, Sports, Science, and Technology; the 21st Century Center of Excellence Program of Japan; the Global Center of Excellence Program; and the Foundation for Biomedical Research and Innovation, Japan. Title: DGV: Dengue Genographic Viewer\nPassage: the Indochinese Peninsula. Title: A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice\nPassage: more suspected, indicating spread to continental America is possible. CHIKV is transmitted to humans by Aedes aegypti and Aedes albopictus mosquitoes, the latter of which has been an important vector in many of the recent outbreaks due to mutations in the envelope genes of the virus that allow for more efficient transmission .", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Yunnan strains such as the WIV1 had no such deletions and can use human ACE2 as a cellular entry receptor. It is interesting to note that the two bat SARS-related coronavirus ZXC21 and ZC45, being closest to 2019-nCoV, can infect suckling rats and cause inflammation in the brain tissue, and pathological changes in lung & intestine. However, these two viruses could not be isolated in Vero E6 cells and were not investigated further. The two retained deletion sites in the Spike genes of ZXC21 and ZC45 may lessen their likelihood of jumping species barriers imposed by receptor specificity. Title: Genetic diversity of the 2013\u201314 human isolates of influenza H7N9 in China", "Passage: Nonetheless, the pathogenic implications of these aminoacid substitutions, if any, are presently unknown and would require further investigation. Title: First genome report and analysis of chicken H7N9 influenza viruses with poly-basic amino acids insertion in the hemagglutinin cleavage site", "Passage: would increase the risk of AIV spreading to humans and other animals 10 . In such conditions, annual systematic and Phylogenetic analysis indicates that genes of the two novel AIVs and those of 5 human strains all were reassortant viruses . The avian strains harbored two surface glycoprotein genes from PRD clades while the other six internal genes were from the YRD clade . Different from chicken strains, the human strains in Guangdong province during the fifth wave carried two different genotypes; QY/ GIRD1 and GD/17SF006, which contained genes from three clades . GD/SP440, GD/HP001 and GD/17SF003 contained genes from Title: Genetic Analysis of West Nile Virus Isolates from an Outbreak in Idaho, United States, 2006\u20132007", "Passage: no significant difference when compared to isolates without deletions , which suggests that insertions and deletions in this variable region do not play a significant role in sfRNA formation. However, the relevance and role of the identified motifs and associated genome lesions in viral replication and their evolutionary consequences remain to be explored. The relatively high rate of occurrence of mutations, deletions and insertions in the variable region of the 3\u2032UTR suggests that positive Darwinian selection may have acted on this part of the WNV genome .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: the phage filament Hess et al., 2012) , this pioneering FIGURE 3 | Chemically addressable groups of the filamentous bacteriophage major coat protein lattice. The filamentous phage virion is made up of \u223c2,500-4,000 overlapping copies of the 50-residue major coat protein, pVIII, arranged in a shingle-type lattice. Each monomer has an array of chemically addressable groups available for bioorthogonal conjugation, including two primary amine groups , three carboxyl groups and two hydroxyl groups . The 12 N-terminal residues generally exposed to the immune system for antibody binding are in bold underline. Figure adapted from structural data of Marvin, 1990 , Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: the phage filament Hess et al., 2012) , this pioneering FIGURE 3 | Chemically addressable groups of the filamentous bacteriophage major coat protein lattice. The filamentous phage virion is made up of \u223c2,500-4,000 overlapping copies of the 50-residue major coat protein, pVIII, arranged in a shingle-type lattice. Each monomer has an array of chemically addressable groups available for bioorthogonal conjugation, including two primary amine groups , three carboxyl groups and two hydroxyl groups . The 12 N-terminal residues generally exposed to the immune system for antibody binding are in bold underline. Figure adapted from structural data of Marvin, 1990 , Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: The filamentous phage particle is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups . The regularity of the phage pVIII lattice and its diversity of chemically addressable groups make it an ideal scaffold for bioconjugation . The most commonly used approach is functionalization of amine groups with NHS esters , although this can result in unwanted acylation of pIII and any displayed biomolecules. Carboxyl Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: The filamentous phage particle is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups . The regularity of the phage pVIII lattice and its diversity of chemically addressable groups make it an ideal scaffold for bioconjugation . The most commonly used approach is functionalization of amine groups with NHS esters , although this can result in unwanted acylation of pIII and any displayed biomolecules. Carboxyl", "Title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia\nPassage: Text: Neonatal calf septicemia causes high morbidity and mortality and is one of the leading and most significant difficulties in raising cattle. Calf septicemia is the main cause of death in the neonatal period . Its etiology involves bacteria , viruses , parasites, and other factors. As the disease progresses quickly and is lethal, diagnosis and treatment should be initiated as quickly as possible . Title: Bacteriological study of calf colisepticemia in Alage Dairy Farm, Southern Ethiopia", "Passage: Neonatal calf diarrhea is the principal cause of calf mortality affecting the livestock industry globally . Septicemia caused by E. coli is a common disease of neonatal calves which causes a severe diarrhea and mortalities. The disease has a complex pathology which is known to have a multiple etiological agent . Some of the pathogenic organisms which causes calf diarrhea includes bacteria, viruses, and protozoa . Co-infection make control of the disease more complicated . Many reports showed that E. coli is one of the cause of enteropathogenesis in early ages of calves . The incidence of calf diarrhea in Title: Bacteriological study of calf colisepticemia in Alage Dairy Farm, Southern Ethiopia", "Passage: neonates is reported in several studies and revealed a prevalence of 15-20% and rate of mortality showed from 1.5 to 8% . In addition, the frequent presence of non-specific clinical signs ae the main factors influencing targeted treatments . Diagnostic methods such as ELISA and PCR showed a better degree of detecting during mixed infections and strain based diagnosis is important in providing appropriate information for proper therapeutic applications and finally control of the disease . Various studies showed that different bacterial infections specifically the enterotoxigenic, enteropathogenic, enteroinvasive, and enterohemorrhagic E. coli leads to calf colisepticemia and causes neonatal mortalities Title: Bacteriological study of calf colisepticemia in Alage Dairy Farm, Southern Ethiopia", "Passage: by Ghanbarpour and Mohammad revealed a prevalence of 22% and it is comparably higher than the prevalence of the present study. This is due to the age of the neonates which was less than 10 days and all were clinically ill with calf diarrhea. This is justifiable because neonates are more susceptible to infection comparing to the older calves.", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: DNA methylation signatures in peripheral blood strongly predict all-cause mortality\nPassage: 1. I found the study design slightly confusing. Why did the authors' not include covariates in the discovery panel but did in the replication analyses? A flow chart figure of the study design would be helpful. Title: Temporal trends in the discovery of human viruses\nPassage: is therefore of considerable interest. Title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study\nPassage: studies with larger sample sizes should be conducted to verify our preliminary results.", "Title: Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4(+) CD25(+) Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice\nPassage: Previous microarray analyses showed that expression of mRNA coding for the fibrinogenlike protein 2 were significantly up-regulated in the liver of mice perorally infected with E. multilocularis eggs . FGL2, a member of the fibrinogen-related superfamily of proteins secreted by T cells, has recently been reported by a number of groups to be highly expressed in Tregs. Its role was associated to Treg effector functions . It was shown that FGL2 could inhibit dendritic cell maturation through binding to the low-affinity FcgammaRIIB receptor, and thus contribute to Treg activity . There is evidence that FGL2 exerts an immunosuppressive effect on Title: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events", "Passage: Specifically, the glycoprotein fibrinogen is a multimeric protein and consists of \u03b1, \u00df and y subunits. It is synthesized by hepatocytes and an essential blood coagulation factor with all polypeptide chains being highly regulated in tumours of EGF transgenic mice. Note, an association between coagulation factors and malignancies was established whereby fibrinogen functions as an extracellular matrix protein to interact with integrin receptors in the control of cell proliferation and cell migration . Accordingly, induced gene expression of the integrin receptors Itgb1, Itga3 and Itgav was observed in EGF induced liver tumours. In cancer progression a regulatory loop between fibrinogen, Title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression", "Passage: Prothrombinase Fgl2 belongs to the fibrinogen superfamily and is produced by activated macrophages or endothelial cells, transforming prothrombin directly into thrombin, so as to quickly initiate the process of coagulation. This promotes the conversion of fibrinogen into fibrin, resulting in thrombosis . Our study found that Fgl2 was highly expressed in peripheral blood mononuclear cells and in liver tissue of humans or mice with severe viral hepatitis, and was positively related to the severity of the disease . Gene therapy targeting Fgl2 silencing showed that the survival rate of fulminant hepatitis mice increased from 0 to 33.3% . Thus far, Title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression", "Passage: Prothrombinase Fgl2 belongs to the fibrinogen superfamily and is produced by activated macrophages or endothelial cells, transforming prothrombin directly into thrombin, so as to quickly initiate the process of coagulation. This promotes the conversion of fibrinogen into fibrin, resulting in thrombosis . Our study found that Fgl2 was highly expressed in peripheral blood mononuclear cells and in liver tissue of humans or mice with severe viral hepatitis, and was positively related to the severity of the disease . Gene therapy targeting Fgl2 silencing showed that the survival rate of fulminant hepatitis mice increased from 0 to 33.3% . Thus far,", "Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses\nPassage: Generating an effective immune response is not only fundamental for therapeutic antibody discovery, but is also crucial for vaccine development in combating infectious disease. Both begin with the host immune response elicited against the foreign antigen/vaccine after immunization. While animal immunization for therapeutic antibody generation requires a mechanism-driven strategy for obtaining antibodies that can demonstrate the therapeutic mode of action prior to hybridoma fusion and/or B-cell recovery efforts, vaccine development emphasizes the stimulation of protective immune responses by the host's immune system that are of sufficient strength and quality to sustain efficient and long term protection . The development of Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses", "Passage: also be applied to advance vaccine development toward the goal of developing robust vaccines. Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses\nPassage: an optimal immune response to meet either goal is challenging due to the sophisticated mechanisms that control immune responses . The process often involves multiple critical considerations, such as the selection of candidate antigens, choice of adjuvant, antigen/ vaccine design, dosage, frequency of application, duration of immunization, injection protocols, etc. . Immune responses are typically monitored by measuring antibody titers in the blood samples collected from the immunized hosts over the course of immunization. While many commercial kits and automated systems are available, ELISA remains the most widely used method for antibody titer measurements due to its simplicity and low Title: Virus-Vectored Influenza Virus Vaccines", "Passage: induction of humoral responses to the hemagglutinin protein, the major surface and attachment glycoprotein on influenza. Serum antibody responses to HA are measured by the hemagglutination-inhibition assay, and the strain-specific HI titer is considered the gold-standard correlate of immunity to influenza where a four-fold increase in titer post-vaccination, or a HI titer of \u22651:40 is considered protective . Protection against clinical disease is mainly conferred by serum antibodies; however, mucosal IgA antibodies also may contribute to resistance against infection. Split virus inactivated vaccines can induce neuraminidase -specific antibody responses , and anti-NA antibodies have been associated with protection from infection", "Title: Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus\nPassage: recently emerged Indian Ocean lineage . CHIKV is composed of a positive, single-stranded genomic RNA of 12 kilobases, encoding four non-structural and five structural proteins . The non-structural proteins, nsP1, nsP2, nsP3 and nsP4, are required for virus replication . A sub-genomic RNA encodes the structural proteins: capsid , E3, E2, 6k and E1, and thus a polyprotein is produced which is then processed by the capsid auto-proteinase and signalases . The CHIKV surface is mainly composed by E1-E2 heterodimers where E1 glycoproteins mediate fusion and E2 glycoproteins interact with the host receptor . Since its discovery the virus has Title: Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus", "Passage: was named sCHIKV \u2206C. Forward primer: ATGGAGGAATGGTCCCTGGCTATC. Reverse primer: TCATCAGTGCCGGCTGAAG. Title: A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice\nPassage: CHIKV causes a dengue-like illness associated with fever, rash and joint pain and was first described in modern day Tanzania in 1952 . The term Chikungunya is derived from the Makonde word meaning ''that which bends up'' and describes the posture of an infected individual . Recently, the U.S. Army developed a live-attenuated vaccine candidate, called CHIK 181/clone 25 or 181/25, but it caused transient arthralgia in a small number of volunteers during phase II clinical trials . Experimental subunit , recombinant viruses , and VLP based vaccines have also been described which are currently at various stages of preclinical Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: CHIKV mosquito-borne disease has caused massive outbreaks for at least half a century but is no longer confined to the www.plosntds.org developing nations. It began to encroach into the boundaries of the developing world. As a result, the NIAID has designated CHIKV as a Category C pathogen alongside the influenza and SARS-CoV viruses . Realization of the potential severity of this disease is exigent; for instance, if used as a biological weapon, the world economy could be severely crippled; if enough members of the armed forces were to become infected during a military deployment, military operations could be significantly affected.", "Title: Detection of a Fourth Orbivirus Non-Structural Protein\nPassage: The RNA of BTV-8 or GIV was separated by 1% agarose gel electrophoresis. Seg-9 was cut from the gel using a clean scalpel blade, purified using RNaid kit and cDNA was synthesised using a single primer amplification technique as previously described ). The ORFs in Seg-9 from BTV-8 and GIV were PCR amplified using specific primers tailed with restriction enzyme sites shown in table 1. Title: Identification of Nuclear Localization Signals in the ORF2 Protein of Porcine Circovirus Type 3\nPassage: GraphPad Prism software was used for data analysis. Data from three independent experiments were shown as the mean \u00b1 standard error . The differences between groups were determined by one-way ANOVA. Title: Analysis of codon usage and nucleotide composition bias in polioviruses", "Passage: 48 available representative complete ORFs of poliovirus to obtain some clues to the features of genetic evolution of the virus. Title: Structural Proteomics of Herpesviruses\nPassage: Nevertheless, proteogenomics is more often regarded as a way to refine ORF prediction, which is by definition imperfect and sometimes misses coding sequences or inaccurately defines gene boundaries. In particular, small ORFs are probably too often rejected by traditional ORF prediction tools . Thus, proteomic data can be searched against a database construct using translation of all six reading frames of genomic data. Alternatively, a database can be constructed as a stop-to-stop list of ORF that is eventually limited in size. Using such a strategy, a study by Varnum et al. highlighted six new short ORFs that were not predicted", "Title: Neonatal Pertussis, an Under-Recognized Health Burden and Rationale for Maternal Immunization: A Systematic Review of South and South-East Asian Countries\nPassage: The most common symptoms a pertussis patient presents are cough with or without paroxysms, cyanosis, apnea, tachypnea, difficulty in breathing and leukocytosis. In a study from the Philippines, pertussis patients presented with paroxysms of cough , accompanied by cyanosis and tachypnea . The characteristic whoop was not seen in any of the Among which number of ICU admissions: a = 3 ICU intensive care unit, nr not reported patients. All patients had leukocytosis , lymphocytic predominance and thrombocytosis . In another study from Nepal, the most common symptoms were cough and difficulty in breathing . Similar symptoms were noted in Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: Although cough, difficulty breathing, and cough with vomit were the most common symptoms, no symptom was present in all B pertussis cases. During an epidemic period in Washington state, among infants <1 year, who had a minimum of 14 days cough plus an additional symptom, 82% had posttussive emesis, 29% had apnea, 26% had whoop, and 42% had cyanosis . A study of US neonates with pertussis showed the symptom prevalence to be 97% for cough, 91% for cyanosis, 58% for apnea, and 3% for fever . Our study found lower or equal symptom prevalence with the exception of fever. Title: Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness", "Passage: On admittance, 93% of infants were coughing, and 73% also suffered from coughing attacks . Other classical pertussis symptoms such as prolonged inspiratory effort, whooping, vomiting, and apneas were reported in up to 35% of infants. Reported symptoms at admission did not differ between terms and preterms, except that cyanosis more often occurred in terms . Title: Vaccination against Paediatric Respiratory Pathogens\nPassage: The classic manifestation of the disease can be divided into three phases: nonspecific symptoms, such as coryza, fever, and occasional cough; constant and uncontrollable cough after two weeks, followed by forced inspiration producing a whooping sound; and the convalescence phase, in which symptoms decrease progressively, and complications can appear. Complications, such as pneumonia, are frequent and are responsible for over 90% of the deaths attributable to the disease in children younger than one year of age .", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: Assessing health-evidence.ca user and visitor areas of interest Registered user areas of interest were assessed by querying the health-evidence.ca registered user database and looking at the areas of interest identified by all users who registered up to December 31, 2010. Data were aggregated by topic area. Registered user data is provided voluntarily by users and aggregation ensures individual data remain anonymous. Topic areas of interest were ranked from highest to lowest rates of user interest. The top 10 areas of interest were summed to generate the denominator: total user interest in the top 10 topic areas. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: Visitor areas of interest were assessed by summing frequency of visitor searches of the 21 Focus of Review topic areas and visitor use of the topic area browse menu for the period January 1, 2010 to December 31, 2010. Visitor site usage is tracked via Google Analytics, a web analytics tool that collects and aggregates nonpersonal data to report on visitor interaction with the health-evidence.ca website. Total search and browse access by unique visitors were ranked from highest to lowest pageviews. The top 10 areas of interest were summed to generate the denominator: total visitor interest in the top 10 Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: Topic areas with a large quantity of systematic reviews include: mental health , physical activity , addiction/substance use , adolescent health , child health , nutrition , adult health , and chronic diseases . All of the topic areas with many available reviews were of interest to registered users and/or visitors. Chronic diseases, nutrition, and, physical activity were the three highest-ranking areas of interest common across both groups. The number one visitor area of interest and number two registered user area of interest was chronic diseases with 3, 115 visitor searches submitted in 2010, and 2, 153 registered users expressing Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: The top 10 topic areas of interest of registered users and the top 10 topic areas of interest of visitors of http:// www.health-evidence.ca, as well as the availability of review evidence by methodological quality, are identified in Table 1 . The top areas of interest and the total number of reviews available included: addiction/substance use , adolescent health , adult health , child health , chronic diseases , communicable disease/infection , healthy communities , injury prevention/safety , mental health , nutrition , parenting , physical activity , reproductive health , and social determinants of health .", "Title: Detection of Common Respiratory Viruses and Mycoplasma pneumoniae in Patient-Occupied Rooms in Pediatric Wards\nPassage: Viral infections of the respiratory system are very common. In Taiwan, the predominant viruses isolated from patients with respiratory infections are enterovirus, respiratory syncytial virus , influenza A and B viruses, adenovirus, cytomegalovirus, herpes simplex virus-1, and parainfluenza virus. 27 Enterovirus causes herpangina, hand-foot-and-mouth disease, myocarditis, encephalitis, and death. RSV is the most common pathogen of the lower respiratory tract in infants 28 and a common cause of nosocomial infections in pediatric wards. 29 Influenza A and B viruses cause seasonal epidemics in Taiwan, especially in winter. 30 Adenovirus causes acute respiratory tract infections in children younger than 5 years Title: Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection", "Passage: Acute respiratory viral infections are among the most common reasons for patient visits in primary and acute care settings . Many viruses cause such acute respiratory illness including human rhinovirus , respiratory syncytial virus and influenza. These viruses can be associated with a range of clinical severity from asymptomatic to mild, self-limited illness to respiratory failure and death. Influenza alone causes 25 to 50 million infections annually in the USA, resulting in several hundred thousand hospitalizations and 20-40,000 deaths . Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: Rhinoviruses are responsible for more than one-half of upper respiratory tract infections and they are considered to be among the most frequent infectious agents in humans worldwide . Most cases of RV infections are benign, self-limited cold-like illnesses. However, these viruses have been also identified as the causal agent of severe pneumonia in the elderly and immunocompromised patients, as well as exacerbations of chronic obstructive pulmonary disease and asthma. At present, no efficient antiviral treatment, vaccines, or other preventive measures exist against these particularly frequent pathogens . In addition to the significant associated clinical morbidities, the economic impact of RV-related Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: Baculovirus has been extensively used to produce recombinant proteins. Recently, a baculovirus-derived recombinant HA vaccine was approved for human use and was first available for use in the United States for the 2013-2014 influenza season . Baculoviruses have also been explored as vaccine vectors. Baculoviruses have a number of advantages as vaccine vectors. The viruses have been extensively studied for protein expression and for pesticide use and so are readily manipulated. The vectors can accommodate large gene insertions, show limited cytopathic effect in mammalian cells, and have been shown to infect and express genes of interest in a spectrum of Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus", "Passage: cells and larvae could reach a tenfold difference. When we use the same amount but different quality of reBmBac DNA to mix with the same tube of well-preserved pVL1393-luc vector and to carry out the cotransfection, the luminescence from cells and larvae were at least fivefold different. Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus", "Passage: Baculoviruses are a group of large viruses with circular double-stranded DNA genomes of 88-153 kb , which makes it laborious to manipulate and generate recombinant baculoviruses. Therefore, several construction strategies have been developed to increase the efficiency of recombinant baculovirus generation. To generate the recombinant AcMNPV, Patel et al. have developed a recombinant baculovirus shuttle strategy in yeast with yeast Vector and E. coli TransforMax EPI300 were obtained from Epicentre . DH10Bac/pMON7124 , transfer vector pVL1393 and Lipofectin were obtained from Invitrogen. Low-melting agarose was obtained from Sigma-Aldrich . Anti-PoIFN-\u03b3 antibody was obtained from Millipore , and goat anti rabbit Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines", "Passage: Theoretically, baculovirus-expressed VLP vaccines provide an excellent alternative over inactivated vaccines. However, baculovirus-expressed VLPs have rather low yields, a major issue that impedes their utilization for mass production in real life. Such low yields would translate to being economically non-feasible for large-scale production . There are many efforts in trying to improve the yields of baculovirus-expressed VLPs, such as placing both 3CD and P1 into one recombinant vector, as well as using different promoters for 3CD and P1 to obtain an optimal 3CD:P1 protein ratio . In addition, a research group has recently employed the use of suspension Hi Five", "Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome\nPassage: channel activity-loss mutant, 3a-CS . To test whether the ion channel activity of the SARS-CoV 3a protein is required to stimulate secretion of IL-1\u03b2, we transduced LPSprimed BMMs with lentiviruses expressing the SARS-CoV E, V25F, 3a, 3a-CS, or M proteins. Consistent with a previous report , we found that the V25F mutant lentivirus failed to stimulate IL-1\u03b2 release from BMMs . Notably, the 3a-CS mutant completely abrogated IL-1\u03b2 secretion , suggesting that the ion channel activity of the 3a protein is required for SARS-CoV 3a-induced IL-1\u03b2 secretion. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: In summary, we found that the ion channel activity of SARS-CoV 3a protein is essential for activation of the NLRP3 inflammasome. In addition, both K + efflux and mitochondrial ROS production are required for SARS-CoV 3a-mediated IL-1\u03b2 secretion. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Finally, we investigated the mechanism by which SARS-CoV 3a triggers NLRP3 inflammasome activation. A previous study showed that the 3a protein of SARS-CoV acts as a K + channel . In addition, K + efflux is a well-known activator of the NLRP3 inflammasome . These observations prompted us to examine whether K + efflux is required for 3a-mediated IL-1\u03b2 secretion. To this end, BMMs in K + -rich medium were infected with influenza A virus or lentiviruses expressing the SARS-CoV E or 3a proteins. In agreement with a previous result , we found that IL-1\u03b2 secretion caused by influenza virus Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Previous studies demonstrated that the N-terminal 40 amino acids of the SARS-CoV E protein are important for ion channel formation, and that mutations N15A and V25F ] prevent ion conductivity . In addition, the SARS-CoV 3a protein contains a cysteine-rich domain that is involved in the formation of a homodimer to generate the ion channel . Thus, mutation of the cysteine-rich domain blocks the ion conductivity by the 3a protein . To this end, we substituted amino acids Cys-127, Cys-130, and Cys-133 within the cysteine-rich domain of the SARS-CoV 3a protein with serine to generate a lentivirus expressing the ion", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Similarly, childhood tuberculosis is a major cause of morbidity and mortality in many low-and middle-income countries, and Mycobacterium tuberculosis has increasingly been recognized as a pathogen in acute pneumonia in children living in high tuberculosis-prevalence settings. Postmortem studies of children dying from acute respiratory illness have commonly reported M. tuberculosis . A recent systematic review of tuberculosis as a comorbidity of childhood pneumonia reported culture-confirmed disease in about 8% of cases . Because intrathoracic tuberculosis disease is only culture-confirmed in a minority of cases, the true burden could be even higher; tuberculosis could therefore be an important contributor to childhood Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Childhood pneumonia can also lead to significant morbidity and chronic disease. Early life pneumonia can impair longterm lung health by decreasing lung function . Severe or recurrent pneumonia can have a worse effect on lung function; increasing evidence suggests that chronic obstructive pulmonary disease might be related to early childhood pneumonia . A meta-analysis of the risk of long-term outcomes after childhood pneumonia categorized chronic respiratory sequelae into major and minor groups . The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Childhood pneumonia and clinically severe disease result from a complex interaction of host and environmental risk factors . Because of the effectiveness of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination for prevention of radiologic and clinical pneumonia, incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases Title: Tuberculous pneumonia-induced severe ARDS complicated with DIC in a female child: a case of successful treatment", "Passage: TB continues to be one of the causes of disease and death among children worldwide, particular in developing countries with a poor public health infrastructure . While TB-associated ARDS in adult patients has been reported , surveillance data for estimating the contribution of TB to pediatric ARDS remains limited . Thus, it can be speculated that many pediatric patients with TB pneumonia induced-ARDS have not been reported in the literature. More robust data on the epidemiology of childhood TB are needed in order to determine not only the contribution to ARDS but also to develop pediatric-specific therapeutic strategies. Previous reviews", "Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1\nPassage: The results of the simulations are given in Figure 1 and 2. Consistent with our theoretical results we observe that when the reporting fraction is constant, the estimates of R0 are unaffected by a failure to control for missingness. However if the reporting fraction increases, then the estimates are smaller when we adjust for the missingness. We also note that has recently described a tendency of this method to overestimate the mean of the serial interval when the serial interval is short, such as in cases of influenza. Thus part of the effect seen could be attributed to this phenomena, Title: Estimating the number of infections and the impact of non-\nPassage: underreporting as well as systematic and country-specific changes in testing. Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1", "Passage: this could possibly overestimate the true number of cases. Further, as time has progressed in the H1N1 pandemic, it has become virtually impossible to ascertain all cases. Therefore it is likely that reporting initially increased and then began to decrease again as case counts escalated. Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: population; we would know who was infected and who was not , with high confidence. The reporting rate is the ratio of reported cases over the number of seropositive individuals. It was statistically evident that increasing in reporting was likely, and thus it should be considered in the future investigation of this outbreak.", "Title: A bibliometric analysis of IL-35 research from 2009 to 2018\nPassage: further analysis. Title: Inference and forecast of H7N9 influenza in China, 2013 to 2015\nPassage: these findings are credible. Title: Year in review 2013: critical care - respiratory infections\nPassage: trend towards better survival in the intervention arm. Title: Forecasting the 2013\u20132014 Influenza Season Using Wikipedia\nPassage: they were observed.", "Title: Viral vector-based influenza vaccines\nPassage: Next to MVA, other attenuated poxviruses have been used as viral vectors for the development of candidate influenza vaccines. Immunization of chickens with recombinant NYVAC, a VV strain highly attenuated by deletion of 18 open reading frames from the viral genome, 66 expressing the HA gene of an avian A virus ), afforded protection against infection with a heterologous A virus. 67 Recombinant Raccoonpox viruses expressing the HA, NA or NP genes of A influenza virus A/Vietnam/1203/04 were constructed and evaluated for their protective capacity in mice. Interestingly, protection from A challenge infection could be demonstrated but was dependent on Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2 . Poxviruses are also studied extensively as candidate vectors for human use, among which attenuated derivatives of vaccinia virus and New York attenuated vaccinia virus NYVAC strains] are the most promising vectors . They are ideal candidate vectors due to their large DNA-packing capacity and their thermal and genetic stability . The NYVAC vector has been shown to induce CD4 + T cell-dominant responses, and MVA induces Title: Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines", "Passage: The modified vaccinia virus Ankara is licensed in Europe and Canada as a third generation smallpox vaccine, and currently in clinical development for licensure in the United States. The relatively better safety record of MVA compared to first and second generation smallpox vaccines is well documented. This, in addition to its large capacity to accommodate heterologous genes, express encoded proteins, and elicit both humoral and cell-mediated immune responses also makes MVA an attractive vector for the delivery of several candidate vaccines for a variety of infectious and non-infectious human and veterinary diseases . Evidence for the delivery of antigens through Title: Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines", "Passage: Poxvirus vectors have also been employed as vaccine vectors with the aim of Ab induction, including in clinical trials and in a vaccinia-based licensed veterinary vaccine against rabies . For this study, we selected MVA to represent the group of replication-deficient poxviruses in development for human vaccines: MVA is among the most studied poxvirus vectors, with transgene-Ag immunogenicity favorably comparable with other poxviruses . MVA was dosed at 1 3 10 7 PFU, also at the upper end of the range of doses used in previously published mouse studies , \u223c2% of the highest dose we are aware of being", "Title: Point\u2010of\u2010care testing in primary care: A systematic review on implementation aspects addressed in test evaluations\nPassage: After removing duplicate publications from the initial search results, the abstracts were screened to determine whether publications met the inclusion criteria. Publications that undoubtedly failed to meet all of the inclusion criteria, based on the abstract screening, were excluded from the full-text assessment. If there was any doubt on whether or not a publication met the inclusion criteria, it was included for full-text assessment. The abstract screening was performed by one reviewer , and potential issues were discussed with a second reviewer when required. Title: A cell-based high-throughput approach to identify inhibitors of influenza A virus\nPassage: proving our assay was suitable for use in a high-throughput screen. Title: Point\u2010of\u2010care testing in primary care: A systematic review on implementation aspects addressed in test evaluations", "Passage: The 125 included studies consisted of 112 applied studies, 7 qualitative studies, 5 simulation studies and 1 study that used both applied and qualitative methods. The majority of the studies were applied Title: Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review\nPassage: We assessed whether methodological quality or risk of bias assessment was conducted, what tools were used, and whether the assessment was conducted in duplicate.", "Title: Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015\nPassage: Microcephaly-capillary malformation syndrome is an extremely rare disorder of the central nervous system disorder that is characterized by microcephaly, developmental delay, generalized cutaneous capillary malformation, and seizures. This syndrome has been reported in patients, both male and female, born to unrelated or consanguineous parents of various ethnicities, including Arabs. Exonic and intronic mutations in the STAM-binding protein gene are well-established causes of this syndrome in dozens of patients. This gene encodes deubiquitinating isopeptidase, which has a key role in cell surface receptor-mediated endocytosis and sorting. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: In vivo neuronal migration assessment was performed as previously described 18 using embryos at either E13 or E15 and pups at P9. Cell counts were performed using ImageJ . Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies\nPassage: In vivo neuronal migration assessment was performed as previously described 18 using embryos at either E13 or E15 and pups at P9. Cell counts were performed using ImageJ . Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: in Bardet-Biedl syndrome mouse models ciliary defects such as reduced CBF 45 and structural defects such as abnormal lengthening and swellings along their length 41 have been described, that are similar to those we describe in Katnal1 1H/1H mice. There is strong evidence that ciliopathy associated genes play a number of roles in neuronal development by affecting processes such as progenitor proliferation or maintenance of the radial glia scaffold. 43 However it is also clear that defects in microtubule organisation also affect synaptic structure. 2 At present it is difficult to disentangle the relative contributions of defects in microtubule severing", "Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: Text: Q fever is a worldwide zoonosis caused by Coxiella burnetii , a small, gram-negative obligate intracellular bacterium. C. burnetii displays antigenic variation with an infectious phase I and less infectious phase II. The primary reservoir from which human infection occurs consists of sheep, goat and cattle. Although C. burnetii infections in animals are usually asymptomatic, they may cause abortions in sheep and goats . High concentrations of C. burnetii can be found in birth products of infected mammals . Humans frequently acquire infection through inhalation of contaminated aerosols from parturient fluids, placenta or wool . Because the infectious dose Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies", "Passage: C. burnetii is a highly pleomorphic Gram-negative coccobacillus and the causative agent of Q fever. Q fever is a zoonosis, and the most common reservoirs are cattle, sheep, and goats but many other animals can be infected by C. burnetii . When infected, these domestic animals can shed the organism in urine, feces, milk, and especially birth products. The pathogen survives within the phagolysosome of host cells, and a spore stage has been described. This spore stage explains the ability of C. burnetii to survive in unfavorable environmental conditions, and it can be an environmental risk for months to years Title: Treatment of Neuroterrorism", "Passage: Q fever is caused by the intracellular coccobacillus Coxiella burnetii after exposure to infected sheep, cattle, goats, or other livestock . The bacterium's spore-like form is resistant to heat and desiccation, and it can persist for months . This form can be distributed easily by wind . It is highly infective; only 1 to 100 organisms are necessary to produce disease . It cannot be transmitted human-to-human, but tissue may pose a risk . Exposed surfaces can be decontaminated with 5% hydrogen peroxide or 70% ethyl alcohol for 30 minutes . Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: is very low and C. burnetii is able to survive in a spore-like state for months to years, outbreaks among humans have also occurred through contaminated dust carried by wind over large distances .", "Title: Using DNA metabarcoding for simultaneous inference of common vampire bat diet and population structure\nPassage: 50 ll blood was extracted and expelled onto a Whatman Flinders Technology Associates card and desiccated. Bats were kept in cloth bags until they recovered from the anaesthesia after which they were released. There were no mortality or signs of injury following bloodmeal collection. Faecal samples from individual bats were collected from cloth bags or during handling, while pooled faecal samples were collected opportunistically from underneath roosting bats and stored in RNAlater . Title: Highly diverse and antimicrobial susceptible Escherichia coli display a na\u00efve bacterial population in fruit bats from the Republic of Congo", "Passage: Bats were anesthetized in the field with Rompun 2% and Ketamin 10% . Animals were euthanized by bleeding them with cardiac puncture. Tissue samples of spleen, liver, kidney, lung and intestines were aseptically taken. Intestines were removed last to avoid contamination of organs with intestinal content. All samples were immediately preserved in liquid nitrogen and stored at -80\u02daC until further analyses. Title: ABCB1 protects bat cells from DNA damage induced by genotoxic compounds\nPassage: cells lines and genomic data/tools that enable a study of this kind. This is a valid reason for choosing these taxa and this study does represent some of the first in-depth cellular functional studies in bats but it needs to be made clear. Of the ~1300 species of bats why did they choose Pteropus alecto, Myotis davidii etc. This needs more explanation. Title: A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses", "Passage: Bats belong to the order Chiroptera, one of the most abundant, diverse and widely geographically dispersed groups of mammals. This order includes about 1,200 species, accounting for almost 25% of class Mammalia. Interest in these animals is increasing, as they are thought to play an essential role in ecosystem ecology, a domain that has only recently begun to be studied. Bats are highly diverse in terms of their anatomy and lifestyles. Most feed on insects and other arthropods, but some species feed on vertebrates, fish, blood, fruit, nectar or pollen. The order Chiroptera is divided into two suborders: Yinpterochiroptera and", "Title: Technical Description of RODS: A Real-time Public Health Surveillance System\nPassage: provide complete surveillance coverage. Title: Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals", "Passage: When implementing a national response, the problem to be solved, reduced, changed or prevented must first be understood. Surveillance refers to the systematic collection of outcome-specific data \"\u2026for use in the planning, implementation, and evaluation of public health practice\" . Many countries have no or, at best only very basic, systems of surveillance that provide routine suicide data that is collected systematically and that can inform both programmatic targets for interventions and the development of policy initiatives. Significantly, many countries do not know the key methods used for suicide or the proportion of all suicides who have previously made attempts. Title: A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011\u20132012", "Passage: One of the goals of sentinel influenza surveillance is to minimize the impact of disease by providing useful information to public health authorities so that they may better plan appropriate prevention and control measures . An effective influenza surveillance system should also be able to identify novel or emergent pathogens in the community, and promptly alert health authorities about persons most affected in order to better target programmatic responses. For surveillance to be effective, data collection systems should be able to maintain data integrity, quickly provide analysis-ready data, and be sustainable to run. In the last decade, information and communication Title: Improved Global Capacity for Influenza Surveillance\nPassage: influenza disease by using national surveillance data to guide decision making for prevention and control strategies. These development areas are the focus of our evaluation.", "Title: Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data\nPassage: an appropriate uncertainty bound of R 0 . It should be noted that given the knowledge of g s and readily available incidence data, equation permits calculation of the expected value of R 0 without likelihood. Such a calculation can be attained using any spreadsheet. Title: Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data", "Passage: process. In other words, the likelihood function for estimating R 0 is: where T is the most recent time point of observation within an early epidemic growth stage. The maximum likelihood estimate of R 0 is obtained by minimizing the negative logarithm of , and the 95% CI are derived from the profile likelihood. Table 1 shows the estimates of r and R 0 for HIV in France, Western Germany and the UK. The maximum likelihood estimates of r ranged from 1.15 to 2.15 per year with the smallest estimate in France and the highest in Western Germany. The 95% Title: Estimating the number of infections and the impact of non-\nPassage: R0 vs R Title: The Failure of R (0)", "Passage: R0 vs R Title: The Failure of R (0)\nPassage: Summary of R 0 Methods. In summary, there are many methods available for calculating R 0 , but few of them agree with each other and almost none reliably calculate the average number of secondary infections in a wholly susceptible population. The only method which does is the survival function, but this method is too cumbersome to be used except for the simplest of models.", "Title: Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition\nPassage: The ABI Prism 7500 sequence detection system was used for the amplification and detection of the MS2 and Enterovirus RNA by TaqMan technology as previously described . Briefly, for MS2 rRT-PCR, 5 ml of RNA was added to the AgPath Mastermix , which contained the published concentrations of primers and probes and 5-carboxy-X-rhodamine succinimidyl ester as an internal reference dye, whereas 8 ml of RNA was added for all enterovirus rRT-PCR assays. rRT-PCR was performed under the following conditions: 30 min at 48uC, 10 min at 95uC, and 60 cycles of 15 s at 95uC and 1 min at 60uC. Title: Preparation of MS2 Phage-Like Particles and Their Use As Potential Process Control Viruses for Detection and Quantification of Enteric RNA Viruses in Different Matrices", "Passage: Reverse transcription was carried out using PrimeScript Reverse Transcriptase with slight modifications to the manufacturer's protocol. The RT mixture contained 0.5 nmol of dNTP mix , 20,000 molecules of IAC RNA, 2 pmol of both reverse primers , 4 \u00b5l of PrimeScript reaction buffer, 5 U of reverse transcriptase, 1 U of RNase inhibitor and 5 \u00b5l of isolated RNA. The reaction was performed at 50 \u2022 C for 1 h followed by 75 \u2022 C for 15 min and a cooling step at 10 \u2022 C. Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: Total RNA was extracted with Trizol from LCLs. Reverse transcription of 400ng total RNA was performed using AMV reverse transcriptase and random hexamers according to the manufacturer's protocol. SYBR green RT-qPCR analysis was run with the following cycling parameters: 10 min at 95 \u2022 C for initial polymerase activation followed by 40 cycles of 15 s at 95 \u2022 C and 1 min at 60 \u2022 C. The Taqman RT-qPCR experiments were performed using the thermal cycling protocol on the ABI StepOnePlus Real Time PCR System . All samples were run in duplicates and unless stated otherwise the human GAPDH Title: Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics\nPassage: gray. For all amplifications, the thermal cycle conditions began with an initial step at 51\u00baC and 95\u00baC ; followed by 60 cycles at 95\u00baC , 60\u00baC , in an ABI 7500 Thermal Cycler .", "Title: Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures\nPassage: The bearded vulture is one of the most endangered birds in Europe, with a main stronghold in the Pyrenees. Increasing declines in productivity have recently been reported in the Spanish Pyrenees associated with habitat saturation processes . Given that bearded vultures may raise only one fledgling per breeding attempt, this productivity decline should be linked to increasing breeding failure when the proportion of territorial pairs that are breeding does not greatly vary with time . The proximate mechanisms by which density can affect productivity have been investigated, including habitat heterogeneity, with progressively poorer territories being used, territory shrinkage and interference Title: Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures", "Passage: Failed eggs and dead nestlings were collected from bearded vulture nests located in the Spanish Pyrenees between 2005 and 2008. The study of this material did not require of the approval of an ethics committee because it was collected after breeding failure was confirmed in the field. Three of the specimens were collected in 2005, 2007 and 2008 from a particular territory. Eggs and nestlings were collected after breeding failure and frozen. Necropsies were performed on all specimens according to standard protocols . The age of embryos and nestlings were estimated according to size and development. Samples of liver, kidney, Title: Pronounced Seasonal Changes in the Movement Ecology of a Highly Gregarious Central-Place Forager, the African Straw-Coloured Fruit Bat (Eidolon helvum)", "Passage: We built on previous efforts monitoring the size of the bat colony in Accra ). From January 2009 through January 2012, we strived to conduct visual counts on a monthly basis. For this, a single, trained observer walked through the colony during a single day and estimated the number of bats roosting in a cluster, then the number of clusters on each major branch, and continuing this way until all roost trees of the colony were covered. New observers initially estimated colony size in parallel with trained observers, thus ensuring that the same technique was followed and data remained comparable. Title: Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures", "Passage: restricted geographic distribution and low genetic variability common to many threatened species may favour pathogen transmission and reduce the ability of a na\u00efve immune system to fight against novel pathogens , making them especially vulnerable to the potential cross-species transmission of highly virulent virus strains able to cause important outbreaks, as reported in poultry .", "Title: Internal control for real-time polymerase chain reaction based on MS2 bacteriophage for RNA viruses diagnostics\nPassage: Initially, false-positive results, a consequence of reaction contamination with previously generated amplicons, were the main concern of those who were using this new technique. Measures were adopted to avoid contamination with pre-amplified nucleic acids and substantial improvement achieved with the introduction of real-time PCR. This is because real-time PCR is a closed tube system which does not require post-PCR analysis of amplicons; still considered a major source of contamination and false-positive results when executing this technique. Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: Real-time PCR is much more sensitive than other methods of detection and is available for detecting influenza virus but is more expensive. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: realtime PCR method was able to detect 6 cases of SARS-CoV positive samples that were not confirmed by any other assay \u2022 The real time PCR has a threshold sensitivity of 10 genome equivalents per reaction and it has a good reproducibility with the inter-assay coefficients of variation of 1.73 to 2.72%. \u2022 13 specimens from 6 patients were positive with viral load range from 362 to 36,240,000 genome equivalents/mL. The real-time RT-PCR reaction was more sensitive than the nested PCR reaction, as the detection limit for the nested PCR reaction was about 10 3 genome equivalents in the standard Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase\nPassage: All 7 samples were detected as positive by the new method, while only 4 were detected as positive by the conventional method , possibly due to low viral load. This result suggested that the HFman probe-based RT-qPCR has higher sensitivity than the TaqMan probe-based conventional RT-qPCR.", "Title: Genome-Wide Analysis of Codon Usage Bias in Epichlo\u00eb festucae\nPassage: The GC content for the total 4870 genes varies from 46.43%\u02d85.80% to 64.11%\u02d810.16% , with a mean value of 56.41%\u02d84.6% being distributed mainly between 24.80% and 73.00% , the GC12 being distributed mainly between 40.00% and 60.00% . The greatest differences of GC content are found in GC2 and GC3 , where most synoymous mutations occur . Title: Insights into the genetic and host adaptability of emerging porcine circovirus 3", "Passage: Next, we explored if the nucleotide composition has an influence on codon usage bias. The average \u00b1 standard deviation values of nucleotides A and G were 28.31% \u00b1 0.11 and 26.09% \u00b1 0.12, respectively, and more abundant than C and T . However, the nucleotide composition at the third position of synonymous codons were significantly different from the nucleotide composition. The most frequent nucleotide was T 3 , followed by G 3 , C 3 and A 3 . Additionally, the percentage of AT was higher than GC revealing that PCV3 strains are AT rich. The average values of GC Title: Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts", "Passage: The variation in nucleotide content in each codon provides a representation of possible exceptionalism and conservation of particular positions. Methods for exploring GC content variation were as in Tang et al. . For each codon position in codons 2-30, the proportion of each nucleotide usage was calculated across all CDSs in each genome. For each genome, the GC proportion for each position was then calculated across all CDSs. Finally, the variance in GC content at each position between genomes provided an overall GC variance. Title: Analysis of synonymous codon usage and evolution of begomoviruses", "Passage: GC content is the frequency of G+C in a coding gene. GC1, GC2 and GC3 contents are the frequencies of G+C at the first, second and third positions of codons, respectively. A3, T3, G3 and C3 contents are the frequencies of A, T, G and C at the synonymous third position of codons, respectively. Effective number of codons , ranging from 20 to 61, is generally used to measure the bias of synonymous codons. When N c value approaches 20, only one codon is used with extreme bias for one amino acid and, if the value is up to 61,", "Title: SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells\nPassage: Modified viruses were constructed by homologous recombination using fluorescent reporter genes for selection. To generate MVA-SPI-1, a C12L DNA segment was introduced into the genome of MVA at the deletion III site by inserting the DNA fragment downstream of the mH5 promoter in pLW44-derived vector which also contains the P11 VACV promoter driven GFP . The MVA-SPI-1 F322A and MVA-SPI-1 T309R were constructed by mutating the Phe322 into Ala and Thr309 into Arg using Q5 Site-Directed Mutagenesis Kit . Title: Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis", "Passage: Conversely, I622A was found to enhance CD81-LEL binding by 56% and 49%, determined by ELISA and flow cytometry, respectively , while F627A did not affect binding or mildly enhanced binding by 13% . These findings were confirmed by testing the ability of soluble E2c harboring I622A, F627A, or double mutations to bind CD81-Fc and a mutant that reduces CD81 dimerization, i.e. CD81-Fc . Title: SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells\nPassage: The cells were fixed, dehydrated and embedded in Embed 812 resin as described previously . Specimens were viewed with a FEI Tecnai Spirit transmission electron microscope . Title: Endogenous Retrovirus ev21 Dose Not Recombine with ALV-J and Induces the Expression of ISGs in the Host", "Passage: The The sequences of M180 and K243 displayed high nucleotide homology with each other. The env gene of the two isolates showed 94.2-94.8% nucleotide identity to reference ALV-J strains and EAV-HP. These results indicated that M180 and K243 have a closest phylogenetic relationship with ALV-J.", "Title: Results From the First Six Years of National Sentinel Surveillance for Influenza in Kenya, July 2007\u2013June 2013\nPassage: Data from all but two sites were collected using standard paper questionnaires and entered into a Microsoft Access database. At Siaya District Hospital and Tingwang'i Health Center, scannable paper forms were used . Beginning in May 2011 smart phones were used to collect the same demographic and clinical data from patients in five hospitals. Data collected on smart phones were uploaded daily to the KEMRI/CDC server in Kisumu using a secure web link. Data were downloaded from the server onto an MS Access database. We conducted data cleaning to check for inconsistent or illogical data every week. Laboratory data were Title: A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011\u20132012", "Passage: to have electronically collected data available in the database could have further been shortened. Poor network coverage in certain areas within the health facilities necessitated that data be saved in the smartphone's memory and later uploaded into the server at convenient places where there was good network coverage. Occasional server communication breakdowns may have also increased the time taken for this data to be uploaded into the database. Despite these obstacles, our electronic data collection systems still reduced the time needed for routine data to be available for analysis by two weeks. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: Data collection started in August 2016 and was completed in April 2017. Currently , data analysis is ongoing. Title: A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011\u20132012\nPassage: We compared median time from data collection to data entry into central database for the two systems. This was done by determining the date when data was collected and subtracting this from the date when data was entered or uploaded into the data base . The smartphone data collection system initially was not programmed to record the date when data were uploaded; this was however put in place in July 2013. We therefore only used smartphone records collected between July 2013 and September 2013 to assess timeliness of data between the two systems. Wilcoxon signed-rank tests were used to assess", "Title: Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic\nPassage: equation may be a simpler solution. Right censoring is not however the only complication associated with estimating reproduction numbers in practice, and is not completely absent from due to the delay in detecting infections. Left censoring may also arise due to not knowing the baseline number infected if an epidemic has been unfolding for some time before observations are recorded. Finally, estimating the generation time distribution may not be straightforward. Title: Estimating the number of infections and the impact of non-\nPassage: 8.4.6 Starting reproduction numbers vs theoretical predictions Title: Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns", "Passage: and a decrease in the growth of the outbreak . Several methods exist for estimating these quantities either in real time as the epidemic progresses, or after the epidemic is over . Frequently, these estimators assume a homogenously mixing population, even though often this simplifying assumption may not be realistic. One possible source of heterogeneity is the lack of spatial uniformity in transmission across the population in question. In such an instance, the question arises of how to modify our inference-on the reproductive number, for example-and the impact this might have on our understanding of transmission dynamics. Title: Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic", "Passage: The relationship between the idealised generation time distribution w and the distribution of observed generation times can be rather complex for a number of reasons. First, infections are rarely observed, and thus must be either backcalculated or the generation times must be based on a surrogate such as the appearance of symptoms . Second, right censoring can cause the observed generation times to be shorter or longer than expected for a growing or declining epidemic, respectively . Third, as apparent here, if the reproduction number R changes due to depletion of susceptibles, changes in contact rates or public health measures,", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: Viruses are not considered alive by most of the scientific community and as written in textbooks, because they cannot replicate autonomously. Yet some of the giant viruses are equipped with almost all components of the protein synthesis machinery close to bacteria suggesting that they belong to the living matter . The ribozymes may have been the earliest replicating entity. Perhaps also other viruses were initially more independent of the early Earth than they are today. As described in Figure 1 there may have been initially no major difference between an early virus or an early cell. Only later viruses may Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: Efforts have been made to identify the smallest living cell that is still autonomously replicating. Among the presumably smallest naturally occurring bacteria is Pelagibacter ubique of the SAR11 clade of bacteria , which was discovered in 1990. It is an alpha-proteobacterium with 1,389 genes present ubiquitously in all oceans. It can reach up to 10 28 free living cells in total and represents about 25% of microbial plankton cells. Very little of its DNA is non-coding. It harbors podophage-type phages, designated as \"pelagiphage\" . This small bacterium was designated as the most common organism on the planet. Why is it Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: early life must have started simple and with high genetic variability and then became more complex. But complexity can be given up for a less energy consuming lifestyle with small genomes and high speed of replication (Moelling, 2012 (Moelling, , 2013 . Therefore, the question may be repeated: \"Are viruses our oldest ancestors?\" Some fossil life can be partially reproduced in vitro by Spiegelman's Monster and Eigen's follow-up experiments, explaining the great surviving potential of simple ncRNA.", "Title: Estimating the number of infections and the impact of non-\nPassage: study have implemented all major non-pharmaceutical interventions. Title: Estimating the number of infections and the impact of non-\nPassage: interventions. Title: Estimating the number of infections and the impact of non-\nPassage: To understand the impact of interventions, we fit a counterfactual model without the interventions Title: Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus", "Passage: Impact of epidemic interventions is usually quantified by mathematical models. Clinical trial design is impractical for assessing the effectiveness of some interventions, such as face masks and isolation, because of ethical considerations relating to epidemics in general. By using mathematical models, the epidemic dynamics and intervention effectiveness can be determined. Such models can evaluate a range of interventions; isolation , quarantine , antiviral drugs , school closures http://www.biomedcentral.com/1471-2334/12/309 , vaccinations and face masks , among others.", "Title: Outdoor environments and human pathogens in air\nPassage: Detection and identification of pathogens has changed since the development of different molecular methods and innovative approaches other than culture methods . The existing detection methods can be divided into two levels: generic and specific. Generic detection gives information about whether the particles are biological materials, microbes or living cells, e.g. bioluminescent measurement of ATP using continuous flow luminometer and mass-spectrometry. Specific methods such as micro-arrary and immuno-assays can tell us what kind of microbes are detected and identified. Other new techniques have been proposed for bio-detection, for instance, by characterising the size and shape of bioaerosols, pollens and fungal Title: The Microbial Detection Array Combined with Random Phi29-Amplification Used as a Diagnostic Tool for Virus Detection in Clinical Samples", "Passage: A common method of choice for clinical pathogen identification is polymerase chain reaction which is a sensitive and specific method. However, each PCR reaction only provides identification of one specific virus, or a group of related viruses. Thus, a clinical hypothesis regarding the suspected pathogen needs to guide the decision as to which PCR analyses to perform, resulting in a large number of PCR protocols needed to facilitate the identification of all human pathogens. Title: Viral infection detection using metagenomics technology in six poultry farms of eastern China", "Passage: Animal disease surveillance is fundamental for animal disease prevention and control, and it is also a tool to get the information used to make decisions about control and eradication strategies. A variety of laboratory techniques have been used to survey the epidemiology of animal infectious diseases, among which animal pathogen surveillance and tracking the molecular epidemiology of pathogens are important strategies . These methods usually involve pathogen isolation and identification, reverse transcription-polymerase chain reaction , real-time RT-PCR, and sequencing analyses. These methods often target a single known a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 pathogen; however, the analysis of multiple pathogens in Title: Massively parallel pathogen identification using high\u2010density microarrays", "Passage: Current methods for pathogen identification possess a number of advantages and shortcomings with respect to clinical utility. For example, nucleic acid detection by quantitative PCR is extremely rapid and sensitive, but provides simultaneous results on a limited number of primer pair-determined genomic regions. In contrast, traditional culture-based, phenotypic methods are often limited by lengthy incubation periods, but allow for the identification of multiple pathogens and are currently considered the gold standard in clinical microbiology laboratories.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Arden KE. Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd. Virus Res 2015 Vol 202:60-88 with permission from Elsevier DCs, which make up 95 % of all camels, have a central presence in the Arabian Peninsula where human-DC contact ranges from little to close . Contact may be commonplace and could occur in variety of ways . There are several large well-attended festivals, races, sales and parades which feature DCs and DCs are also kept and bred close to populated areas in the KSA . DC milk and meat are widely consumed and the older DC Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In the region of Ar Riyad, including the capital city of Riyadh, a hospital based cluster began, within a single hospital, from late June 2015 . By mid-September there had been approximately170 cases reported but the outbreak appeared to been brought under control in November.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: cold symptoms than placebo treated patients in the intention-to-treat population . The anti-influenza activity was shown by subgroup analysis of 49 influenza infected patients who benefited from a 3.3 days faster recovery from symptoms. The use of carrageenan nasal spray was associated with a significant reduction of the influenza viral load in nasal fluids and a significant increase in the number of virus free patients within the treatment period of 7 days. In good accordance Prieschl-Grassauer are co-founders of Marinomed Biotechnologie GmbH. Marinomed Biotechnologie GmbH had a role in study design, data collection and analysis, decision to publish, preparation of Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: to the broad antiviral effectiveness of carrageenan, patients will receive in parallel a treatment of concomitant viral infections. Therefore, patients will benefit from a decreased probability to develop complications. In consideration of the complications known to accompany an influenza virus illness this combinational therapy meets an urgent medical need. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: A nasal spray containing carrageenan together with Zanamivir provides an easy to apply treatment of upper respiratory tract infections in patients under suspicion to be influenza infected. Patients would benefit from the fast and efficient treatment of uncomplicated influenza in the upper respiratory tract. Due to the faster influenza virus clearance from the upper respiratory tract and the independent antiviral mechanism of carrageenan and Zanamivir the likelihood to develop escape mutations against Zanamivir will be reduced. Both individual compounds are able to reduce severity and/or duration of the influenza illness and a combination is expected to work similarly. Additionally, due Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is", "Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\".", "Title: Coinfection and Mortality in Pneumonia-Related Acute Respiratory Distress Syndrome Patients with Bronchoalveolar Lavage: A Prospective Observational Study\nPassage: Acute respiratory distress syndrome is defined as an acute inflammatory lung injury associated with increased pulmonary vascular permeability, decreased lung compliance, and bilateral lung infiltrates and hypoxemia . Several factors increase the risk of ARDS, including sepsis, aspiration, major trauma, pulmonary contusion, acute pancreatitis, drug, massive transfusions, pulmonary vasculitis, and drowning , with pneumonia being the most common risk factor, reported in 33% to 59% of cases . Furthermore, pneumonia is the only infection associated with an increased risk of developing ARDS in critically ill patients . Title: Sequelae of Acute Respiratory Distress Syndrome: Interest of Rehabilitation", "Passage: Acute respiratory distress syndrome accounts for 10.4% of intensive care admissions and is associated with high mortality, between 34.9 and 46.1% depending on the severity . ARDS is a multifactorial syndrome characterized by new or worsening symptoms during 1 week, bilateral opacities , the ratio of arterial oxygen tension to fraction of inspired oxygen less than 300 mm Hg with positive end-expiratory pressure or continuous positive airway pressure of 5 cm H 2 O or more, and no clinical evidence of heart failure or fluid overload . It causes physiological alterations: alteration of pulmonary thoracic compliance, intra-lung shunt, and alveolar Title: Pathophysiology and biomarkers of acute respiratory distress syndrome", "Passage: 2011, a draft of a revised definition was presented at the 24th Annual Congress of the European Society of Intensive Care Medicine in Berlin, and its final version was published in JAMA in May 2012 . In the revised Berlin definition, the term ARDS was redefined as a broader concept including a milder condition of lung injury; therefore, it became equivalent to acute lung injury , which was the previous AECC definition. Title: Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice", "Passage: distress syndrome . Many studies have shown that ARDS caused by 2009 H1N1 virus results in 17.3-56% mortality , which was regarded as the major cause of death by 2009 H1N1 virus infection . ARDS is the result of acute injury to lung tissue, commonly resulting from sepsis, trauma, and severe pulmonary infections . Infectious factors, most of which are viruses, have become one of the most important causes of ARDS in humans . Clinical cases and established animal models have revealed that the pathogenesis and pathological features of ARDS induced by different viral pathogens are distinct . However, knowledge", "Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: Text: Influenza like-illness or acute respiratory infections can be caused by several types of respiratory viruses or bacteria in humans . Influenza viruses, Respiratory Syncytial viruses and Parainfluenza viruses are identified as major viruses mostly responsible for ILI and pneumonia in several studies . However practitioners cannot diagnose the infection without a biological test confirmation. Unfortunately, these infections causes are identified in less than 50% . Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France", "Passage: Among H1N1v negative single infections, the most prevalent viruses were rhinovirus , followed by parainfluenza viruses 1 to 4 , adenovirus , human coronavirus 229E, OC43 and NL63 and respiratory syncytial virus A and B . In addition, RespiFinder19H assay identified three patients with bacterial infection, two with Mycoplasma pneumoniae and one with Bordetella pertussis . No single infection by influenza B, hMPV, Chlamydophila pneumoniae or Legionella pneumophila was identified . Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: This retrospective study based on a sentinel GPs network showed that not only influenza viruses are responsible for ILI consultations. Indeed, an important circulation of multiple pathogens was observed throughout the year, with 12 different types of pathogens identified in 2011 and 2012. Respiratory viral pathogens were present in 76.1% of samples, which is largely above results from annual influenza surveillance . After influenza viruses, Rhinovirus and Coronavirus were the most common respiratory viruses in R\u00e9union Island. Although samples were not taken every week, sample was representative of ILI activity and consistent with flu season. Nevertheless, according to the low Title: Epidemiology and Viral Etiology of the Influenza-Like Illness in Corsica during the 2012\u20132013 Winter: An Analysis of Several Sentinel Surveillance Systems", "Passage: In the present study, the rate of positivity for at least one respiratory virus decreased significantly with age. It should be noted that while human respiratory syncytial virus , was the second most frequently detected respiratory virus after influenza in patients aged less than 15 years, in agreement with previous studies , HRV was the most frequently detected virus in patients aged .65 years. Information about the non influenza viral infections such as HRV to ILI episodes in older persons is poor, partly because of difficulties in diagnosis related to atypical presentations and low viral loads . Previously, it has", "Title: MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice\nPassage: JEV SA-14 strain was propagated in the mosquito cell line C6/36. The supernatant containing JEV was concentrated as follows, the supernatant of JEV-infected C6/36 cell was collected and centrifuged at 8,000 g for 30 min at 4 \u2022 C to remove the cell debris. Next, the supernatant was ultra-centrifuged at 40,000 g for 4 h at 4 \u2022 C and the viral pellet was resuspended with PBS at 100:1 after removing the supernatant thoroughly. After being filtered through 0.22 \u00b5m filters, the virus suspension was titrated by conventional plaque assay and stored at \u221280 \u2022 C . Title: The role of viral persistence in flavivirus biology", "Passage: For JEV, the major amplifying hosts are birds and pigs, which attain high levels of viremia. They provide a source of infection for the mosquito species that subsequently transmit JEV to humans . JEV control has been achieved through vaccination of pigs and humans in Korea, Japan, and Taiwan while horses are considered dead-end hosts of JEV infection due to a very low level of viremia. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection\nPassage: infection effectively. Similarly, treatment with the cell-permeant Ca 2\u03e9 chelator 1,2-bis--ethane-N,N,N=,N=-tetraacetic acid, tetraacetoxymethyl ester , could also suppress JEV infection. Taken together, we concluded that intracellular Ca 2\u03e9 is essential for JEV infection and cytoplasmic calcium is a potent target for antiflavivirus treatment. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: infection effectively. Similarly, treatment with the cell-permeant Ca 2\u03e9 chelator 1,2-bis--ethane-N,N,N=,N=-tetraacetic acid, tetraacetoxymethyl ester , could also suppress JEV infection. Taken together, we concluded that intracellular Ca 2\u03e9 is essential for JEV infection and cytoplasmic calcium is a potent target for antiflavivirus treatment.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: to the ANFIS parameters to enhance time series forecasting because these parameters have a significant effect on the performance of ANFIS. The SI methods include the particle swarm optimization , social-spider optimization , sine-cosine algorithm , and multi-verse optimizer . For example, in SCA algorithm was applied to improve the ANFIS model to forecast oil consumption in three countries, namely, Canada, Germany, and Japan. In the same context, in , The MVO algorithm was used to enhance the ANFIS model to forecast oil consumption in two countries. In addition, in the PSO was used with ANFIS to predict biochar yield. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: However, individual SI algorithms may stock at local optima. Therefore, one solution is to apply hybrid SI algorithms to avoid this problem. In , a hybrid of two SI algorithms, namely GA and SSA, was presented to improve the ANFIS model. The proposed new model called GA-SSA-ANFIS was applied to forecast crude oil prices for long-term time series data. However, the previously mentioned methods suffer from some limitations that can affect the performance of the forecasting output such as slow convergence and the ability to balance between exploration and exploitation phases can influence the quality of the final output. This Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: In the current study, we propose an improved ANFIS model based on a modified flower pollination algorithm using the salp swarm algorithm . The FPA is an optimization algorithm proposed by Yang , which was inspired by the flow pollination process of the flowering plants. The FPA was employed in various optimization applications, for example to estimate solar PV parameter , solving sudoku puzzles , feature selection , antenna design , and other applications . Moreover, SSA is also an optimization algorithm proposed by Mirjalili et al. inspired by the behavior of salp chains. In recent years, the SSA was Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: algorithm . In general, SSA is employed to improve FPA to avoid its drawbacks . The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error , Root Mean Squared Relative Error , Root Mean Squared", "Title: Estimating the number of infections and the impact of non-\nPassage: recent trends in deaths in several countries, where the rate of increase had clearly slowed . Title: Estimating the number of infections and the impact of non-\nPassage: We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact Title: Estimating the number of infections and the impact of non-\nPassage: lag between infections and deaths, continued rises in daily deaths are to be expected for some time. Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: Projected changes in numbers of deaths may be due to changes in age-specific disease and injury death rates, or due to demographic changes that alter the size and age composition of the population, or both. Death rates are strongly age dependent for most causes, so changes in the age structure of a population may result in substantial changes in the number of deaths, even when the age-specific rates remain unchanged.", "Title: Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers\u2019 Understanding to Improve Health Care\nPassage: Japanese encephalitis is a serious illness caused by the Japanese encephalitis virus. Specifically, it is caused by the mosquito borne JE flavivirus. JE is the leading cause of viral encephalitis and disability in Asia. Solomon and colleagues reported that approximately 30,000-50,000 cases of JE are reported each year with an estimation of about 10,000 deaths annually . According to World Health Organization report, approximately 3 billion people are living in countries, which are at risk of JE in Southeast Asia and Western Pacific . Children under 15 years of age are the major target of this fatal disease. Researchers reported Title: Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers\u2019 Understanding to Improve Health Care", "Passage: between mosquitoes and hosts like pigs and/or birds. Transmission of JE virus is predominant in rural agricultural areas, often associated with rice cultivation and flooding irrigation . Therefore, outbreaks are mainly associated with the rainy period which falls in summer and fall season in India . Title: Comprehensive Mapping Antigenic Epitopes of NS1 Protein of Japanese Encephalitis Virus with Monoclonal Antibodies", "Passage: Japanese encephalitis is caused by the Japanese encephalitis virus , and is one of the most important mosquito-borne diseases with a mortality rate as high as 20% to 50%, and is widely distributed in most of East and South-east Asia and parts of Oceania. Up to 50,000 human cases of JE are reported annually in Asian countries, of which 10,000-15,000 result in fatality . A high proportion of survivors, especially young children and those greater than 65 years of age, exhibit permanent neurologic and psychiatric sequelae. A wide range of animals including swine, equines and birds can also be infected. Title: Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses", "Passage: Japanese encephalitis is an acute zoonotic, mosquitoborne disease caused by JE virus , a single-stranded, positive-sense RNA virus belonging to the family Flaviviridae and the genus Flavivirus . Infection with neurotropic flaviviruses of the JE serotype, which include JE, Murray Valley encephalitis, St. Louis encephalitis, and West Nile virus , results in debilitating neurological disorders in a significant proportion of clinical cases . JE is a leading cause of viral encephalitis manifested by extensive neuroinflammation in the central nervous system and disruption of the blood-brain barrier . In humans, the clinical presentation of JEV infection ranges from mild febrile illness", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2 . Poxviruses are also studied extensively as candidate vectors for human use, among which attenuated derivatives of vaccinia virus and New York attenuated vaccinia virus NYVAC strains] are the most promising vectors . They are ideal candidate vectors due to their large DNA-packing capacity and their thermal and genetic stability . The NYVAC vector has been shown to induce CD4 + T cell-dominant responses, and MVA induces Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: and Listeria monocytogenes are preferable carriers for DNA vaccines. is not yet fully understood for many species. The suggested mechanism is based on the bacterial invasion properties . Thus, some invasive bacteria, such as Salmonella typhimurium and Listeria monocytogenes are preferable carriers for DNA vaccines. , and inside the DCs, the antigen gene is expressed as protein, which will later be presented by class I or II MHC and delivered to CD4+ or CD8+ T cells. Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: has a hyper invasive phenotype that can invade the host cell, escape the endosomes, and reduce the bacteria apoptosis. As a consequence, the DNA is allowed to efficiently enter the nucleus . Several other manipulations have been studied to improve the ability of Salmonella spp. as a vaccine carrier, including the manipulation of lipid A, outer membrane vesicles and engineering the dual-plasmid system, as described briefly by Wang et al. . Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: carrier.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: NDV has also been explored as a vaccine vector for humans. Two NHP studies assessed the immunogenicity and efficacy of an rNDV expressing the HA or NA of A/Vietnam/1203/2004 . Intranasal and intratracheal delivery of the rNDV-HA or rNDV-NA vaccines induced both serum and mucosal antibody responses and protected from HPAIV challenge . NDV has limited clinical data; however, phase I and phase I/II clinical trials have shown that the NDV vector is well-tolerated, even at high doses delivered intravenously . While these results are promising, additional studies are needed to advance NDV as a human vaccine vector for influenza. Title: Viral vector-based influenza vaccines", "Passage: one single study, cross-reactive cellular immune responses against A viruses were observed after vaccination with a NDV-H5 construct. 168 The immunogenicity of recombinant NDV expressing the HA and NA genes of influenza virus A/Vietnam/1203/04 was tested in non-human primates. Both constructs induced VN and local IgA antibody responses and afforded protection from A challenge infection. 169, 170 Small numbers of clinical trials have been performed with NDV, which showed that the vector is well tolerated. Title: Viral vector-based influenza vaccines", "Passage: Newcastle disease virus is a single-stranded negative sense RNA paramyxovirus that causes disease in poultry. NDV has several favorable properties as a vaccine vector; no preexisting immunity in humans exists, NDV can easily be attenuated and reverse genetics systems to rescue recombinant NDV are in place. Thus far, NDV has been extensively characterized as an influenza vaccine vector in poultry, where it serves as a bivalent vaccine capable of inducing immunity against both NDV and influenza virus. As an added advantage, NDV is easily administered to poultry through nasal spray, drinking water or ocular drops. An overview of NDV-based influenza Title: Viral vector-based influenza vaccines", "Passage: The first study using NDV as a vaccine vector for influenza was NDV-H1, that expressed the HA gene of influenza virus A/ WSN/1933. Complete protection of mice against homologous challenge infection was achieved, demonstrating that NDV can be used as an influenza vaccine vector. 148 Consequently, a recombinant NDV expressing HA genes of A viruses has been licensed as a poultry vaccine in some countries and was shown to have a protective effect against challenge infection with A viruses in chickens and ducks in various studies. The NDV based A vaccine offered only partial cross-clade protection, but was immunogenic in", "Title: Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study\nPassage: Fifty-one patients were identified in the acute lung injury screening database between September 2009 and March 2010. Twenty-two met criteria for ALI and did not have confirmed or suspected H1N1 infection and were thus included in the noninfluenza group . Thirty-six patients in the H1N1 patient log had confirmed influenza A testing. Of those, 23 had ALI requiring mechanical ventilation during their MICU stay and were included in our analysis. Title: Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study", "Passage: infection were included in the influenza group to ensure that the clinical course of the disease was accurately captured. Patients were excluded from the study if they did not meet the above criteria for ARDS, or if clinical suspicion pointed to a likely pandemic viral infection with negative diagnostics. Title: Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study", "Passage: In accordance with other descriptive reports of pandemic influenza , patients who tested positive for H1N1 infection, tended to be young , obese , and in relatively good health . There were no pregnant patients in either group. Compared with other studies of pandemic influenza patients who required mechanical ventilation, SOFA scores were similar, although APACHE II scores were higher 14, 16, 17, 23] . The degree of respiratory compromise in our patients was more severe than other reports judging by the higher PEEP requirements and longer duration of mechanical ventilation, which was roughly double that reported in other studies Title: Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study", "Passage: The spread of a novel H1N1 strain of the Influenza A virus represents the first pandemic of the 21 st century and the first influenza pandemic since 1968 . Compared with seasonal influenza, this strain was more prevalent in younger-aged individuals, obese patients, and pregnant women . Severe cases of pandemic H1N1 resulted in respiratory failure thought to be secondary to direct cell damage and systemic cytokine release resulting in acute lung injury or acute respiratory distress syndrome requiring prolonged ventilatory assistance and the frequent use of rescue therapies .", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: are not of sufficient magnitude to constitute primary end-point consolidation, and small areas of atelectasis that in children can be difficult to distinguish from consolidation. \"Primary end-point pneumonia\" included either end-point consolidation or a pleural effusion associated with a pulmonary parenchymal infiltrate . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Chest radiologic changes have been considered the gold standard for defining a pneumonia event because clinical findings can be subjective and clinical definitions of pneumonia can be nonspecific. In 2005, to aid in defining outcomes of pneumococcal vaccine studies, the World Health Organization's standardized chest radiograph description defined a group of children who were considered most likely to have pneumococcal pneumonia . The term \"end-point consolidation\" was described as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung. \"Other infiltrate\" included linear and patchy densities, peribronchial thickening, minor patchy infiltrates that Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: one pre-pneumococcal conjugate vaccination study, only 34% of children hospitalized with pneumonia had primary end-point pneumonia . A revised case definition of \"presumed bacterial pneumonia\" has been introduced, and this definition includes pneumonia cases with WHO-defined alveolar consolidation, as well as those with other abnormal chest radiograph infiltrates and a serum C-reactive protein of at least 40 mg/L . This definition has been shown to have greater sensitivity than the original WHO radiologic definition of primary end-point pneumonia for detecting the burden of pneumonia prevented by pneumococcal conjugate vaccination . Using the revised definition, the 10-valent pneumococcal conjugate vaccine , Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort", "Passage: Chest radiograph appearances were recorded as lobar consolidation in 43.7%, patchy localised consolidation in 25.0% and diffuse, bilateral changes in 29.3%.", "Title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection\nPassage: Hepatitis C virus is a positive-stranded RNA virus in the family Flaviviridae, and it is estimated 130-170 million people are infected with HCV worldwide . Acute HCV infection is spontaneously cured in 20%-30% of patients, but the majority of infected patients fail to clear the virus and develop chronic persistent infection . In addition to a combination regimen of pegylated interferon -\u03b1 and ribavirin, direct acting antiviral drugs against HCV have been developed, and a high rate of sustained virological response has been achieved by using these antiviral drugs . However, the high cost of these drugs results in limited Title: Transcriptional response to hepatitis C virus infection and interferon\u2010alpha treatment in the human liver", "Passage: The endogenous activity of the IFN system is also highly relevant for therapeutic choice in chronic hepatitis C . Until the recent introduction of direct antiviral drugs for the treatment of CHC, recombinant pegylated IFN-alpha 2 had been an essential component of the standard of care for CHC for over 25 years, and it is still used in many parts of the world. Treatment with pegIFN-a and ribavirin achieved cure rates between 30 and 80%, depending on the viral genotype, pre-treatment patient history, and stage of liver fibrosis . The success of the treatment is also highly dependent on the Title: Transcriptional response to hepatitis C virus infection and interferon\u2010alpha treatment in the human liver", "Passage: The study included 25 patients with chronic hepatitis C and six control patients who underwent a diagnostic liver biopsy in the outpatient clinic of the Division of Gastroenterology and Hepatology, University Hospital Basel. The patients agreed to participate in the study and written informed consent was obtained . All patients with CHC were screened for potential response to treatment using a previously published classification method based on the expression values of IFI27, RSAD2, ISG15, and HTATIP2 . Patients with high probability of achieving sustained virologic response were identified, and in case of planned IFN-based treatment, they were asked to undergo Title: Advanced Molecular Surveillance of Hepatitis C Virus", "Passage: The arrival of the second generation of direct-acting antivirals in 2011 resulted in improved SVR and a revolution in the field of anti-HCV therapy. Despite the development of drug resistance, the initial NS3-4A protease inhibitors telaprevir and boceprevir undoubtedly possessed advantages over dual IFN/RBV treatment . The success of both drugs was subsequently eclipsed by the licensing of simeprevir and sofosbuvir . The field of HCV therapy is rapidly evolving, and as a result, a large number of new antiviral drugs are currently being evaluated in advanced clinical trials .", "Title: Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function: an experimental study in healthy children and adults\nPassage: APS covers the diameter range~700 nm to 5000 nm. The aerodynamic size is the most appropriate equivalent size determining the lung deposition of particles >500 nm, for which the main deposition mechanisms are impaction and gravitational settling. Title: Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function: an experimental study in healthy children and adults", "Passage: Apart from the variables associated with component 2, airway resistance measured with impulse oscillometry was also investigated, and results in significant improvements to modelled DF for some particle sizes. The best correlation was achieved for the resistance measured at 5 Hz . Including R5 in the multivariate regression analysis improved the model for all size intervals, but was significant only for 30-100 nm particles in the adult group. When including the children, R5 became significant in most size intervals. Title: Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function: an experimental study in healthy children and adults\nPassage: also since they both may reflect the general size of the respiratory tract. Title: Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function: an experimental study in healthy children and adults", "Passage: particles T A and V A were significant, but V TA /V T was stepping in with an even higher level of explanation, while for particles >2.7 \u03bcm only R5 was significant. In the new analysis R5 was no longer significant for the smaller particles, as it was in the previous analysis when looking at the whole group.", "Title: Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data\nPassage: priors on February 7th, the forecast of epidemic size was 47,200 in Martinique, much closer to the final count of 37,400 observed cases at the end of the epidemic in this island. Title: Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data", "Passage: The timecourse of the ZIKV epidemics in Guadeloupe, Martinique and Saint-Martin between December, 2015 and February, 2017 differed markedly: the initial growth was early and sudden in Martinique, while it was delayed in Guadeloupe and Saint-Martin, starting only after four months of low-level transmission . The epidemic showed a sharp peak in Guadeloupe, reaching a maximal weekly incidence of 6.9 cases per 1,000 inhabitants 9 weeks after the start of the period of high epidemic activity. In Martinique and Saint-Martin, weekly incidence reached a maximum of 4.8 cases per 1,000 inhabitants after a period of 10 and 21 weeks, respectively. Title: Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture\nPassage: end of the epidemic varied from the 38 th week to the 44 th week in 2010 and from the 26 th week to the 28 th week in 2011. Title: Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data", "Passage: Surveillance data on the 2015-2017 ZIKV epidemics in Guadeloupe, Martinique and Saint-Martin was collected by local sentinel networks of general practitioners and reported weekly by the local health authorities . Cases of ZIKV infection were defined as \"a rash with or without fever and at least two signs among conjunctivitis, arthralgia or edema\". We obtained numbers of suspected cases by week for each island, extrapolated from the number of active sentinel sites ). In the West Indies, local health authorities described the situation as \"epidemic\" when incidence was larger than 1 per 2,000 population per week , and 20 cases", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The key limitations of genetic material detection are the lack of knowledge of the presence of viable virus, the potential cross-reactivity with non-specific genetic regions and the short timeframe for accurate detection during the acute infection phase. The key limitations of serological testing is the need to collect paired serum samples from cases under investigation for confirmation to eliminate potential cross-reactivity from non-specific antibodies from past exposure and/or infection by other coronaviruses. The limitation of virus culture and isolation is the long duration and the highly specialized skills required of the technicians to process the samples. All patients recovered. Title: Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies", "Passage: insufficient for predicting which influenza strains will mutate into HPAI variants . Despite significant efforts being put into the development of avian vaccines, serological surveillance represents one of the major tools for evaluating the immune state of avian populations especially for the ability of certain subtypes 2 Journal of Immunology Research to mutate due to their longterm circulation among vaccinated populations . Serology represents a powerful and sensitive approach for detecting the presence of avian influenza antibodies in a population but the occurrence of antigenic drift and shift must be taken into consideration as it can render subtype-specific serologic tests Title: Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016", "Passage: no commercial serology test had been accepted for procurement through the WHO Emergency Use Assessment and Listing procedure, which requires extensive validation . This illustrates the importance of reference laboratory capacity. Virus neutralisation is still considered the most specific flavivirus serology test, although cross-reactivity can be observed in patients with other flavivirus infections and research is ongoing to develop more specific assays . Broad implementation of this confirmatory test in EU/EEA national reference laboratories is, however, expected to increase the reliability of serology results in returning travellers as the flavivirus background in European travellers is likely to be low. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Serological testing such as ELISA, IIFT and neutralization tests are effective in determining the extent of infection, including estimating asymptomatic and attack rate. Compared to the detection of viral genome through molecular methods, serological testing detects antibodies and antigens. There would be a lag period as antibodies specifically targeting the virus would normally appear between 14 and 28 days after the illness onset . Furthermore, studies suggest that low antibody titers in the second week or delayed antibody production could be associated with mortality with a high viral load. Hence, serological diagnoses are likely used when nucleic amplification tests are", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: In summary, 2019-nCoV is a novel lineage B Betacoronavirus closely related to bat SARS-related coronaviruses. It also has unique genomic features which deserves further investigation to ascertain their roles in viral replication cycle and pathogenesis. More animal sampling to determine its natural animal reservoir and intermediate animal host in the market is important. This will shed light on the evolutionary history of this emerging coronavirus which has jumped into human after the other two zoonotic Betacoroanviruses, SARS-CoV and MERS-CoV. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The 2019 novel coronavirus , a betacoronavirus, forms a clade within the subgenus sarbecovirus of the Orthocoronavirinae subfamily . The severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus are also betacoronaviruses that are zoonotic in origin and have been linked to potential fatal illness during the outbreaks in 2003 and 2012, respectively . Based on current evidence, pathogenicity for 2019-nCoV is about 3%, which is significantly lower than SARS-CoV and MERS-CoV . However, 2019-nCoV has potentially higher transmissibility than both SARS-CoV and MERS-CoV .", "Title: The interconnected and cross-border nature of risks posed by infectious diseases\nPassage: The consequences of further international spread are particularly acute today given the large number of polio-free but conflict-torn and fragile States which have severely compromised routine immunization services and are at high risk of re-infection. 14 Complicating the matter even further is the fact that alongside broader political issues that affect the possibility of implementing vaccination programmes, personal beliefs about the safety and benefits of vaccines are modulated by social ties, religious beliefs, and familial values. All of these factors affect vaccination uptake rates, as recent studies in both Pakistan and Nigeria have shown . Title: Between Scylla and Charybdis: reconciling competing data management demands in the life sciences", "Passage: It is important to note that these situations may not be \"true\" ethical problems, but instead \"wicked problems\" in that they are difficult to solve because of incomplete or contradictory requirements, rather than inherent conflict . Nonetheless, the inability for scientists to act according to all the responsibilities assigned to them can cause 'ethical erosion, ' , meaning that the sustained inability to act according to the ethical expectations set out in regulations, policy or teaching may cause scientists to cease to see value in the ethics guidelines and act unethically . These issues are thus very important to consider Title: Consequences of delays and imperfect implementation of isolation in epidemic control", "Passage: Of major concern is what happens if the response capability is inadequate, that is, if the isolation probability falls below the required minimum, or if the required identification time is not met. Our next result addresses this scenario. Title: Between Scylla and Charybdis: reconciling competing data management demands in the life sciences\nPassage: Flu, rapid globalization, and increasingly international terrorist groups such as al Qaeda have all contributed to the emergence of this discourse. 4 These experiments of concern were identified as research that could:", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: Viral vector-based influenza vaccines\nPassage: vaccine efficacy. Currently, as alternatives, non-human adenoviruses 190, and low-prevalent adenoviruses 195 are being explored as novel vaccine vectors. Title: Viral vector-based influenza vaccines", "Passage: In the future, more novel vector-based influenza candidate vaccines will be developed and tested in clinical trials. There is potential for improvement by the modification of viral antigens, like the 'headless' or 'shielded' HA constructs, to broaden the reactivity of vaccine induced antibodies. In addition to modifying influenza virus antigens, post-translational modifications and modifications to promoter sequences could also alter and improve the immunogenicity. 226, 227 The biggest challenge of taking vector-based vaccines to the market may be obtaining approval from the regulatory authorities. Only when their safety and superiority over existing vaccine formulations have been demonstrated, implementation of these Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is strong safety and efficacy data for use of NYVAC or MVA-vectored influenza vaccines, preexisting immunity remains a concern. Although the smallpox vaccination campaign has resulted in a population of poxvirus-na\u00ef ve people, the initiation of an MVA or NYVAC vaccination program for HIV, influenza or other pathogens will rapidly reduce this susceptible population. While there is significant interest in development of pox-vectored influenza virus vaccines, current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains. This would likely limit the use and/or efficacy of poxvirus-vectored influenza virus vaccines for regular and seasonal use", "Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC\nPassage: Of note, EV-A71, which came up in the last decade as a major cause of Hand-Foot-Mouth-Disease and viral encephalitis in the Asia-Pacific region , is also a common agent of respiratory disease. Associated to pharyngitis, bronchiolitis, croup and pneumonia, EV-A71 infections mostly affect young children . In addition, cases of acute pulmonary edema have been associated to severe EV-A71 encephalitis, but these are believed to result from the destruction of medullary vasomotor and respiratory centers even if the exact pathogenesis is not completely understood . Title: Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017", "Passage: Text: E choviruses are members of the Enterovirus B species of the Enterovirus genus in the Picornaviridae family of nonenveloped, single-stranded, positive-sense RNA viruses. Echoviruses were named from the acronym enteric cytopathic human orphan virus at the time of their discovery in the 1950s but were later found to be associated with respiratory illness, hand-foot-and-mouth disease, and aseptic meningitis, similar to other enteroviruses . Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: strains have now been reclassified as EV-D68 type . Rarely observed until the late 2000s, a few clusters of EV-D68 cases were progressively reported in different parts of the world during the last decade and associated with mild to severe respiratory illness . During autumn 2014, the USA experienced the largest outbreak of EV-D68 with an unprecedented level of circulation nationwide, especially in the pediatric population. A total of 1153 individuals in 49 states and the District of Columbia tested positive for this virus, mostly children, many with a previous history of wheezing or asthma . Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: Concurrently with its respiratory tropism, EV-D68 infections have been increasingly associated with neurologic disease , including cases of acute flaccid myelitis, thus suggesting a link between EV-D68 and this type of complications . In one case, EV-D68 neurotropism was confirmed by detection of the virus in the cerebrospinal fluid and brain at autopsy of a 5-year-old boy with fulminant encephalitis . EV-D68 was also detected in a blood sample of a child with acute flaccid paralysis . However, although many epidemiological and clinical factors suggest this association , the direct causality link between EV-D68 and neurological involvement has never been", "Title: Responding to the COVID-19 pandemic in complex humanitarian crises\nPassage: Text: Over 168 million people across 50 countries are estimated to need humanitarian assistance in 2020 . Response to epidemics in complex humanitarian crisessuch as the recent cholera epidemic in Yemen and the Ebola epidemic in the Democratic Republic of Congois a global health challenge of increasing scale . The thousands of Yemeni and Congolese who have died in these years-long epidemics demonstrate the difficulty of combatting even well-known pathogens in humanitarian settings. The novel severe acute respiratory syndrome coronavirus-2 may represent a still greater threat to those in complex humanitarian crises, which lack the infrastructure, support, and health systems Title: Responding to the COVID-19 pandemic in complex humanitarian crises\nPassage: Date: 2020-03-21 Title: Sounding the Alarm: Health in the Anthropocene", "Passage: Date: 2020-03-21 Title: Sounding the Alarm: Health in the Anthropocene\nPassage: The misery of most of the population in Syria can be conceptualized as a \"sentinel\", a case study that may provide a glimpse into a dystopian future in which drought, aquifer depletion, and intractable local differences drive conflict. Although Germany has recently led Europe in giving hope to over a million refugees, many from Syria, who are being resettled its generosity is proving to be bounded. Europe is now following the example set by Australia in impeding routes to resettlement, even for people who have a right in international law to seek and be granted asylum. Title: Influenza in Refugees on the Thailand\u2013Myanmar Border, May\u2013October 2009", "Passage: Of 15.2 million refugees worldwide, approximately one third live in camps . These refugees often live in crowded conditions and have contact with populations from the host country and the country of origin, where public health infrastructure and surveillance may be poor .", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: All hospitalised cases had a benign clinical evolution except four, two reported in Italy and two reported in France, all of whom developed viral pneumonia. All three cases who were aged 65 years or over were admitted to intensive care and required respiratory support and one French case died. The case who died was hospitalised for 21 days and required intensive care and mechanical ventilation for 19 days. The duration of hospitalisation was reported for 16 cases with a median of 13 days . As at 21 February 2020, four cases were still hospitalised. Title: Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness", "Passage: Limitations of our study include the retrospective design and the institutional differences in pertussis diagnostics, diagnostics for coinfections, and registration of clinical and laboratory disease characteristics. The 50% participation rate of hospitals might have influenced our results, but participating hospitals were spread over the country and showed a good representation of tertiary, top clinical, and local hospitals in the Netherlands. Results might have been influenced by the incomplete reporting of hospital diagnoses at discharge, assessed in a recent capture-recapture analysis . We could not stratify this underreporting by GA, but the good representation of tertiary, top clinical, and local hospitals Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: no sustained human-to-human transmission, with studies demonstrating a very low detection of virus or specific antibody in close contacts and healthcare workers of positive cases. 8 In both the first and the second waves, the majority of the patients hospitalised with H7N9 infection were older men and the case fatality was similar . Pre-existing medical conditions occurred in >60% of these cases. The prominent clinical features on admission were those of a severe influenza syndrome with fever, cough, fatigue and dyspnoea, while the most striking laboratory findings were marked lymphopenia and thrombocytopenia. Elevated cytokine levels have been observed in patients Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: This retrospective study was conducted from September 2009 to May 2010 at Hospital Sultanah Aminah Johor Bahru . HSAJB is a 989-bedded tertiary referral centre and the government designated hospital for H1N1 testing in Johor State, Malaysia. As the main General Hospital of Johor, its' patient population is reflective of the larger community in Malaysia. During our study period, which coincided with the peak of H1N1 pandemic activity, all patients regardless of whether they were hospitalized or not, who presented with an influenza-like illness were tested for H1N1.", "Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics\nPassage: Symptoms are common to each infection and manifest on a gradient. Generally, but far from always, influenza infection is more likely to result in a patient feeling so unwell as to take to their bed and have a fever, than RSV, an HRV, CoV or other common cold virus infection, during which daily life is usually less impacted. Title: Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012\u20132013: A PCR/Electrospray Ionization Mass Spectrometry Study", "Passage: Among the 117 episodes of single respiratory virus infections, arthralgia was more frequently observed in influenza A infections than in non-influenza infections vs. 46.6% , P \u00bc 0.033); for these 2 types of infections, the other examined symptoms, including sore throat, rhinorrhea, cough, purulent sputum, wheezing, dyspnea, and headache, were detected at similar frequencies. Title: Anxiety and Depression: Linkages with Viral Diseases", "Passage: the specific mechanisms can vary by viral illness. Mental conditions such as major depression can delay help-seeking or reduce the likelihood of detection of other health conditions including communicable diseases. 1 Depression and psychological stress have been shown to have a number of biological effects including reduced cell-mediated immunity and increased inflammatory processes. 3 A further issue is that some viral diseases can directly affect the brain and result in mood disorders or cognitive impairment. 1 Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: The clinical significance of viral/bacterial co-infections has long been a controversial topic. While severe bacterial pneumonia following influenza infection has been well described, associations are less clear among infections caused by viruses common in young children; secondary infections due to other viruses are less well understood and has been reviewed by others . Although assessing the overall contribution of bacteria to disease severity is complicated by the presence of many confounding factors in clinical studies, understanding the role of viral/bacterial co-infections in defining the outcome of paediatric ARI may potentially reveal novel treatment and prevention strategies, improving patient outcomes .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Individual human case studies report long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms. In one instance, a HCW shed viral RNA for 42 days in the absence of disease . It is an area of high priority to better understand whether such cases are able to infect others. Over three quarters of MERS cases shed viral RNA in their LRT specimens for at least 30 days, while only 30 % of contacts were still shedding RNA in their URT specimens . Title: Variation in RNA Virus Mutation Rates across Host Cells", "Passage: A 96-well plate containing 10 4 cells per well was inoculated with a limiting dilution of the viral stock such that approximately 10% of wells were infected. Plates were incubated at 37uC for 24 h, inspected under the microscope for cytopathic effects, and freezethawed to allow release of intracellular viruses. Viral RNA was purified from the supernatant of each of five positive wells and reverse-transcribed using AccuScript High Fidelity Reverse Transcripatse, and the cDNA was PCR-amplified using Phusion High Fidelity DNA polymerase and specific primers located in the P, G and L genes, as indicated. PCR products were cloned and Title: Viral RNA extraction for in-the-field analysis", "Passage: One millilitre of retroviral supernatant containing 6.5 \u00d7 10 5 functional virions was added into a 10 cm plate of 293T cells. As shown in Fig. 2 , not all cells are infected. Approximately, 2% cells were successfully transduced. The infected cells expressed GFP proteins 48 h after transduction, and showed strong green fluorescence. The GFP expression indicated the existence of retroviral virions in the supernatant, and most importantly allowed the estimation of functional virion numbers by titer. With these surrogate virions, it is possible to test the sensitivity and efficiency of the device quantitatively with minimal risk of viral Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Mix, 0.4 \u03bcl 50 \u00d7 ROX Reference Dye 1, 0.4 \u03bcl of each primer and 2 \u03bcl template RNA. Amplification was performed as follows: 50\u00b0C for 3 min, 95\u00b0C for 30 s followed by 40 cycles consisting of 95\u00b0C for 10 s, 60\u00b0C for 30 s, and a default melting curve step in an ABI 7500 machine.", "Title: Participant retention practices in longitudinal clinical research studies with high retention rates\nPassage: Of the 19 participating studies, 13 were prospective cohort studies, 5 were RCTs, and 1 was a quasiexperimental study . Included studies had diverse patient populations, including victims of intimate partner violence, persons living with human immunodeficiency virus and acquired immunodeficiency syndrome , survivors of critical illness and other serious illnesses. The target sample size for studies ranged from 255-10,000. Actual sample recruitment at the time of interview ranged from 205 for the Community Aging in Place -Advancing Better Living for Elders study with older adults aging in place to 2528 for the Alzheimer's Disease Anti-Inflammatory Prevention Trial . Though Title: Operationalising resilience in longitudinal studies: a systematic review of methodological approaches", "Passage: Included studies most commonly examined protective/ risk factors for resilience and were conducted in the USA with young-aged to middle-aged adults, that is, 20-40 years . Sample size ranged from 30 to 10 835 with an average of 758.69 and median of 233.5. Studies conducted a minimum of three waves of data collection and a maximum of seven , with an average follow-up period of 265.4 weeks . The source of adversity varied greatly; more studies included non-acute adversity, for example, cancer, than acute adversity, for example, disaster. The positive adaptations to these adverse events were less varied, generally demonstrated Title: The Trojan Chicken Study, Minnesota", "Passage: The study design was further limited in that we did not account for time after exposure when photographs were taken. Since participants could drop by any time of the day, the time after exposure and duration of exposure likely varied between participants. In both the feasibility and pilot studies, the return rate was low, and tracking down participants was difficult. If similar studies are conducted in the future, a reward system might be used to increase compliance. Title: Temporal changes in filtering-facepiece respirator fit", "Passage: Two hundred twenty-nine subjects were enrolled in the study and completed the first visit. Of these, 195 completed the second visit, and 134 completed all seven visits. Data were deleted for subjects who participated in Visit 1 but who did not participate in subsequent visits, thus, the analyses in this study were conducted on the remaining 195 subjects. Subjects were characterized by face size in the NIOSH bivariate panel . The majority of the subjects had a face length greater than 110 mm and less than 130 mm. This face size distribution among the 195 subjects used in this study", "Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: The time series data of 2019-nCoV cases in mainland China were initially released by the Wuhan Municipal Health Commission from 10 to 20 January 2020 , and later by the National Health Commission of China after 21 January 2020 . The case time series data in December 2019 were obtained from a published study . All cases were laboratory confirmed following the case definition by the national health commission of China . We chose the data up to 24 January 2020 instead of to the present study completion date. Given the lag between timings of case confirmation and news release Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: For the simulated daily number of cases , see Figure 1d , we found that \u03b5 i matched the observed daily number after 17 January 2020, but was significantly larger than the observations from 1 to 17 January 2020. This finding implied that under-reporting was likely to have occurred in the first half of January 2020. We estimated that the reporting rate after 17 January 2020 increased 21-fold compared to the situation from 1 to 17 January 2020 on average. One of the possible reasons was that the official diagnostic protocol was released by WHO on 17 January 2020 , Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: . Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation. Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: and the diagnosis and reporting efforts of 2019-nCoV infections probably increased. Thereafter, the daily number of newly reported cases started increasing rapidly after 17 January 2020, see Figure 1d . We conducted additional sensitivity analysis by varying the starting date of the under-reporting time window, e.g., 1 January 2020 in the main results, from 2 December 2019 to 3 January 2020, and we report our estimates largely hold. The exact value of the reporting rate was difficult to determine due to lack of serological surveillance data. The reporting rate can be determined if serological surveillance data are available for a", "Title: Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog\nPassage: and 4. The cloned CEACAM25 splice variants also code for proteins with only one N domain followed by a transmembrane domain. Three out of four clones encode cytoplasmic domains which contain the predicted ITAM motif . In one clone, the absence of the 53 nucleotide cytoplasmic domain exon 1 leads to a frame shift and the usage of an alternative stop codon located in cytoplasmic domain exon3 . Using supposedly CEACAM28specific primers, two products were amplified which differ in their length by 276 bp. Cloning and sequencing revealed that the CEACAM28 gene codes for a protein with one N domain, Title: Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog", "Passage: dog CEACAM23-CEACAM25, CEACAM28 and CEACAM29 molecules. Subsequently, we screened about 2,000 bp of nucleotide sequence downstream of the predicted canine transmembrane domain exons for the presence of the short cytoplasmic exons. Indeed, small cytoplasmic domain exons similar to the ones found in human CEACAM3 and CEACAM4 could be identified, which encode ITAM motifs close to the C-terminal end . Although homologous cytoplasmic domain exons 1-3 are present in CEACAM29 the loss of the splice donor site in the cytoplasmic domain exon 3 leads to read through into the adjacent intron and truncation by a stop codon following after five codons. Title: CEACAM1 in Liver Injury, Metabolic and Immune Regulation", "Passage: CEACAM1L, 3L and 4L as well as CEACAM18-21 possess a transmembrane anchor with a cytoplasmic tail , whereas CEACAM5-8 are GPI-linked. Schematic representation of the 12 CEACAM1 protein isoforms as products of alternative splicing of the human CEACAM1 gene: The most prominent and best-studied CEACAM1 isoforms are highlighted in a blue box. They either comprise a long or a short cytoplasmic tail and four or three extracellular immunoglobulin-like domains . Amongst the 12 isoforms, further 4-domain variants are found with a modified short cytoplasmic tail or a soluble isoform . Additional soluble isoforms include CEACAM1-3 and CEACAM1-C2. The membrane-bound CEACAM1-1L Title: Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1", "Passage: Eleven CEACAM1 splice variants have been reported in humans 20 . CEACAM1 isoforms can differ in the number of immunoglobulin-like domains present, in the presence or absence of a transmembrane domain and/or the length of their cytoplasmic tail . The full-length human CEACAM1 protein consists of four extracellular domains domain and three immunoglobulin constant region 2-like domains), a transmembrane domain, and a long cytoplasmic tail. The long cytoplasmic tail contains two immunoreceptor tyrosine-based inhibitory motifs that are absent in the short form 20 . The most common isoforms expressed by human immune cells are CEACAM1-4L and CEACAM1-3L 21 . CEACAM1", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Tuberculosis care for pregnant women: a systematic review\nPassage: generalise the conclusions.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: The mouse-adapted SARS virus was generated by serial passage of an infectious wildtype SARS CoV clone in the respiratory tract of BALB/c mice. After 15 passages in mice, the SARS-CoV gained elevated replication and lung pathogenesis in aged mice , due to six coding genetic mutations associated with mouse adaptation. It is likely that MA15 is highly attenuated to replicate in human cells or patients due to the mouse adaptation. Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Due to the elevated pathogenic activity of the SHC014-MA15 chimeric virus relative to MA15 chimeric virus with the original human SARS S gene in mice, such experiments with SL-SHC014-MA15 chimeric virus were later restricted as gain of function studies under the US government-mandated pause policy . The current COVID-2019 epidemic has restarted the debate over the risks of constructing such viruses that could have pandemic potential, irrespective of the finding that these bat CoVs already exist in nature. Regardless, upon careful phylogenetic analyses by multiple international groups , the SARS-CoV-2 is undoubtedly distinct from SL-SHC014-MA15, with >6,000 nucleotide differences across Title: The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus", "Passage: Influenza virus A/Anhui/1/2013 was isolated from the third case of laboratory-confirmed human A virus, with Q226L mutation in the receptor binding domain of HA protein. The patient was a 35-year-old woman who lived in Anhui Province of China. She had visited a chicken market one week before the onset of symptoms. ARDS, septic shock, and acute renal damage developed on day 6 post the onset of illness. The patient was treated with oseltamivir , but eventually died on 19 days after the onset of illness . A throat swab was collected from the patient and propagated in the allantoic sac Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: same contact sites as the human ACE2 gene for interacting with SARS CoV , it was proposed that an intermediate host may not be necessary and that some bat SL-CoVs may be able to directly infect human hosts. To directly address this possibility, the exact S gene from bat coronavirus SL-SHC014 was synthesized and used to generate a chimeric virus in the mouse adapted MA15 SARS-CoV backbone. The resultant SL-SHC014-MA15 virus could indeed efficiently use human ACE2 and replicate in primary human airway cells to similar titres as epidemic strains of SARS-CoV. While SL-SHC014-MA15 can replicate efficiently in young and", "Title: Virus\u2013Host Coevolution with a Focus on Animal and Human DNA Viruses\nPassage: greatly, they appeared to form a monophyletic group with a common ancestor, based on a subset of about 30 conserved genes . For instance, iridoviral homologues of ATPase, the A1L/VLTF2 transcription factor, the major capsid protein and the DNA polymerase proteins show considerable sequence similarity with asfar-, asco-, mimi-, pycodna-and poxvirus counterparts . Title: Virus\u2013Host Coevolution with a Focus on Animal and Human DNA Viruses", "Passage: adenoviruses and some archaeal viruses all have a double jellyroll fold structure , or there are structural homologies in the RNA-and DNA-dependent polymerases too . There are fold superfamilies containing both viral and cellular proteins , but there are also numerous examples without cellular homologues found in phylogenetically very diverse viruses: e.g. viral RNA-dependent RNA polymerases are not homologous to their cellular counterparts . According to the most parsimonious assumption, these proteins have a common origin in the primordial virus world, and phylogenetic tree reconstructions of these fold superfamilies confirm this as well . Title: Viral Proteins Acquired from a Host Converge to Simplified Domain Architectures", "Passage: For few instances, a support exists for viruses that hijacked sequences from the host. Among Class I viruses the shared functions include interlukin-10 , beta-1,6-Nacetylglucosaminyltransferase and Ubiquitin. The b1,6GnT and IL-10 are found exclusively in metazoa and the multicellular eukaryotic branch. The key features and the functional amino acids are conserved in the viral and the corresponding mammalian proteins . Indeed, in human cells lacking b1,6GnT gene, the Bovine herpesvirus 4 sequence fully recovered the missing enzymatic activity . Title: Virus\u2013Host Coevolution with a Focus on Animal and Human DNA Viruses", "Passage: Shifting the perspective to branch #2 families: we can see that using a concatenated set of 9 genes common to these, a close relationship has been confirmed, suggesting that ascoviruses emerged recently and share a common ancestor with invertebrate iridoviruses . However, the replication strategies and morphologies are markedly different in these two virus groups replicating in invertebrate hosts . The evolutionary steps leading to these significant alterations still remain obscure.", "Title: Stochastic modelling of infectious diseases for heterogeneous populations\nPassage: There are some limitations in our proposed stochastic model. First, it does not consider the epidemic network topology. However, how to infer such networks is another challenging task. To the best of our knowledge, the best way to do so is to use the contact data among some infected patients to verify the results, but such data are not always available and can be difficult to collect due to many issues . This issue may be addressed by using other types of data, such as daily commute data extracted from social networks. Second, our proposed model achieves a prediction accuracy Title: A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern", "Passage: Our systematic review did not delve deeply into modeling approaches, but did identify a preponderance of deterministic as opposed to stochastic models. Both categories of models have pros and cons and their use is often informed by the specific question being addressed, in addition to data availability . Deterministic models may generally be easier to produce, but they may have limitations for intrinsically stochastic processes like epidemics, such as underestimating uncertainty, although deterministic models can also be implemented to estimate uncertainty . Uncertainty is particularly important in this context where uncertainties are generated by the epidemic itself, data collection, and Title: Fitting dynamic models to epidemic outbreaks with quantified uncertainty: A primer for parameter uncertainty, identifiability, and forecasts", "Passage: Mathematical models provide a quantitative framework with which scientists can assess hypotheses on the potential underlying mechanisms that explain patterns in the observed data at different spatial and temporal scales. Models vary in their complexity in terms of the number of variables and parameters that characterize the dynamic states of the system, in their spatial and temporal resolution , and in their design . While agent-based models, formulated in terms of characteristics and interactions among individual agents, have become increasingly used to model detailed processes often occurring at multiple scales , models based on systems of ordinary differential equations are Title: Lessons from a decade of individual-based models for infectious disease transmission: a systematic review (2006-2015)", "Passage: Time horizons and modeling step sizes in the full-text articles were diverse and are subject to disease characteristics and research objectives. There is no standard approach on the number of stochastic realizations, which seems model specific and requires sensitivity analysis. Models focusing on key factors of between-host dynamics in large populations with homogeneous mixing will not produce much stochastic variability and require fewer realizations compared to simulations combining complex social mixing clusters, adaptive behavior, withinhost dynamics and medical backgrounds . One of the most frequent criticisms of IBMs is that \"they can be calibrated to say anything\" . This is", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Very few empirical studies have attempted to determine whether urbanization is related to EID outbreaks or whether urbanization is associated primarily with other factors related to EID outbreaks. One immediate problem researchers face is defining what is rural, urban, and transitional . Some studies have used official administrative definitions of urban and rural areas, but this approach is limited in its bluntness . Other studies prioritized human population density as a satisfactory surrogate , but this approach ignores the important fact that density is not a risk factor if it is accompanied by sufficient infrastructure to handle the population. Spencer Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: Very few empirical studies have attempted to determine whether urbanization is related to EID outbreaks or whether urbanization is associated primarily with other factors related to EID outbreaks. One immediate problem researchers face is defining what is rural, urban, and transitional . Some studies have used official administrative definitions of urban and rural areas, but this approach is limited in its bluntness . Other studies prioritized human population density as a satisfactory surrogate , but this approach ignores the important fact that density is not a risk factor if it is accompanied by sufficient infrastructure to handle the population. Spencer Title: Factors Associated with Increased Risk Perception of Pandemic Influenza in Australia", "Passage: economic consequences, including the possibility of influenza transmission from animals to human. However, though individuals living in rural areas believed that pandemic influenza was more likely to occur than individuals living in urban areas, they did not display more concern for self and family should a pandemic influenza occur. This is not unexpected given that the influenza virus is more easily transmitted from person to person in crowded environments, and that rural environments are typically not densely populated. It might be expected however that individuals living in urban environments may be more concerned for self and family in the case Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: Only one other study has explicitly examined urbanicity in the context of HPAI H5N1. Loth et al. found peri-urban areas in Indonesia were significantly associated with HPAI H5N1 cases, even based on multivariate models. Our study, however, attempted both to associate HPAI H5N1 with degree of urbanicity and to determine the features of peri-urban areas that place them at risk. When those features are included in multivariate models, the role of the urbanization variable per se diminishes. We found in the main river deltas in Viet Nam , urbanization had no significant association with HPAI H5N1. This may be due", "Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris\nPassage: secretion to display for full length IgGs, they suffer drawbacks of their own, including the need for modifying the protein sequence to allow surface binding in particular cases. Moreover, re-capture following secretion introduces the risk of \"crosstalk\" between clones that could lead to the loss of the required genotype-to-phenotype relationship that is critical for efficient lead-cell isolation. Without a strong genotype-to-phenotype relationship built into the display system the issue of \"cross talk\" among clones in the same culture must be addressed through tedious experimental modifications . Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: We have presented the development of a novel dual-mode display and secretion technology in Glyco-engineered Pichia pastoris, and demonstrated the utility of this method in selecting mAb leads with variable affinities and high productivity. The combination of display and secretion in the same clone enables the continuity and fidelity of the antibody discovery process and could lead to shortened maturation cycle and desirable lead developability. Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: Surface display boasts the ability to link genotype to phenotype. In the classical antibody display paradigms, sorted clones are isolated and their genotypes are subcloned into new production hosts. This cloning step involves screening multiple clones to isolate ones with defined properties. The anchored Fc system side-steps the need for these additional steps by combining selection of antibody affinity and production host in a single experiment. Libraries can be generated and displayed in the cell line of choice, such as Glyco-engineered Pichia pastoris. Selected clones can be fermented directly in small or large scale vessels to generate material for in Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: Flow cytometric analysis and cell sorting were performed on a FACSAria cell sorter with blue and red lasers equipped with FACSDiva software. The procedure was performed according to Lin et al. . Gating in a dot plot of FSC vs. SSC was routinely applied to exclude cell debris and to include a population of single cells with similar size for analysis and sorting. For each sort, the 1% of cells with the brightest signal were gated and 5000-10,000 total cells were collected. Flow cytometry data were analyzed with software FlowJo v 7.1.2 .", "Title: Personal genomes, quantitative dynamic omics and personalized medicine\nPassage: As technology improves we expect to see advancements in each omics implementation discussed above. In terms of sequencing, continual improvements in depth and read length will allow unambiguous precise sequence mapping and additionally the querying of lower gene expression, coupled to higher accuracy in variant calling. With sequencing times becoming faster , and hardware more compact, eventually such technology will be available in the clinic, enabling the incorporation of all genomic, transcriptomic, microbiomic and autoantibodyomic profiling as parts of regular medical examinations. Correspondingly, mass spectrometry improvements will improve mass accuracy, and higher sensitivity, allowing increases in the number of proteins Title: Personal genomes, quantitative dynamic omics and personalized medicine", "Passage: Technologies . The technological developments and competition resulted in a drastic and continuing drop in sequencing cost, processing times and exponential increases in number of reads produced. Title: Personal genomes, quantitative dynamic omics and personalized medicine", "Passage: The HGP relied on technology using Sanger-based capillary sequencing with an estimated production of 115k base pairs per day . The NHGRI spurred progress by encouragement through the $1000 genome program , leading to the industry development of multiple massively parallel sequencing platforms ; Life Technologies SOLiD ; Illumina ; Complete Genomics based on DNA nanoball sequencing ; Helicos Biosciences ; and recently single molecule real-time technology by Pacific Biosciences). These next generation sequencing platforms are now being supplemented but what has been termed as thirdgeneration sequencing, , including such nanopore technologies as announced early in 2012 by Oxford Nanopore Title: Personal genomes, quantitative dynamic omics and personalized medicine", "Passage: The development of RNA sequencing brought higher coverage, better precision and quantitation, and higher resolution and sensitivity, bringing RNA-Seq technology and transcriptomics on par with genomic sequencing . RNA-Seq considers reads that correspond to millions of transcriptomic fragments that are mapped to the reference genome, to provide information on transcripts that may not be in the existing genomic annotation, allowing the search for novel transcripts, and even identification of SNPs and other variants, while showing remarkable reproducibility . Transcriptome profiling has included looking at cancers , including breast cancer , gastrointestinal tumors and prostate cancer .", "Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data\nPassage: further divided in a recursive manner until the subgroups reach a minimum size or until no further improvement can be made. The resulting tree may overfit the training data. To avoid this, crossvalidation was used in the second stage by pruning the tree. We fixed the maximum depth of the tree, i.e., the maximum number of branchings from stem to leaf, to be 20. The final models were tested on the test data and performance statistics are found. We repeated modelbuilding 10 times for each test and summarized the statistics. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: for predicting laboratory results are unclear. However, while CART is both a top performer and overcomes GLM's problem with missing values, it is also more computationally intensive and potentially less sensitive to simple algebraic relationships among features . Therefore we chose GLM as a well-understood approach with strong performance and excellent speed, and CART as the bestperforming complementary approach for purposes of comparison. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: Other methods, such as classification and regression trees and artificial neural networks , have also been applied. Most of these studies were limited in scope to predicting risk of a particular diagnosis. Harper compared four classification techniques on four different datasets and concluded that there was no obvious best choice for their data; while CART performed best, regression was fastest and nearly as good. Similar comparative studies on coronary artery disease and Alzheimer disease indicated that newer algorithms such as ANN and random forests have little advantage over simpler, more traditional approaches. Also, the utility and limitations of these approaches Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: Of note, there was no guarantee that any feature would be significantly correlated or that there would be enough instances of the test appearing with all features of even the reduced featureset for glm to produce a model. When feature elimination resulted in no significant features or too few instances, no model was constructed. We scored models using PPV, NPV, and ROC AUC.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: AAV vector systems have a number of engaging properties. The wild type viruses are non-pathogenic and replication incompetent in humans and the recombinant AAV vector systems are even further attenuated . As members of the parvovirus family, AAVs are small non-enveloped viruses that are stable and amenable to long-term storage without a cold chain. While there is limited preexisting immunity, availability of non-human strains as vaccine candidates eliminates these concerns. Modifications to the vector have increased immunogenicity, as well . Title: Viral vector-based influenza vaccines", "Passage: Adeno-associated virus is a parvovirus that is replication-deficient in humans. Like adenovirus, AAV has a broad cell, tissue and host tropism and therefore is a potential good vector vaccine. 218 However, drawbacks of using AAV include: limited capacity for transgenes, presence of pre-existing immunity in humans and the technical challenge of producing high titer stocks. Initially, AAV was not explored as a vaccine vector as it was considered to be poorly immunogenic, however vaccination studies in mice showed that AAV-2 expressing an HSV-2 glycoprotein was immunogenic and a potent inducer of Tcell and antibody responses, 219 and currently modifications are Title: Viral vector-based influenza vaccines", "Passage: being made to AAV to increase immunogenicity. 220 A limited number of studies evaluating AAV as a vector for influenza vaccination has been performed . Initially, an AAV expressing the HA gene or NP gene was shown to be protective in mice. 221, 222 A more recent study tested AAV vaccines expressing the HA, NP or M1 genes of H1N1pdm09 in mice. Whereas AAV-HA afforded full protection from H1N1pdm09 infection, AAV-NP protected mice partially and AAV-M1 did not afford protection. Simultaneous vaccination with all 3 constructs afforded protection from homologous challenge infection. 223 Recently, in an alternative vaccination approach, AAV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adeno-associated viruses were first explored as gene therapy vectors. Like rAd vectors, rAAV have broad tropism infecting a variety of hosts, tissues, and proliferating and non-proliferating cell types . AAVs had been generally not considered as vaccine vectors because they were widely considered to be poorly immunogenic. A seminal study using AAV-2 to express a HSV-2 glycoprotein showed this virus vaccine vector effectively induced potent CD8 + T cell and serum antibody responses, thereby opening the door to other rAAV vaccine-associated studies .", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: On this occasion information sharing seems to have been rapid and effective . The WHO was notified of the original clustering within days and the full genomic sequence of the new virus was published less than 2 weeks after the cluster was first detected. The WHO has expressed its satisfaction with the actions of the Chinese authorities in sharing information with the WHO. Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: By 26 January also, almost 50 million people in Wuhan and neighbouring cities had effectively been placed in quarantine while the WHO had determined that the event should not yet be declared as a Public Health Emergency of International Concern and had recommended no specific travel restrictions. The WHO have emphasised the importance of exit screening at ports in countries showing transmission of the novel coronavirus and have provided guidance for countries implementing entry screening at airports while acknowledging that evidence for the effectiveness of entry screening is equivocal. Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: Text: On 29 December 2019 clinicians in a hospital in Wuhan City, China noticed a clustering of cases of unusual pneumonia with an apparent link to a market that sells live fish, poultry and animals to the public. This event was reported to the World Health Organisation on 31 December . Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine", "Title: A method of processing nasopharyngeal swabs to enable multiple testing\nPassage: A total of 25 samples were sequenced with an average of 63 million paired-reads per sample. All 25 RNA samples were within the expected purity ratio of \u22651.8. The mean RNA yield was 772.3 ng. All RNA samples used in this study had an RNA Integrity number of \u22656.0. On average 93% of reads had a quality score of 30 of higher. Samples were mapped to the Hg19 Human genome build with an average of 97% mapping rate . Title: A method of processing nasopharyngeal swabs to enable multiple testing", "Passage: We processed 163 samples for 16S rRNA gene amplicon sequencing. We were able to recover on average >16,000 sequences per sample, accounting for a total of 2,646 OTUs. When rarefied to10,000 sequences per sample in order to capture most of the samples and normalize depth of coverage, rarefaction curves indicated that the NP swabs and sequencing depth adequately sampled microbial species richness . As expected, when more sequences were analyzed per sample, the lines start to plateau . This indicates that even though more sequences were analyzed, few new species were detected. Furthermore, no significant difference was observed in species Title: Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti", "Passage: over five weeks for Survey 1; 257 plates over nine weeks for Survey 2; and 59 plates over four weeks for Survey 3. Together these represent 32,758 participant samples processed over an eighteen-week period. After removal of median fluorescence intensity data across all analytes for samples with missing or high responses to the generic glutathione-S-transferase , 5,898 samples passed QC in Survey 1 ; 21,234 samples in Survey 2 ; and 4,967 samples in Survey 3 . Removal of single analytes' datapoints due to low bead counts accounted for additional minor loss of data . Following these QC checks, there Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: We approached 31 households to take part in the pilot study and 30 agreed . These represented 15 ill adults and 15 ill children . All households reported in the follow-up call that they had obtained the sample, and we received 29 samples by mail, and one specimen brought directly to the laboratory). Of those who mailed the specimen, most reported mailing it within 1 day; all reported mailing it within 2 days. The median time between the kit being dropped off and arrival to the laboratory was 8 days .", "Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016\nPassage: 68.8 % males: mean age was 53.2 years , and 31.2 % females: mean age was 53.2 years , where the youngest patient reported was 10 month and the oldest patient reported was 109 year old. Comorbidities were reported in 46.9 %: mean age was 60.1 and 71.8 % male and 28.2 % female. Healthcare workers were reported to be 15.6 %, mean age was 38.6 and 53.3 % male, 46.7 % female and 19.7 % of them had comorbidities. 12.1 % reported with history of camel contact; mean age was 56.7 and 91.7 % male, 8.3 % female and Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response\nPassage: 0.132 in people aged under 30 years, and 0.134 and 0.122 for those aged 30 years and over. Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Patients' sex-ratio was 0.63 and mean age was 28.4 years . Ten percent had less than 5 years, 24% 5-15 years, 63% 15-65 years and only 3% were 65 and older. Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers\nPassage: The study took place from August 24, 2009, through December 16, 2009, largely before release of the pandemic infl uenza vaccine, and no participant was vaccinated during the study. Table 1 shows the number of patients who had confi rmed pandemic infl uenza infection and were treated in each of the hospitals. Characteristics of study participants are shown in Table 2 . The median participant age was 38 years ; 27% were <30 years of age, 20% were 30-39 years of age, 25% were 40-49 years of age, and 20% were >50 years of age. Figure 2 shows the reverse", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Tuberculosis care for pregnant women: a systematic review\nPassage: generalise the conclusions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: A Simulation Optimization Approach to Epidemic Forecasting\nPassage: amplitude and durations of three pre-2006 influenza pandemic events in England and Wales. They used regression techniques to fit a time-series disease incidence curve obtained from a traditional differential equation epidemiology model to the mortality and influenza-like illness data for the three pandemics. This technique required estimation of nine parameters, including the reproduction number. The model also assumed knowledge of the natural history of the disease from detailed epidemiological studies in the early stages of the pandemic. Title: On epidemic modeling in real time: An application to the 2009 Novel A (H1N1) influenza outbreak in Canada", "Passage: The accuracy of any modeling is highly dependent on the epidemiological characteristics of the outbreak considered, and most epidemic curves exhibit multiple turning points during the early stage of an outbreak. While these may be due to stochastic variations in disease spread, and changes in either surveillance methods or case definitions, turning points may also represent time points where epidemics transition from exponential growth processes to processes that have declining rates of growth, and thus may identify effects of disease control programs, peaks of seasonal waves of infection, or natural slowing of growth due to infection of a critical fraction Title: On epidemic modeling in real time: An application to the 2009 Novel A (H1N1) influenza outbreak in Canada", "Passage: Data were accessed at different time points during the course of the \"spring wave \" of the epidemic in May-July of 2009, whenever a new dataset is made available online by the PHAC. By sequentially considering successive S-shaped segments of the epidemic curve, we estimate the maximum case number and locate turning points, thus generating estimates for cumulative case numbers during each phase of the outbreak. The PHAC cumulative case data is then fitted to the cumulative case function C in the Richards model with the initial time t 0 = 0 being the date when the first laboratory confirmed Title: On epidemic modeling in real time: An application to the 2009 Novel A (H1N1) influenza outbreak in Canada", "Passage: For epidemics with two or more phases, a variation of the S-shaped Richards model has been proposed . This multi-staged Richards model distinguishes between two types of turning points: the initial S curve which signifies the first turning point that ends initial exponential growth; and a second type of turning point in the epidemic curve where the growth rate of the number of cumulative cases begins to increase again, signifying the beginning of the next epidemic phase. This variant of Richards model provides a systematic method of determining whether an outbreak is single-or multi-phase in nature, and can be used", "Title: Poultry farms as a source of avian influenza A (H7N9) virus reassortment and human infection\nPassage: The continued introduction of different species of poultry and the mixed breeding model may have contributed to the diversified genotypes generated by co-circulation of the H7N9 and H9N2 viruses on the patient's farm. Nearly 1,000 birds of five species including chickens, guinea fowl, black-bone Silkie chickens, turkeys and geese were involved in this process. Chickens were the most prevalent poultry species on the patient's farm. Previous studies have suggested that H7N9 and H9N2 predominately circulate in chickens 27, 32 , indicating that the genesis of the diversified genotypes most likely occurred in chickens. However, the mixed breeding model may also Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: has been proven that farm duck breeds can shed the H5N1 virus with minimal clinical signs , our results suggest that farm ducks may also have played the role of silent carriers during the second wave of the epidemic, contributing to the spread of the disease. In addition, an increased risk in duck flocks was shown for subdistricts with a high density of broiler and layer chickens . In Thailand, broiler and layer chicken production range from large-scale industrial farms to small, family-run operations . The latter refer to small or medium-scale businesses with links to several middlemen or companies Title: Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds", "Passage: crane-05 while there were no appreciable differences in the virus shedding in the cloaca. Beyond such constrains, we demonstrated that one strain of H5N1 HPAIV, pigeon-04, induced an extended MDT in Thai indigenous chickens. Although we could not identify the host factor associated with increased resistance to HPAIV, the genetic diversity of Thai indigenous chickens may be useful tool for determining the host defense mechanism against HPAIV through extensive genetic analyses. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Both the GLMM and BRT models indicated that the diversity of chicken flock-size had a strong association with HPAI H5N1 for both waves at the national level. This was generally found to be true at the delta levels with some exceptions. The diversity of duck and goose flock size was also significantly associated with HPAI H5N1 in all places, but the associations were much stronger in Wave 2 than in Wave 1.", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: 0.6 or 0.9 in Middle East countries . However, MERS had a high transmissibility in the outbreak in the Republic of Korea with the R 0 of 2.5-7.2 . Therefore, the transmissibility of SARS-CoV-2 might be higher than MERS in the Middle East countries, similar to SARS, but lower than MERS transmitted in the Republic of Korea. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: Researches showed that the R 0 of severe acute respiratory syndrome was about 2.7-3.4 or 2-4 in Hong Kong, China . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 . The transmissibility of the Middle East respiratory syndrome is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 , with the inter-human transmissibility of the disease was about Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: By calculating the published data, our model showed that the transmissibility of SARS-CoV-2 might be higher than MERS in the Middle East countries, similar to SARS, but lower than MERS in the Republic of Korea. Since the objective of this study was to provide a mathematical model for calculating the transmissibility of SARS-CoV-2, the R 0 was estimated based on limited data which published in a literature. More data were needed to estimate the transmissibility accurately. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: In this study, we used the R 0 to assess the transmissibility of the SARS-CoV-2. Commonly, R 0 was defined as the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population . If R 0 > 1, the outbreak will occur. If R 0 < 1, the outbreak will toward an end. In this study, R 0 was deduced from the RP model by the next generation matrix approach . The multiple of the transmissibility of A P to that of I P .", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: in the past before HIV/AIDS arose. No side effect for humans lacking this gene has been described . Title: The origins of the great pandemic\nPassage: of Western Hemisphere and, probably, North American origin and that the pandemic virus's HA gene was likely circulating in the human population for many years prior to 1918 . These studies suggest, moreover, that the virus reassortment event giving rise to the pandemic probably occurred in or around 1915-since the common ancestor of human and swine H1N1 genomic segments, and in some cases the common ancestor of human, swine, and avian segments, can be dated to that time window-long before the Kansas cases. Therefore, we should remain cautious in the face of incomplete knowledge. In a nutshell, the chance that Title: Virus\u2013Host Coevolution with a Focus on Animal and Human DNA Viruses", "Passage: What can be the origin of an obligatory cellular parasite? Three concurring hypotheses describe the origin of viruses: the primordial virus world or the virus first hypothesis claims that the ancestors of viruses existed already in the pre-cellular world; the escaped genes theory describes viruses as mobile genetic elements, which became independent of their host cells; whereas according to the cellular regression theory, viruses are regressed intracellular parasites . Title: Virus\u2013Host Coevolution with a Focus on Animal and Human DNA Viruses", "Passage: According to the primordial virus world hypothesis, in the primordial soup multiple pre-cellular and pre-viral Urorganisms competed with each other. The last universal common ancestor-the first cellular life form-emerged from these primordial replicators, and at least a fraction of current viruses might originate from the remaining ones . Ancient viruses might have even contributed to the formation of the last universal common ancestor of all living organisms.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: . Furthermore, the humanized mouse model that possess human immune cells may also serves to unravel the immune profile of a viral infection in healthy and diseased condition . For milder viruses, controlled in vivo human infections can be performed for the best mode of verification of the associations of the virus with the proposed mechanism of viral induced acute exacerbations . With the advent of suitable diseased models, the verification of the mechanisms will then provide the necessary continuation of improving the management of viral induced acute exacerbations. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection can exacerbate the disease. The review will serve to provide further understanding of viral induced exacerbation to identify potential pathways and pathogenesis mechanisms that may be targeted as supplementary care for management and prevention of exacerbation. Such an approach may be clinically significant due to the current scarcity of antiviral drugs for the management of viral-induced exacerbations. This will improve the quality of life of patients with chronic airway inflammatory diseases.", "Title: Estimating the number of infections and the impact of non-\nPassage: and the time-varying reproduction number. Finally, the time-varying reproduction number is a Title: Estimating the number of infections and the impact of non-\nPassage: The functional form for the time-Varying reproduction number was chosen to be as simple as possible Title: Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic", "Passage: The model, in the formalism chosen here, predicts the changing incidence rate I as a function of calendar time t in terms of the transmissibility, denoted b , an arbitrary function of calendar time t and time since infection t. b typically reflects pathogen load, or perhaps more precisely pathogen shedding. It is commonly a single peaked function reflecting pathogen growth followed by immune suppression, or host death, but can be more exotic such as the double peaked profile associated with early and late transmission of HIV , or the repeated peaks of malaria . b also reflects the effective Title: Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases", "Passage: reproduction number) is a function of time; the last expression is exact if S/N is constant in the period . This simplifying assumption is generally excellent for emerging infectious diseases, which result in few cases within a much larger population. Generally the validity of the assumption can be assessed through consideration, from , of its evolution equation", "Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: Although I only have a limited number of concrete suggestions and do not think the general criticism above is necessarily fair, I would encourage the authors to think more creatively about what further information can be harvested from the model -perhaps biological parameters that are entirely inaccessible using other approaches and what additional analyses can be done to confirm that the inferences are biologically meaningful. In any case, tightening up the logic of the real data analysis should be helpful to readers like me. Title: Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation", "Passage: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Title: An examination of the factorial and convergent validity of four measures of conspiracist ideation, with recommendations for researchers\nPassage: fixed at the indicated value . Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: related profiles of selection. We believe that these lines of evidence add credibility to our findings, which, we hope, will stimulate additional experimental analysis of the potentially novel associations described in the manuscript.", "Title: DNA Vaccines\u2014How Far From Clinical Use?\nPassage: Compared to conventional protein/peptide-based vaccines intended to induce antigen-specific adaptive immune responses, DNA vaccines are more stable, cost-efficient, easy to manufacture and safe in handling . DNA vaccines are being investigated for various applications including therapy of cancer , allergies , autoimmune and infectious diseases . In the US, at the moment over 500 clinical trials that focus on DNA vaccination are registered, targeting especially viral infections and cancer , while bacterial infections and autoimmune diseases are less of a topic. The high number of DNA-vaccines tested in clinical trials emphasizes their important role for future medical approaches. This review Title: DNA Vaccines against Protozoan Parasites: Advances and Challenges", "Passage: Also, a few studies provided interesting comparisons of the same antigens administered as recombinant protein or DNA vaccines and showed that the latter were overall more effective than their recombinant protein counterparts. Indeed, DNA vaccines were able to induce a stronger Th1 bias in the immune response, a longer-lasting immunity, and/or a better protection against disease progression . While most of these studies have used a rather artificial infectious challenge based on the injection via nonnatural routes of high parasite doses, an experimental system criticized by some authors, the superior efficacy of DNA vaccines was also observed using a low-dose Title: Polyvalent DNA Vaccines Expressing HA Antigens of H5N1 Influenza Viruses with an Optimized Leader Sequence Elicit Cross-Protective Antibody Responses", "Passage: recent studies , a DNA prime-inactivated vaccine boost is highly effective in eliciting higher protective immune responses than using either DNA or inactivated flu vaccine alone. Therefore, it may be possible to use DNA vaccines as the first dose of immunization that can be given either long before the pandemic or shortly after the outbreak, to reduce the burden on the production of inactivated vaccines at the time of the outbreak. Furthermore, DNA vaccines can be stockpiled for a long period of time, which makes this method even more attractive. Title: DNA Vaccines: Developing New Strategies against Cancer\nPassage: DNA vaccines offer the opportunity to incorporate additional genes encoding molecules aimed at overcoming the weak immunogenicity of tumor antigens and the patients' tolerized immune repertoire.", "Title: Estimating the number of infections and the impact of non-\nPassage: United Kingdom 2.7% Title: Estimating the number of infections and the impact of non-\nPassage: Table l: Posterior model estimates of percentage of total population infected as of 28th March 2020. Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: 57. UK Government. PM address to the nation on coronavirus: 23 March 2020. UK Government", "Title: Modeling the impact of quarantine during an outbreak of Ebola virus disease\nPassage: modeling studies for the 2014 EVD outbreaks ). Title: The Model Repository of the Models of Infectious Disease Agent Study\nPassage: Typical model examples include the analysis and optimization of tools and workplace layout, and designing sports equipment and hand tools for maximum efficiency. A unique software system called the AnyBody Modeling System was developed to conduct necessary research into causes and treatments of musculo-skeletal injuries. Title: Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus", "Passage: In the disease transmission model, latent ) and infectious ) travelers arrived from 44 foreign countries by transport k-th and were assigned to compartments E and I, respectively. Because the screening sensitivity at the border points of entry was limited, a proportion of infectious cases were imported to Hong Kong, an approach not considered in other global patch models . The number of cases imported to the local city was also assumed to be binomially distributed, with a probability equal to the chance of travel via the specified transport mode. Title: Modeling the impact of quarantine during an outbreak of Ebola virus disease\nPassage: To show that all solutions of the model The result below follows from the above analyses.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The NYVAC vector is a highly attenuated vaccinia virus strain. NYVAC is replication-restricted; however, it grows in chick embryo fibroblasts and Vero cells enabling vaccine-scale production. In non-permissive cells, critical late structural proteins are not produced stopping replication at the immature virion stage . NYVAC is very attenuated and considered safe for use in humans of all ages; however, it predominantly induces a CD4 + T cell response which is different compared to MVA . Both MVA and NYVAC provoke robust humoral responses, and can be delivered mucosally to induce mucosal antibody responses . There has been only limited exploration Title: Virus-Vectored Influenza Virus Vaccines", "Passage: . Intriguingly, NYVAC may have an advantage for use as an influenza vaccine vector, because immunization with this vector induces weaker vaccine-specific immune responses compared to other poxvirus vaccines, a feature that may address the concerns surrounding preexisting immunity . Title: Virus-Vectored Influenza Virus Vaccines\nPassage: of NYVAC as a vaccine vector for influenza virus; however, a vaccine expressing the HA from A/chicken/Indonesia/7/2003 was shown to induce potent neutralizing antibody responses and protect against challenge in swine . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2 . Poxviruses are also studied extensively as candidate vectors for human use, among which attenuated derivatives of vaccinia virus and New York attenuated vaccinia virus NYVAC strains] are the most promising vectors . They are ideal candidate vectors due to their large DNA-packing capacity and their thermal and genetic stability . The NYVAC vector has been shown to induce CD4 + T cell-dominant responses, and MVA induces", "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: The first human infections were identified through a surveillance system for pneumonia of unknown aetiology, and all of the earliest infections therefore had Modelling studies incorporating healthcare capacity and processes pneumonia. It is well established that some infections can be severe, particularly in older adults with underlying medical conditions , but based on the generally mild clinical presentation of 2019-nCoV cases detected outside China, it appears that there could be many more mild infections than severe infections. Determining the spectrum of clinical manifestations of 2019-nCoV infections is perhaps the most urgent research priority, because it determines the strength of public Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: In an analysis of the first 425 confirmed cases of infection, 73% of cases with illness onset between 12 and 22 January reported no exposure to either a wet market or another person with symptoms of a respiratory illness . The lack of reported exposure to another ill person could be attributed to lack of awareness or recall bias, but China's health minister publicly warned that pre-symptomatic transmission could be occurring . Determining the extent to which asymptomatic or pre-symptomatic transmission might be occurring is an urgent priority, because it has direct implications for public health and hospital infection control. Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "Passage: Currently, one urgent and critical challenge is to treat infected patients and save their lives. Several studies have roughly described the overall clinical features of 2019-nCoV patients . However, the more specific and classified clinical characteristics of the infected patients still require further investigation, particularly for those with severe symptoms, which is roughly estimated to be approximately 15-20 percent of totally confirmed cases based on the local data in our hospital. Clinically, for those severe patients, the main symptoms of 2019-nCoV pneumonia are fever, decreased white blood cell and lymphocyte count, increased C reaction protein and abnormally expressed cytokines . Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: more than 75,000 infections may have occurred in Wuhan as at 25 January 2020 , and increasing numbers of infections continue to be detected in other cities in mainland China and around the world. A number of important characteristics of 2019-nCoV infection have already been identified, but in order to calibrate public health responses we need improved information on transmission dynamics, severity of the disease, immunity, and the impact of control and mitigation measures that have been applied to date.", "Title: A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures\nPassage: Many computational thermodynamics-based methods find the structures with the minimum free energy from the set of all possible structures, when each structure feature is assigned a free energy value and the energy of a structure is calculated as the sum of the features' energies. There has been significant success in prediction of pseudoknot-free secondary structures . While many small RNA secondary structures are pseudoknot-free, many biologically important RNA molecules, both in the cell , and in viral RNA are found to be pseudoknotted. Title: A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures", "Passage: Many computational methods for predicting the secondary structure of an RNA molecule are based on models of the free energy of loops 48] . Table 1 summarizes the energy constants and functions used in our energy model for pseudoknotted structures. The values of these energy parameters are those of the DP09 parameter set of Andronescu et al. , used by the HotKnots V2.0 prediction software. Title: A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures\nPassage: more modest but still positive improvement in accuracy when further structural information is provided. Title: Predicting pseudoknotted structures across two RNA sequences", "Passage: When it comes to pseudoknots, many structures have been published based on a secondary structure predicted by free energy minimization. These predicted secondary structures are used as a working model and refined using experimental techniques such as chemical and enzymatic probing. However, the native structure remains unsolved unless tertiary structure determination methods such as X-ray crystallography are used. Testing structures that are based on computer predictions with no experimental support creates a bias in the benchmark and will be avoided in this evaluation.", "Title: Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro\nPassage: days . The PPRV genome of approximately 16 kilobases encodes six structural proteins, namely, the nucleocapsid , phospho , matrix , fusion , haemagglutinin and large proteins in the 3\u2032 to 5\u2032 direction ; two non-structural proteins are also encoded due to the RNA editing of the phosphoprotein gene. Four different lineages of PPRV have been defined worldwide based on the molecular epidemiology of the \"N\" and \"F\" gene sequences of the virus . PPRV is currently endemic in most of Africa, the Middle East, South Asia and China and causes significant economic losses . Title: Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization", "Passage: For the convenience of introducing mutations into the UFS region, the Asc I-SnaB I fragment from p4-Dualstop-SP-IRES-Rluc-Rep, which contained the SP6 promoter region and the DENV4 5 0 UTRcapsid ORF sequence, was engineered such that the sequence corresponding to the 70-107 nt region of the DENV4 genome was substituted by the following: 5 0 -CTCCTCACACATACGTAA TGGGGAGGAG-3 0 . This engineered fragment contained two inversely positioned BseR I sites and was cloned into pGEM-T easy to generate the cloning cassette vector, pBseRI-Dualstop-04. DNA oligos containing the desired mutations of the UFS were annealed and ligated with BseR I-digested pBseRI-Dualstop-04 to acquire Title: Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization", "Passage: The DENV2 and DENV3 5 0 end sequences were acquired by RT-PCR using the DENV2 strain NGC and the DENV3 strain 80-2 RNA as templates respectively, and cloned into pMD-19T-simple . The 5 0 end sequence of DENV1 strain WestPac was chemically synthesized and cloned into pUC57 by Thermo Fisher Scientific. The SP6 promoter sequence was placed upstream of the DENV1 5 0 end sequence. These constructs, together with the JEV infectious clone pAJE70 , which contains the 5 0 UTR-C-coding region of strain SA-14-14-2 , were utilized to amplify the DNA templates for in vitro transcription. The infectious clone Title: Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro", "Passage: extraction kit and purified according to the manufacturer's recommendations, and cDNA synthesis was performed using EasyScript First-Strand cDNA SuperMix according to the manufacturer's instructions. For PPRV-specific detection, a primer pair targeting the region corresponding to the P gene was used. Real-time RT-PCR was performed using TransStart Top Green qPCR SuperMix and an iQ5 iCycler detection system . The recombinant plasmid containing the PPRV P gene was used to construct a standard curve for calculating the viral copy number in different samples.", "Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus\nPassage: Preferred respiratory samples for infl uenza testing include nasopharyngeal or nasal swab, throat swab and nasal wash or aspirate, depending on which type of test is used. Samples should be collected within the fi rst 4 days of illness. Routine serological testing for infl uenza requires paired acute and convalescent sera, does not provide results to help with clinical decision-making. Serological testing results for human infl uenza on a single serum specimen is not interpretable and is not recommended. All respiratory specimens should be kept at 4\u00b0C for no longer than 72 hours before testing and ideally should be tested Title: Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?", "Passage: Samples were collected in viral-transport medium . A 200\u03bcl aliquot was stored at 4\u00b0C for no longer than 48 hours until analysis. The rest of the sample was stored at -80\u00b0C for further amplification and sequencing. RNA was extracted in a Nuclisens EasyMAG system by following the manufacturer's instructions. Pandemic influenza A pH1N1 was detected by real-time reverse transcriptase polymerase chain reaction by following the WHO/CDC protocol in a Stratagene MX3000 thermocycler . Those samples rendering indeterminate results were tested again with the RealTime ready Inf A/H1N1 Detection Set . Influenza B was detected by using the RealTime ready Influenza Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: In hospitalized patients receiving invasive mechanical ventilation in whom influenza is suspected, but not yet diagnosed, influenza testing should be performed on endotracheal aspirate specimens instead of those collected from the upper respiratory tract . Molecular testing, including RT-PCR for influenza viruses can also be performed on bronchoalveolar lavage fluid if collected for the testing of other pathogens. Blood, plasma, serum, cerebrospinal fluid, urine, and stool samples have very low diagnostic yield and are not recommended for influenza testing . Diagnostic test results on specimens collected from non-respiratory sites should not be used for clinical decision making even for patients Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: Novel H1N1 infl uenza virus detection can also be achieved by inoculating the clinical specimen on MDCK cells for virus isolation with subsequent characterization by hemagglutination inhibition and neuraminidase inhibition tests using monospecifi c antiserum. Although the cell culture method is sensitive, it requires viable virus, needs expertise and at least 6-8 days to grow the virus to a level where cells are examined for cytopathic effect . Virus isolation is not only labor-intensive it is timeconsuming also and requires a week for declaring a sample positive or negative hence not appropriate for an epidemic situation.", "Title: Delivery Systems for Intradermal Vaccination\nPassage: thereby enabling improved immunogenicity and simpler patient administration. Title: Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection", "Passage: Some lipid-based preparations have the advantage of being lyophilized, thus allowing to simplify the logistics usually necessary for cold chain. Indeed, some of these formulations can be stored at room temperature for several months and can be administered in such form via the nasal, oral, or sublingual routes. Dry powder nasal vaccines have already been tested , oral delivery of capsules is not a problem , and many allergy-related immunotherapy tablets have been considered for sublingual administration . Moreover, lipid-based preparations can be aerosolized, which might represent an alternative procedure to keeping stable vaccine preparations. Overall, great expectations are coming Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: Delivery of recombinant adenoviral vaccines to either the nasal or intestinal mucosa is an attractive vaccination strategy for many reasons. Vaccines administered in this manner will offer improved safety with respect to disease transmission and needle-stick injuries among health care workers, significant issues of concern in developing countries where the demand for many vaccines is high . Mucosal administration of vaccines reduces the pain associated with vaccination, eliminates the need for specialized training programs for large vaccination campaigns and makes selfadministration of the vaccine possible. This route of administration may also significantly reduce systemic toxicity associated with recombinant adenovirus despite Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: B10.BR mice were immunized with 1610 10 particles of recombinant virus per mouse either by intramuscular injection in the right hindlimb, or by oral gavage using oral feeding needles . For nasal immunization, mice were anesthetized with isoflurane. Once anesthesia was achieved, 1610 10 particles of virus slowly delivered as a bolus into the nostrils using a standard micropipette as previously described .", "Title: Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study\nPassage: the GMT gradually decreased from 12 to 60 months post-pandemic vaccination, although it persisted above the protective threshold . Title: Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study\nPassage: time point , which then decreased to HI titer <40 at 7 months . Title: Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study", "Passage: During the 2010/2011-2013/2014 seasons, HI antibodies were significantly boosted at 21 days after each IIV, and gradually waned over 3, 6, and 12 months post-vaccination, although they persisted above the HI titer of 40 in both the repeated and the occasional groups . Antibody responses and geometric mean ratios post-IIV during the 4 seasons were not significantly different between the repeated and occasional groups , although slightly higher HI titers were always observed in the occasional group. Furthermore, no significant differences were detected in HI The GMR is shown for each time point above the graph. The dotted line indicates Title: Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study", "Passage: During the 60-month follow-up of the single group with no susbsequent IIV, the GMT was boosted at 21 days after pandemic vaccination, waned throughout 3, 6, and 12 months, then increased significantly from 12 to 24 months , and gradually declined from 24 to 60 months . The increased GMT at 24 months without revaccination indicated that exposure or infection from circulating H1N1pdm09 viruses during the 2010/2011 season may have occurred.", "Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Recently, lactic acid bacteria presenting influenza virus antigens have been studied . For mucosal immunization, LAB is a more attractive delivery system than other live vaccine vectors, such as Shigella, Salmonella, and Listeria . It is considered safe and exhibits an adjuvant-like effect on mucosal and systemic immunity . Anchoring of the target protein to the cell surfaces of LAB is primarily intended to use in mucosal vaccines. The transmembrane protein pgsA is one of the poly-cglutamate synthetase complexes of Bacillus subtilis , which is a well-studied anchor protein is able to fuse the target protein to its C terminus Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Recently, lactic acid bacteria presenting influenza virus antigens have been studied . For mucosal immunization, LAB is a more attractive delivery system than other live vaccine vectors, such as Shigella, Salmonella, and Listeria . It is considered safe and exhibits an adjuvant-like effect on mucosal and systemic immunity . Anchoring of the target protein to the cell surfaces of LAB is primarily intended to use in mucosal vaccines. The transmembrane protein pgsA is one of the poly-cglutamate synthetase complexes of Bacillus subtilis , which is a well-studied anchor protein is able to fuse the target protein to its C terminus Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: LAB is an excellent candidate to be manipulated as a DNA vaccine carrier. LAB has been used in food fermentation for centuries and is a Generally Recognized as Safe organism . LAB is also resistant to acidic conditions in the gastrointestinal system and is able to deliver the vaccine to the intestinal area . Several LAB strains are famous as probiotic bacteria, such as Lactobacillus casei, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum and Lactobacillus reuteri. Probiotic bacteria reduce lactose intolerance symptoms, such as diarrhea and flatulence, which appear in lactose intolerant patients who consume milk. Probiotic bacteria also Title: Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection", "Passage: offers some advantages including those of being more convenient, lower cost, and less stress . In addition, lactic acid bacteria have been proposed as a live vehicle for the delivery of exogenous antigen proteins for mucosal immunization or for other therapeutic molecules. The biological functions of lactic acid bacteria are effectively combined with the immunogenicity of exogenous antigen genes . L. plantarum, a lactic acid bacteria, that can be used as a probiotic for animal gastrointestinal tracts, has many functions, such as maintenance of intestinal flora, enhancement of immunity, and promotion of nutrient absorption. L. plantarum can also act as", "Title: 1918 Influenza: the Mother of All Pandemics\nPassage: been sequenced so far. This is especially apparent when Title: Temporal Anomalies in Immunological Gene Expression in a Time Series of Wild Mice: Signature of an Epidemic?\nPassage: Against a background of apparent demographic increase during May-December 2008, significant decreases in trapping rate with respect the immediately preceding trapping occasions were only recorded immediately after the detection of extreme expression clusters . LMM analysis of trapping success data against time , allowing for positive autocorrelation between successive trapping sessions, suggested a highly significant increasing trend across May to December . A 2-level factor coding the two time intervals following the first detection of each extreme expression cluster and young-of-the-year cohorts in 2008 and also in a retrospective analysis of animals sampled at Cotgrave Forest by Jackson et al. Title: Suffering a Loss Is Good Fortune: Myth or Reality?", "Passage: than those of other groups , 20+-year alumni ), ps < 0.001. However, CLS scores recalled for the past did not differ significantly among the three groups. Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: nature of the two-way interaction . More specifically, the CLS was more positively related to SEI as people aged. However, this effect was not observed between CLS scores and SWB. This result indicated that age moderated the relationship between Chikui likelihood and SEI but not the relationship between Chikui likelihood and SWB.", "Title: Recent Advances in Droplet-based Microfluidic Technologies for Biochemistry and Molecular Biology\nPassage: Recently, biochemist and molecular biologist have particular interest in accomplishing the challenge of providing useful technologies which can be used in real life problems such as biomedical diagnosis and among other fields like drug screening and development. Probably one of the most used tools in these diagnostic field is PCR. DMF technologies update this procedure like we have already discussed in this paper. Digital PCR can provide a robustness and convenience which can mitigate the effects of PCR inhibitors in diluted samples, regardless of the form of template for forensic short tandem repeat typing at the single-cell/molecule level . Title: Advances in Directly Amplifying Nucleic Acids from Complex Samples", "Passage: seen in our time-course of blood testing, where isothermal techniques have surpassed PCR and RT-PCR in terms of the number of assays performed on whole blood samples. Title: Advances in Directly Amplifying Nucleic Acids from Complex Samples\nPassage: seen in our time-course of blood testing, where isothermal techniques have surpassed PCR and RT-PCR in terms of the number of assays performed on whole blood samples. Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase", "Passage: Epidemic of various infectious diseases seriously threaten global public health 14, 37 . Rapid diagnosis of involved pathogens plays a crucial role in the prevention and control of infectious diseases 3, 38 . Various new methods were developed for the detection and diagnostics of infectious diseases in the last two decades 39 . However, because of low sensitivity, low specificity, time-consuming and labor-consuming, and high costs, the practical application and commercial development of most methods are limited. To date, TaqMan probe-based qPCR is still the most robust method used in the detection and diagnostics of infectious diseases 14 .", "Title: Infections on the move: how transient phases of host movement influence disease spread\nPassage: balance the energetic costs of prolonged movement with immunosuppression , which clearly increases infection risk, and probably mortality, during host transience. Alternatively, adaptations that enhance immune function during periods of travel, particularly tolerance responses that aid host survival without resulting in parasite clearance , could facilitate infection spread. Such adaptations are evidenced by migratory birds that experience immune activation when preparing to migrate and by larger immune defence organs of migratory versus non-migratory bird species . Title: Infections on the move: how transient phases of host movement influence disease spread", "Passage: hosts, or as conditions during transience decrease exposure and/or cause deterioration of infections . Mechanisms that drive recovery include: movement through habitats unsuitable for infections, which may occur with protozoal infections during monarch butterfly migrations and with tick infections during ranging movements of livestock ; enhancement of immune function during periods of movement, which may occur in migratory red knots ; and dispersion of hosts that reduces contact, as evidenced by sea lice infections in migratory pink salmon . Mechanisms that increase the force of infection during transience include: movement through habitats with viable infective stages, which occurs with parasitic Title: Infections on the move: how transient phases of host movement influence disease spread", "Passage: This could also be done indirectly. For example, as immune function in ectothermic animals is strongly linked to body temperature, fitting migratory ectotherms such as amphibians and snakes with temperature sensors may provide insights into how host susceptibility varies during periods of movement. For larger-bodied mammals, GPS devices combined with accelerometers can identify critical periods of movement during which increased energy expenditure poses heightened infection risk . Title: Deconstructing host-pathogen interactions in Drosophila\nPassage: such seemingly disparate enzymatic activities, collaborate during infection ?", "Title: Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting\nPassage: Determining the transmission likelihood. We assume cases were classified correctly from case investigation as imported or locally-acquired based on recent travel history. Following this assumption, locally acquired cases could have both infected others and been infected themselves. However imported cases could only infect others, as we assume their infection was acquired outside of the country. There were no confirmed relapse cases in the dataset, and all cases were treated with primaquine and chloroquine after being detected. Treatment is initiated before cases are confirmed by microscopy . Active case detection is initiated locally following a confirmed case and in active foci Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: In our analysis of early cases, we observed transmission in two broad contexts: sporadic cases among travellers from China and cases who acquired infection due to subsequent local transmission in Europe . Our analysis shows that the time from symptom onset to hospitalisation/case isolation was about 3 days longer for locally acquired cases than for imported cases. People returning from affected areas are likely to have a low threshold to seek care and be tested when symptomatic, however delays in identifying the index cases of the two clusters in France and Germany meant that locally acquired cases took longer to Title: Description of two measles outbreaks in the Lazio Region, Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection", "Passage: In Italy, measles is a disease subject to mandatory notification, and according to the routine procedure, physicians must report suspected measles cases to their LHU within 48 hours of diagnosis. The local health authorities then report confirmed measles cases to the ASP monthly. At the beginning of the outbreaks this procedure was modified and physicians were asked to report suspected measles cases to both the local health authorities and ASP offices within 24 hours of diagnosis. Personnel of the LHUs performed epidemiological investigation of suspected cases including laboratory investigation and contact tracing. Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies", "Passage: The subject of whether a patient's interests would be best served by using a local immunoglobulin product, with antibodies to pathogens that are prevalent in the community, or have their home physician ship their usual product, for which the patient has a known tolerance is hotly debated. Patients with a history of intolerance to immunoglobulin products should not switch unless necessary. However, there are compelling reasons to consider a locally produced product when patients are in a foreign country for an extended period. It is known that antibodies to West Nile Virus have tracked with the distribution of the virus", "Title: On the possible role of robustness in the evolution of infectious diseases\nPassage: Bacterial resistance to antibiotics and other harmful substances \u0351e.g., heavy metals\u0352 often occurs through genes carried on plasmids: autonomously replicating DNA elements that are nearly ubiquitous in bacterial populations. Individual plasmids can sometimes include multiple genes conferring resistance to a variety of antibiotics. Also, plasmids can effectively spread within and among bacteria populations and species through conjugation \u0351cell-to-cell horizontal transfer\u0352. Together, these features create the capacity for rapid spread of multiple drug resistance in bacteria. Furthermore, plasmid-borne mechanisms \u0351e.g., postsegregational killing\u0352 often exist to ensure that vertical transfer \u0351plasmid inherit-ance\u0352 is reliably maintained across host-cell generations. For these reasons, plasmid Title: Molecular epidemiology and antimicrobial resistance features of Acinetobacter baumannii clinical isolates from Pakistan", "Passage: The macrolide resistance 2\u2032-phophotransferase msrmph operon was present in 15/25 isolates. The sulphonamide resistance genes sul2 and sul1 were detected in 14/25 and 11/25 isolates, respectively, with 3 isolates having both sul2 and sul1. The tetracycline resistance genes tet, tet, and tet were detected in 9/25, 2/25, and 1/25 isolates, respectively, with no cases of overlapping. Other resistance genes, such as floR, catA1, cmlA5, and catB8 , dfrA7 and dfrA1 , and arr-2 had low rates of occurrence ranging between 1/24 and 4/24 . Title: Molecular epidemiology and antimicrobial resistance features of Acinetobacter baumannii clinical isolates from Pakistan", "Passage: Class A extended-spectrum \u00df-lactamase genes were detected in 14/25 of the isolates, among which bla PER-1 , bla TEM-1D , bla GES-11 and bla PER-7 were carried by 5, 5, 3, and 1 isolate, respectively. There was no co-existence of more than one class A \u00df-lactamase gene per isolate. All the isolates carried aminoglycoside resistance genes. Each isolate carried between 2 to 7 aminoglycoside resistance genes. The occurrence rates ranged from 20/25 for aphA6a and strB, 16/25 for strA, 13/25 for aacC1, 8/25 for aphA1b, 7/25 for aadA1, 4/25 for aphA6b, aadB, and aacA4, and 1/25 for aacC2. The 16S Title: Changing Priorities in Vaccinology: Antibiotic Resistance Moving to the Top\nPassage: which bacteria proliferate and mutate, allowing the drug to select the resistant variants.", "Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology\nPassage: \u2022 We rephrased the definitions in a way that for serologic confirmation the necessity for two samples is clearly apparent at the beginning of the phrase. Title: Mapping the drivers of within-host pathogen evolution using massive data sets", "Passage: We have addressed these concerns by sub-sampling 10% and 1% of the reference data in Simulation Study 2 . In addition, the synthetic experiments using the Botswana data also examine the impact of changing the reference panel size and composition. We find that with 10k samples, in the Birth-Death model simulation, sensitivity is little affected . With 1k samples , sensitivity is further reduced . The LOO approach only adds value when the reference data set is of comparable size to the query set . However, in the extreme case of no reference data, the LOO approach performs well . Title: Near-Patient Sampling to Assist Infection Control\u2014A Case Report and Discussion", "Passage: The other related, practical issue is then to define what the clinically relevant threshold should be for the limit of detection of any molecular assay used to test such air samples. The following example illustrates some of these issues. Note that the figures discussed are for illustrative purposes only but the methods and equipment are based on some of the authors' current experiments. Title: Single\u2010cell transcriptomics reveals distinct inflammation\u2010induced microglia signatures\nPassage: 1.a. How was the sample size chosen to ensure adequate power to detect a pre--specified effect size? 1.b. For animal studies, include a statement about sample size estimate even if no statistical methods were used.", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: per million between 1981 and 1998, to 66 per million in 2005 . These trends have been reversed since the introduction of pneumococcal conjugate vaccination-13. Data from the United States suggest that empyema decreased by 50% in children younger than 5 years ; similarly, data from the United Kingdom and Scotland showed substantial reduction in pediatric empyema following pneumococcal conjugate vaccination-13 introduction . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Empyema is a rare complication of pneumonia. An increased incidence of empyema in children was noted in some high-income countries following pneumococcal conjugate vaccination-7 introduction, and this was attributed to pneumococcal serotypes not included in pneumococcal conjugate vaccination-7, especially 3 and 19A . In the United States, evidence from a national hospital database suggests that the incidence of empyema increased 1.9-fold between 1996 and 2008 . In Australia, the incidence rate ratio increased by 1.4 times when comparing the pre-pneumococcal conjugate vaccination-7 period to the post-pneumococcal conjugate vaccination-7 period . In Scotland, incidence of empyema in children rose from 6.5 Title: Ventilator associated pneumonia and infection control", "Passage: influenzae and S. aureus . In a recent meta-analysis that searched 33 randomized controlled trials published from 1984 to 1996, significant reductions in the incidence of respiratory tract infections and in total mortality were determined . Also in this meta-analysis and in the other recent prospective, randomized studies, it was mentioned that using only topical antibiotics reduced respiratory infections, but did not influence the survival . Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: the team can detect early the complications, solve them and create a safety atmosphere for the patient, the family and the staff in charge. In the 2nd group, our study revealed the following complications: complication of subcutaneous emphysema -6 cs , but pneumomediastinum -2 cs , lobar emphysema -1 cs , suppurations -2 cs , situations that were resolved. All children received a special critical care under the Protocol of pneumonia prophylaxis associated with artificial ventilation: gentle suctioning of secretions with closed suction systems after cuffinflation. Placing on 30\u00b0and oral hygiene for 2-3 times/day being mandatory for each one. Also,", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: The filamentous phage particle is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups . The regularity of the phage pVIII lattice and its diversity of chemically addressable groups make it an ideal scaffold for bioconjugation . The most commonly used approach is functionalization of amine groups with NHS esters , although this can result in unwanted acylation of pIII and any displayed biomolecules. Carboxyl Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: The filamentous phage particle is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups . The regularity of the phage pVIII lattice and its diversity of chemically addressable groups make it an ideal scaffold for bioconjugation . The most commonly used approach is functionalization of amine groups with NHS esters , although this can result in unwanted acylation of pIII and any displayed biomolecules. Carboxyl Title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy", "Passage: We identified filamentous EBOV particles 20 microns or longer, with a well ordered internal structure, and a helical nucleocapsid giving an internal ''herring-bone'' appearance using cryo-EM and cryo-ET . The nucleocapsid, as observed within intact viral particles, has a uniform helical structure and is enveloped by a membrane coated by an external layer of GP spikes. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes to a resolution of 14 \u00c5 as measured by the Fourier Shell Correlation 0.5 criterion. Virions are rarely straight. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: the phage filament Hess et al., 2012) , this pioneering FIGURE 3 | Chemically addressable groups of the filamentous bacteriophage major coat protein lattice. The filamentous phage virion is made up of \u223c2,500-4,000 overlapping copies of the 50-residue major coat protein, pVIII, arranged in a shingle-type lattice. Each monomer has an array of chemically addressable groups available for bioorthogonal conjugation, including two primary amine groups , three carboxyl groups and two hydroxyl groups . The 12 N-terminal residues generally exposed to the immune system for antibody binding are in bold underline. Figure adapted from structural data of Marvin, 1990 ,", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection Title: Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions,", "Passage: A novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 , was identified in December 2019 in the city of Wuhan, capital of Hubei Province, China, where cases were first confirmed . During December 2019\u2013February 2020, the number of confirmed cases increased drastically. Model estimates suggested that >75,000 persons were infected by January 25, 2020, and the epidemic had a doubling time of \u22486 days . By the end of January 2020, travel restrictions were implemented for Wuhan and neighboring cities. Nonetheless, the virus spread from Wuhan to other cities in China and outside the country. By February 4,", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection can exacerbate the disease. The review will serve to provide further understanding of viral induced exacerbation to identify potential pathways and pathogenesis mechanisms that may be targeted as supplementary care for management and prevention of exacerbation. Such an approach may be clinically significant due to the current scarcity of antiviral drugs for the management of viral-induced exacerbations. This will improve the quality of life of patients with chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases .", "Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection\nPassage: NS4B . It is thus conceivable that inhibitors targeting TMD of NS4B would perturb its function, leading to the suppression of viral RNA replication. In this study, the replacement of Q130 of NS4B with a basic amino acid conferred the resistance effect without suppressing JEV replication, suggesting that position 130 could tolerate a basic amino acid and that the basic amino acid might be involved in the interplay of NS4B with host proteins rather than viral proteins. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: NS4B . It is thus conceivable that inhibitors targeting TMD of NS4B would perturb its function, leading to the suppression of viral RNA replication. In this study, the replacement of Q130 of NS4B with a basic amino acid conferred the resistance effect without suppressing JEV replication, suggesting that position 130 could tolerate a basic amino acid and that the basic amino acid might be involved in the interplay of NS4B with host proteins rather than viral proteins. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: amino acid position 130 in transmembrane domain 3 of NS4B, i.e., position 2401 of the translated polyprotein in the JEV infectious cDNA clone . Sequence alignment of NS4B indicated that Q130 was conserved in all flaviviruses except YFV, which possessed a lysine at that position . The conserved Q130 of NS4B may account for the sensitivity of JEV, ZIKV, WNV, and DENV-2 to manidipine, as described above , while YFV showed resistance to the drug . Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection\nPassage: amino acid position 130 in transmembrane domain 3 of NS4B, i.e., position 2401 of the translated polyprotein in the JEV infectious cDNA clone . Sequence alignment of NS4B indicated that Q130 was conserved in all flaviviruses except YFV, which possessed a lysine at that position . The conserved Q130 of NS4B may account for the sensitivity of JEV, ZIKV, WNV, and DENV-2 to manidipine, as described above , while YFV showed resistance to the drug .", "Title: Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C\nPassage: However, the development of an effective HCV vaccine is hindered by several factors including the high genetic variability of the virus genome that gives rise to escape mutants which can evade both cellular and humoral host immune responses. Moreover, currently there are no suitable small animal models available that can mimic HCV infection of humans. Furthermore, humans and chimpanzees who have been previously treated and cured of hepatitis C could be re-infected after re-exposure to the virus . Conversely, there is some optimism that the development of a successful HCV vaccine might be possible because a proportion of infected individuals Title: Advanced Molecular Surveillance of Hepatitis C Virus", "Passage: The arrival of the second generation of direct-acting antivirals in 2011 resulted in improved SVR and a revolution in the field of anti-HCV therapy. Despite the development of drug resistance, the initial NS3-4A protease inhibitors telaprevir and boceprevir undoubtedly possessed advantages over dual IFN/RBV treatment . The success of both drugs was subsequently eclipsed by the licensing of simeprevir and sofosbuvir . The field of HCV therapy is rapidly evolving, and as a result, a large number of new antiviral drugs are currently being evaluated in advanced clinical trials . Title: Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C", "Passage: Health Organization estimates that as of 2015 only 20% of those infected with HCV were aware of their diagnosis and only 7.4% of those diagnosed with HCV were placed on treatment worldwide . Consequently, developing a safe, effective and inexpensive HCV vaccine is therefore necessary to control global infection and reduce the financial burden on healthcare systems. Title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection\nPassage: access in developing nations where the disease burden is high; therefore, there is still a need for the development of a prophylactic vaccine.", "Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections\nPassage: T-cell-secreted cytokines have also been implicated in the development of severe disease . Specifically, a theory known as original antigenic sin proposes that memory T-cell populations with low avidity for the infecting virus of a heterologous secondary infection cause a strong pro-inflammatory response, as would any memory T-cell population activated by a secondary infection. Yet, because of their low avidity, the ability of these T cells to lyse infected cells, and thereby to protect against viral infection, may be poor . In support of OAS, a study of dengue virus-specific T-cell responses in Thai children showed that the majority of Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: transgenic mice, heterologous secondary infections responses directed to serotype-specific epitopes were impaired, but responses to conserved epitopes were not, suggesting that heterologous secondary infections are associated with a limited T-cell response . Dung et al. further documented a temporal mismatch between CD8 \u00fe T-cell activation and vascular leakage, suggesting that T-cell-secreted cytokines do not contribute to the development of severe disease. Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: biologically in the context of a phenomenon known as antibody-dependent enhancement , which proposes that antibodies from a first infection cross-react with virus from a secondary infection, but lead to incomplete neutralization. The resulting partially neutralized immune complexes are thought to enhance viral entry into Fc-receptor bearing target cells, and, as a result of this increased viral infectivity, lead to higher viraemia . While an increased viral infectivity rate could reproduce shorter times to peak viraemia and higher levels of peak viraemia, this change could not reproduce a higher maximum viral clearance rate of at least 2.8 log 10 copies Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: disease. Of note, one of these models was statistically fit to individual-level patient data, with findings indicating that differences in viral dynamics between primary and secondary infections can be recovered by a higher viral infectivity rate during secondary infections. This result is consistent with evidence for the enhancement of viral infectivity as a result of increased levels of non-neutralizing antibodies during a secondary infection relative to a primary infection. The fourth model considers the dynamic interaction between free virus, uninfected cells, infected cells, B cells and antibodies . In this model, the effect of antibodies is either protective or enhancing,", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: The proposed method called FPASSA is a hybrid of FPA and SSA, in which the SSA is applied as a local search method for FPA. The proposed FPASSA starts by receiving the historical COVID-19 dataset. Then a set of solutions is generated where each of them represents the value for the parameters of the ANFIS model. Then the quality of each solution is calculated using the fitness value, and the solution that has the best fitness value is chosen to represent the best solution. Then the probability of each solution is computed. Then the current solution will be updated, either Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: In this section, the performance of the proposed FPASSA to predict the DS1 and DS2 is discussed. It can be concluded from Table 3 that the performance of FPASSA outperformed the compared methods in all measures, whereas the FPA is ranked second. The results of DS2 indicate that the FPASSA is ranked first in terms of RMSE, MAPE, R 2 , and the CPU time. Whereas, the PSO is ranked second, followed by the FPA, GA, then ABC. These results denote that the proposed method can optimize the parameters of the ANFIS model effectively and produce good results in terms Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: The rest of this study is organized as follows. The preliminaries of ANFIS, FPA, and SSA are described in Section 2. Section 3 presents the proposed FPASSA, and Section 4 presents the experimental setup and results. We conclude this study in Section 5. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: of the performance measures. Comparison results between the proposed FPASSA and other models to forecast COVID-19 are given in Table 4 . It can be concluded that the FPASSA outperforms other models. For example, by analyzing the results of RMSE, MAE, MAPE, RMSRE, and CPU time it can be observed that the FPASSA achieves the smallest value among the comparison algorithms, and this indicates the high quality of the FPASSA. Meanwhile, the FPA allocates the second rank, which provides better results than the rest of the methods.", "Title: Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever\nPassage: Lassa fever is an acute, viral hemorrhagic disease caused by Lassa fever virus , an enveloped RNA virus of the Arenaviridae. The disease was first recognized in the village of Lassa, Nigeria in 1969, which caused the death of two missionarynurses and the grave illness of a third . However, cases consistent with LF from the eastern part of Sierra Leone can be traced back to 1956 . Since the identification of LASV, humanto-human transmission has been documented in several nosocomial outbreaks and also for a review), leading to an initial perception that the virus was both highly contagious and Title: Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings", "Passage: Lassa fever virus causes acute viral haemorrhagic fever and is endemic to West Africa. Every year, approximately 100 000-300 000 people contract LASV, and 5000 people die from the infection. 1-3 The recent 2018 outbreak in Nigeria saw 423 confirmed cases with a case fatality rate of 25%, 4 5 and higher case fatality rates of up to 50%-70% have been reported. 6 7 Because of its potential for zoonotic and human transmission as well as difficulties in treatment and prevention, LASV is one of the high-priority pathogens identified on the WHO R&D Blueprint. 1 2 8 9 In June Title: Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings", "Passage: with LASV are asymptomatic or have mild symptoms of gradual fever, weakness and malaise, which often go unreported. 32 63 After a few days, roughly 20% of infections progress to headache, sore throat, cough, muscle/ joint pain, chest/abdominal pain, nausea, vomiting or diarrhoea. Indications of severe infection include facial swelling, fluid in the lung cavity, low blood pressure, petechiae and bruising, hepatitis and haemorrhaging of the conjunctival, gastrointestinal or mucosal tissue. Critically ill cases often present acute respiratory distress, shock, seizures, tremor, disorientation and coma. Death occurs within 14 days of onset for 15%-20% of severe cases. Young people and Title: Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever", "Passage: days for a 99:99% relative humidity. Also, Kern\u00e9is et al. identified that risk factors for positive seroconversion to LASV included either having received a medical injection, or having lived with someone displaying a haemorrhage, in the previous twelve months. No factors related to contact with rodents were identified. Similarly, McCormick et al. reported a lack of correlation between human LASV-specific IgG prevalence and either the level of domestic infestation by Mastomys, or the presence of LASV infection in Mastomys. These observations, taken together, suggest that a significant proportion of the burden of LF might be associated with human-to-human transmission.", "Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?\nPassage: Staphylococcus aureus colonizes persistently about 30% of the human population and typical niches include nares, axillae, and skin . They cause a variety of clinical manifestations ranging from mild skin infections to fatal necrotizing pneumonia. In the last decades, the pathogen became resistant to an increasing number of antibiotics and methicillin-resistant S. aureus is now a major cause of hospital acquired infections . Also the rise of community-acquired S. aureus strains is of special concern, because certain clones are associated with very severe infections . Recent prospective studies demonstrated an increase in proportion of communityacquired methicillin-sensitive S. aureus in severe Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: Staphylococcus aureus colonizes persistently about 30% of the human population and typical niches include nares, axillae, and skin . They cause a variety of clinical manifestations ranging from mild skin infections to fatal necrotizing pneumonia. In the last decades, the pathogen became resistant to an increasing number of antibiotics and methicillin-resistant S. aureus is now a major cause of hospital acquired infections . Also the rise of community-acquired S. aureus strains is of special concern, because certain clones are associated with very severe infections . Recent prospective studies demonstrated an increase in proportion of communityacquired methicillin-sensitive S. aureus in severe Title: A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus", "Passage: Staphylococcus aureus , one of the most common Gram-positive bacterium, causes a series of life-threatening diseases including sepsis, bacteremia and necrotizing pneumonia etc . In recent years, the treatment has become more and more difficult for infections caused by methicillin-resistant S. aureus , strains that are resistant to almost all the commonly used antibiotics . This fact urges pharmaceutical companies to develop new and effective prophylactic vaccines and immunotherapies in the battle against the bacterium. However, attempts at making S. aureus vaccines have so far been unsuccessful . This failure has been attributed partly to the feature of the bacterium, Title: Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus", "Passage: The most abundant source of heme iron in the mammalian host is hemoglobin, which mediates oxygen transport within circulating erythrocytes. The predominant adult hemoglobin consists of a tetramer containing two \u2423-globin and two \u2424-globin protein subunits, each of which binds a single heme molecule for the coordination of oxygen. The Gram-positive bacterium Staphylococcus aureus is well adapted to the human host and is a leading cause of skin and soft tissue infections, endocarditis, osteomyelitis, and bacteremia . To acquire iron during infection, S. aureus has evolved a high-affinity hemoglobin binding and heme extraction system, termed the iron regulated surface determinant", "Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus\nPassage: the nucleolar antigen B23, which is essential for their nucleolar localisation . Nevertheless, a recent study described that in contrast to Jurkat T-cells and other transformed cell lines where Tat is associated with the nucleus and nucleolus, in primary T-cells Tat primarily accumulates at the plasma membrane, while trafficking via the nucleus where it functions . While the regulation of their active nuclear import and/or export, as mediated by the karyopherin/importin family have been well described, the mechanisms distributing Tat and Rev between the cytoplasm, nucleoplasm and the nucleolus remains elusive . Importantly, two major studies by Machienzi et al. Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: Of importance, the nucleolus is also the target of viruses including HIV-1, hCMV, HSV and KSHV, as part of their replication strategy . Proteomics studies analysing the nucleoli of cells infected with Human respiratory syncytial virus , influenza A virus, avian coronavirus infectious bronchitis virus or adenovirus highlighted how viruses can distinctively disrupt the distribution of nucleolar proteins . Interestingly, both HIV-1 regulatory proteins Tat and Rev localise to the nucleoplasm and nucleolus. Both their sequences encompass a nucleolar localisation signal overlapping with their nuclear localisation signal , which governs their nucleolar localisation . Furthermore, Tat and Rev interact with Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: HIV-1 Tat is expressed early following HIV-1 genome integration and mediates the shift to the viral production phase, associated with robust proviral gene expression, viral proteins assembly and ultimately, virions budding and release. In this context and based on our results, we propose that Tat could participate in shaping the intracellular environment and metabolic profile of T cells to favor host biosynthetic activities supporting robust virions production. Indeed, we observed the distinct nucleolar enrichment of ribosomal proteins and enzymes associated with ribosomal biogenesis, which could be indicative of an increase in protein synthesis. With the notable exeption of RPL35A nucleolar Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: We observed the coordinated nucleolar enrichment of key components of the DNA replication, recombination and repair pathways by Tat. These include XRCC5 and XRCC6, HMGA1, APEX1, MCM2-7, SMC2, RFC1 and RFC2, while RFC4 was found to be significantly depleted. Interestingly, these cofactors have been associated with the efficiency of retroviral DNA integration into the host DNA or the integrity of integrated provirus . Whether the increased abundance of these factors within the nucleolus could be associated with their potential participation in the integration and maintenance of provirus gene integrity, remains to be determined.", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: The continued experience indicating the strong tissue tropism for endothelial cells, specifically, is among the several factors that make \u03b23 integrin an especially attractive candidate as an important in vivo receptor for hantaviruses. It is likely that hantaviruses arrive at their target tissues through uptake by regional lymph nodes, perhaps with or within an escorting lung histiocyte. The virus seeds local endothelium, where the first few infected cells give rise, ultimately, to a primary viremia, a process that appears to take a long time for hantavirus infections . By the time that secondary viremia emerges, the agents of the more Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: The main mechanism by which humans acquire hantavirus infection is by exposure to aerosols of contaminated rodent feces, urine, and saliva . This can occur when humans reside in areas in close proximity to those that rodents inhabit, live in areas infested with rodents, or when rodents invade human settings, which are more frequent in rural habitats. There is a long history of human co-existence with rodents, raising questions about the apparent recent increases in hantavirus-related illnesses, especially HCPS. Other than an apparent association with El Ni\u00f1o southern oscillation events in some regions , the recent increases in incidence of Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: Hantavirus is a virus transmitted mainly by rodent animals, mainly through urine, feces, and saliva and the aerosols produced by them, but rarely by the bites of infected animals . In recent years, the infection rate of hantavirus has increased in China and Europe . Hantavirus disease has turned out to be a newly identified but not a \"new\" disease in Germany . The clinical presentations may vary according to viral strains prevalence in different regions. In Asia, hantavirus infection by Hantan virus and Seoul virus targets mainly the human kidney and causes hemorrhagic fever with renal syndrome . In Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: environmental conditions seem to maintain the virus for longer periods outside its natural host allowing for indirect transmission . An alternative but uncommon route of virus transmission is by rodent bites . Field workers handling mammals are potentially at higher risk of exposure with hantavirus infections, although when quantified through serosurveys the absolute risk appears rather slight . A new study in Colorado suggests the possibility that a rodent bite may have been the proximate vehicle for outdoor transmission of SNV , which re-emphasizes the use of personal protective equipment during field work activities . As a particular case within", "Title: Health-seeking behavior and transmission dynamics in the control of influenza infection among different age groups\nPassage: A further limitation of our study is that we did not consider the influential factors on risk perception in an epidemic model. Hence, future research should explicitly consider a number of additional influential factors on risk perception within an epidemic modeling, including disease prevalence, network effects, and government and media health messages. Title: Essential epidemiological mechanisms underpinning the transmission dynamics of seasonal influenza", "Passage: Our assessment of goodness of fit is currently focused primarily on distribution of AARs and duration of epidemics, although we also take account of the sequence of strains and the age-distribution of cases . Future work will test our conclusions against a full description of the incidence data as well as against different choices of key features in the data, such as time of epidemic onset. Title: Introducing the Outbreak Threshold in Epidemiology\nPassage: to lie in the hundreds of thousands of susceptible individuals . Therefore, while only a small infected population is needed to trigger a full-scale epidemic, a much larger pool of individuals are required to maintain an epidemic, once it appears, and prevent it from fading out. This makes sense, since there tends to be more susceptible hosts early on in the outbreak than late on. Title: Viral factors in influenza pandemic risk assessment", "Passage: While the biological properties of a virus certainly play a large role in determining the pandemic risk posed by a strain, it is possible that even a virus perfectly adapted for human-tohuman transmission might fail to transmit extensively, due to ecological factors, chance, or both. Initiation of a pandemic requires not only a well-adapted virus but ecological opportunity to spill over into humans ), as well as a human population that is immunologically susceptible and sufficiently connected to establish ongoing transmission . Additional complexity arises from the fact that selection pressures for within-host proliferation and competition may diverge from those", "Title: Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics\nPassage: SILAC was achieved by growing 3T3-F442A preadipocytes in DMEM containing 5% dialyzed fetal bovine serum, 100 U/ml penicillin, 100 g/ml streptomycin, 0.25 g/ml amphotericin, and either Lys and Arg or Lys and Arg for at least seven cell doublings. For the cells grown in Lys and Arg, heavy isotope incorporation was evaluated by running a pilot digestion of the heavy isotope labeled cell extract followed by LC-MSMS analysis. The heavy isotope-labeled amino acids were incorporated into more than 99% of the cellular protein. Cells were washed and incubated in DMEM containing 1% BSA, 100 U/ml penicillin, 100 g/ml streptomycin, 0.25 Title: Kinetic Modelling of Infection Tracers [(18)F]FDG, [(68)Ga]Ga-Citrate, [(11)C]Methionine, and [(11)C]Donepezil in a Porcine Osteomyelitis Model", "Passage: Methionine is a naturally occurring essential amino acid. It can be labelled with the positron-emitter 11 C to obtain the chemically identical PET tracer methionine. Methionine is transported into cells via the Ltype amino acid transporter 1. It is crucial for the formation of proteins and is involved in the synthesis of phospholipids. The accumulation of methionine therefore reflects amino acid transport and protein synthesis. During cell replication, the demand for essential amino acids increases, as do protein and phospholipid synthesis. Although primarily used to detect malignant tumours , methionine is known from brain studies to accumulate in inflammatory tissue Title: Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins", "Passage: The structure of the C-terminal segment of the BLV LHR and the accumulated data suggest a key role for the conserved arginine in the mechanism of envelope-mediated membrane fusion. Moreover, our recent data indicate that the equivalent arginine residue, Arg422, of the HTLV-1 LHR-mimetic peptide is critical to inhibitory activity . Notably, for the HTLV-1 LHRbased inhibitor residues equivalent to Leu413, Arg416 and Leu419 are also of importance to the biological activity of the peptide . We therefore sought to establish whether or not the conserved arginine in the HTLV-1 LHR docks with the coiled coil in a similar manner Title: Cell-penetrating peptides as transporters for morpholino oligomers: effects of amino acid composition on intracellular delivery and cytotoxicity", "Passage: L-Arginine versus D-arginine. Arginine stereochemistry had little effect on the nuclear activity of the R 8 \u00c0 and 8 \u00c0PMO conjugates but affected the 8 \u00c0PMO . Replacement of the eight L-arginine residues in R 8 \u00c0 or 8 \u00c0PMO with D-arginine residues did not change the luciferase activity generated over the 1-5 mM . However, the replacement did cause a small but statistically significant decrease in the activity for 8 \u00c0PMO at 1 mM and 2 mM .", "Title: Monitoring Influenza Epidemics in China with Search Query from Baidu\nPassage: based on the composite search index for February and January, and the case count for January. We also examine the residuals to evaluate the adequacy of the model. Title: One Health in China\nPassage: as it resulted in reduced risks, financial savings, reduced time to detect disease outbreaks, as well as improved plant health services. Title: Early responses to H7N9 in southern Mainland China\nPassage: random dialling potentially limited response rate. Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: . Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.", "Title: Lessons learned from the 1918\u20131919 influenza pandemic\nPassage: The current international strain of novel H1N1 virus discovered in Mexico is derived from two unrelated swine viruses, one associated with a fourth generation of the 1918 human infl uenza virus with which acts to recombine the viruses and its progeny . Essentially the virus continues by shuffl ing its eight genes in the avian reservoir to eventually be passed to swine and other mammals before the encounter with humans. Seldom are there transfer of infl uenza between humans and avian. Pigs act as the \"transformers or converters\" for the various infl uenza viruses and let loose the world new Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: The current outbreak of swine infl uenza that originated in Mexico in March 2009 has spread to more than 80 countries causing more than 3,99,232 laboratory confi rmed cases of pandemic infl uenza H1N1 globally and over 4735 deaths reported to World Health Organization as of 11 October 2009 . The WHO declared pandemic alert stage 6 on 11 June 2009, indicating an ongoing infl uenza pandemic . The 2009 swine fl u virus designated H1N1 A/swine/California/04/2009 is not zoonotic swine fl u and is not transmitted from pigs to humans, but rather from person to person and has higher Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: 1918 swine H1N1 influenza which led to the 1918-1920 influenza pandemic. Its descendants include an H2N2 pandemic strain in 1957, which circulated until 1968 when it was replaced by H3N2 pandemic viruses. Among many subtypes of influenza A viruses , influenza A and A subtypes are currently circulating yearly among humans. Type C influenza cases occur much less frequently than that of A and B. Therefore, only influenza A and B viruses are included in seasonal influenza vaccines recommended every year by the WHO. Title: Influenza A H1N1 2009 (Swine Flu) and Pregnancy", "Passage: Although we are now in the post pandemic phase, the A H1N1 virus has now emerged as the predominant strain of virus in the seasonal influenza season that is currently affecting the northern hemisphere. Current experience in the United Kingdom shows that the population below the age of 65 years are worst affected by the complications of the flu and that the deaths associated with the flu are predominantly associated with the H1N1 virus. From October 2010 to early January 2011, 50 deaths were reported by the Health Protection Agency. Forty-five of these people died with the H1N1 strain and", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: DNA Vaccines\u2014How Far From Clinical Use?", "Passage: The delivery vector has to offer a sufficient capacity to efficiently package DNA/RNA per se, which is an obstacle especially for longer plasmid DNA , in order to enable delivery of a sufficient amount of molecules per target cell . The delivery system has to show stability against serum proteins that may form a protein corona around the NC and thereby affect its targeting and uptake efficiency . After uptake by the cell, the NC cargo has to evade endo/lysosomal degradation and to enter the cytoplasm by endosomal escape . While released mRNA is translated directly in the cytoplasm, Title: Recombinant vector vaccine evolution", "Passage: Evolution is not the only consideration in designing a recombinant vector vaccine, and the model helps us identify vaccine properties that promote efficacy. First the vaccine should elicit an immune response that rapidly clears the pathogen . Second, the vaccine should elicit a large response to this antigen. This requires that the antigen rapidly elicits immunity , and also requires a high vaccine viral load to generate a large response. Engineering this requires tackling a trade-off between avoiding vaccine clearance but allowing for rapid clearance of the pathogen . Vaccines designed to express the antigen in a form that is Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: comparison of the properties of several strains that are commonly used as DNA vaccine carriers is presented in Table 1 . , and inside the DCs, the antigen gene is expressed as protein, which will later be presented by class I or II MHC and delivered to CD4+ or CD8+ T cells.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: alter the local environment and contribute to current and future exacerbations. Future studies should be performed using metagenomics in addition to PCR analysis to determine the contribution of the microbiome and mycobiome to viral infections. In this review, we highlight recent data regarding viral interactions with the airway epithelium that could also contribute to, or further aggravate, acute exacerbations of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: As integration of the virology, microbiology and immunology of viral infection becomes more interlinked, additional factors and FIGURE 1 | Current understanding of viral induced exacerbation of chronic airway inflammatory diseases. Upon virus infection in the airway, antiviral state will be activated to clear the invading pathogen from the airway. Immune response and injury factors released from the infected epithelium normally would induce a rapid type 1 immunity that facilitates viral clearance. However, in the inflamed airway, the cytokines and chemokines released instead augmented the inflammation present in the chronically inflamed airway, strengthening the neutrophilic infiltration in COPD airway, and", "Title: Insights into the Evolution and Emergence of a Novel Infectious Disease\nPassage: Zoonotic emergence of novel human infections poses a significant risk to global public health. For example, the 'Spanish flu' pandemic of 1918 probably originated in birds and caused millions of deaths worldwide . While much less virulent, the subsequent influenza pandemics of 1957, 1968 and 2009 are potent reminders of the capacity of the influenza virus to cross the species barrier into humans. Many other pathogens share this capacity: the SARS outbreak of 2003 has been linked to bats and palm civets . In 2008, a novel arenavirus which killed four out of five patients in South Africa was linked Title: The origins of the great pandemic", "Passage: to reveal the answer, indirect methods including phylogenetics provide important clues, and we consider whether intense influenza activity as far back as 1915 in the USA may have been caused by viral strains closely related to the 1918 one. The influenza pandemic of 1918 was arguably the most intense outbreak of infectious disease in human history. It killed an estimated 50 million people worldwide, most of them within a period of just a few months during the autumn of that year . In the intervening century, a great deal has been learned about the nature of this pandemic, not least Title: The 1918 Influenza Pandemic: Looking Back, Looking Forward", "Passage: The influenza virus is remarkable for its ability to infect a variety of animal species, from bats to birds to mammals. Although successful cross-species transmission events may be rare, they play a key role in the genesis of new pandemic strains. Nelson and Worobey discussed different lines of evidence informing the origins of the 1918 virus, including the genetic make-up of the 1918 virus and other pandemic strains, the characteristics of influenza receptors across different influenza hosts, and the frequency of cross-species transmission events. They concluded that the pandemic virus must have emerged in mammals just before 1918, most likely Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Text: Emerging pathogens cause new or previously unrecognized diseases, and among them, emerging zoonotic diseases are a major concern among scientists studying infectious diseases at different spatial and temporal scales . Changes in biotic and abiotic conditions may alter population disease dynamics and lead to the emergence of zoonotic infections . During the last decades, several outbreaks of emerging and re-emerging viral pathogens have occurred, affecting both purely-local and worldwide/pandemic involvement of human populations. Among the conspicuous examples are influenza A, Ebola virus, hepatitis C virus, severe adult respiratory distress , coronavirus, and human immunodeficiency virus, which challenge prevention and", "Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: The most common viruses detected were RSV and rhinovirus accounting for almost 60% of all cases. Both viruses were reported previously by others as the major aetiology for respiratory viral infections in young children with rhinoviruses being recognized increasingly for their role in lower respiratory tract infections . Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Viral heterogeneity associated with ARIs is well established . In the past, human rhinovirus has been identified as the virus most frequently associated with respiratory illness with 30-50% of infections annually on average, and up to 80% of upper respiratory infections during the autumn outbreaks . After HRVs, coronaviruses , influenza, respiratory syncytial virus and parainfluenza viruses are the next most frequent. Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: In our study, leukocyte count was used as an indicator of inclusion criteria and it probably affected the positive rate. Viruses not considered in the study, for example coronaviruses, would underestimate the positive rate. Most studies showed that RSV or HRV was the most prevalent viruses in children with viral respiratory tract infection. 1 In this study, IAV was the most frequently detected respiratory virus, followed by RSV and HRV. IAV outbreak in 2009 could explain this shift. Data showed that about 60% of IAV infections were detected during the outbreak period. Studies showed that the H1N1 outbreak could change Title: Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection", "Passage: Acute respiratory viral infections are among the most common reasons for patient visits in primary and acute care settings . Many viruses cause such acute respiratory illness including human rhinovirus , respiratory syncytial virus and influenza. These viruses can be associated with a range of clinical severity from asymptomatic to mild, self-limited illness to respiratory failure and death. Influenza alone causes 25 to 50 million infections annually in the USA, resulting in several hundred thousand hospitalizations and 20-40,000 deaths .", "Title: TcdC Does Not Significantly Repress Toxin Expression in Clostridium difficile 630\u0394Erm\nPassage: The main virulence factors of the enteropathogenic C. difficile are the two large clostridial toxins, toxin A and toxin B . These toxins are glycosyltransferases that inactivate Rho, Rac and Cdc42, thereby disrupting the cytoskeleton and tight junctions of the cells, resulting in apoptosis . This induces an inflammatory response and degradation of the intestinal epithelial cell layer. Besides the genes encoding these toxins , the pathogenicity locus also contains genes encoding a sigma factor and a putative anti-sigma factor . In between the toxin genes the tcdE gene is situated, which encodes a putative holin protein . Interestingly, both Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA", "Passage: factors are the major clostridial toxins A and B . In addition, certain strains of C. difficile, including ribotypes 027 and 078, additionally encode a binary toxin . C. difficile is transmitted via the fecal-oral route. It is believed that spores are crucial to successfully infect new hosts, as they are able to withstand the harsh environment of the stomach, and survive antibiotic treatments that alter the endogenous flora, after which C. difficile can overgrow . Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA", "Passage: factors are the major clostridial toxins A and B . In addition, certain strains of C. difficile, including ribotypes 027 and 078, additionally encode a binary toxin . C. difficile is transmitted via the fecal-oral route. It is believed that spores are crucial to successfully infect new hosts, as they are able to withstand the harsh environment of the stomach, and survive antibiotic treatments that alter the endogenous flora, after which C. difficile can overgrow . Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA", "Passage: C. difficile is a Gram positive, anaerobic bacterium that is the causative agent of C. difficile infection ). Though many people are asymptomatically colonized by C. difficile, the bacterium can cause serious health problems, such as pseudomembranous colitis and toxic megacolon, under the influence of risk factors such as age and antibiotic use. As a result, CDI was long regarded a nosocomial infection. Recently, however, an increase in the cases of community acquired CDI can be observed . Outbreaks of CDI have been linked to so called hypervirulent strains, such as PCR ribotypes 027 and 078 . Its main virulence", "Title: Estimating the number of infections and the impact of non-\nPassage: Switzerland 3.2% Title: Estimating the number of infections and the impact of non-\nPassage: Switzerland measures fever symptoms.55 2/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: und verscharft die Massnahmen. Schweizerische Eidgenossenschaft Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain", "Title: Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak\nPassage: Third, the decline in reproduction number could be because many infections were asymptomatic and many symptomatic cases were not reported. The request to report any symptoms might not have reached all participants because of the event's large size and because participants came from many different countries. During norovirus outbreaks, asymptomatic cases occur; in almost half of the outbreaks in the Netherlands during 2002, stool samples from >1 healthy persons tested positive for norovirus . Volunteer and outbreak studies demonstrate that 30% of collected stool specimens of exposed, asymptomatic persons were positive for norovirus . However, both the proportion of asymptomatic Title: Pandemic (H1N1) 2009 among Quarantined Close Contacts, Beijing, People\u2019s Republic of China", "Passage: Among close contacts with pandemic 2009, \u224814.4% were asymptomatic. It is noteworthy that specimens from some close contacts tested negative for pandemic 2009 virus before quarantine, but those persons could shed the virus during quarantine without symptoms. Such infection could not be detected, and the proportion of subclinical infection was underestimated. Therefore, we calculated the proportion of subclinical infection by cross-sectional analysis of the subclinical infection of close contacts before quarantine, and we found that \u224817% of case-patients with pandemic 2009 were asymptomatic. Title: We should not be complacent about our population-based public health response to the first influenza pandemic of the 21(st )century", "Passage: This should not be surprising, as the finding that a high proportion of influenza infections are asymptomatic or afebrile was not new. Published experimental data from volunteer studies had previously shown that 33% of proven seasonal influenza infections were asymptomatic, but this varied by influenza type and subtype . In particular, as few as 37% of experimental infections with influenza A were associated with fever recorded as >37.8\u00b0C, while 30% were completely asymptomatic . Moreover, viral shedding in the presymptomatic phase of influenza infection has recently been confirmed to occur in approximately 1-8% of naturally acquired infections, in a study Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: Following previous works, presumably 33 per cent of the infected people are asymptomatic while the remaining 67 per cent show symptoms of infection . Of those who are symptomatic, 6 per cent are assumed critical and require hospitalization . The other 94 per cent will show only mild symptoms. For the critically ill, they are 50 per cent more infectious as compared with those showing mild symptoms, while the asymptomatic cases are 50 per cent less infectious. In the current model, we ignored the occurrence of deaths. However, it can be assumed that the death rate is directly proportional to", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: Respiratory viruses primarily infect and replicate within airway epithelial cells . During the replication process, the cells release antiviral factors and cytokines that alter local airway inflammation and airway niche . In a healthy airway, the inflammation normally leads to type 1 inflammatory responses consisting of activation of an antiviral state and infiltration of antiviral effector cells. This eventually results in the resolution of the inflammatory response and clearance of the viral infection . However, in a chronically inflamed airway, the responses against the virus may be impaired or aberrant, causing sustained inflammation and erroneous infiltration, resulting in the exacerbation Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: an immune response leading to infiltration of activated immune cells that further release inflammatory mediators that cause acute symptoms such as increased mucus production, cough, wheeze and shortness of breath. Among these agents, viral infection is one of the major drivers of asthma exacerbations accounting for up to 80-90% and 45-80% of exacerbations in children and adults respectively . Viral involvement in COPD exacerbation is also equally high, having been detected in 30-80% of acute COPD exacerbations . Whilst the prevalence of viral exacerbations in CRS is still unclear, its prevalence is likely to be high due to the similar Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Once the link between viral infection and acute exacerbations of chronic airway inflammatory disease was established, there have been many reports on the mechanisms underlying the exacerbation induced by respiratory viral infection. Upon infecting the host, viruses evoke an inflammatory response as a means of counteracting the infection. Generally, infected airway epithelial cells release type I and type III interferons, cytokines and chemokines such as IL-6, IL-8, IL-12, RANTES, macrophage inflammatory protein 1\u03b1 and monocyte chemotactic protein 1 . These, in turn, enable infiltration of innate immune cells and of professional antigen presenting cells that will then in turn release", "Title: A Vesicular Stomatitis Virus Replicon-Based Bioassay for the Rapid and Sensitive Determination of Multi-Species Type I Interferon\nPassage: was determined with a microplate reader. The IFN titer was calculated as the reciprocal of the last IFN dilution causing 50% inhibition of virus-induced CPE and was expressed as IFN units per volume. Alternatively, antiviral activity was calculated according to the following formula: Antiviral activity = 6100/. OD595 +IFN and OD595 2IFN represent the absorbance of IFN-treated and non-treated cells following infection with VSV and staining with crystal violet, respectively. OD595 Mock denotes the absorbance of non-infected cells. Title: Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity", "Passage: determined by p24 level and TCID50; briefly, 10-fold serial dilutions of concentrated viral supernatants were used to infect PBMCs from two donors preactivated for 3 days with 10 mg/ml of PHA. Half of the media was replaced on day 4, and 7 days after infection, supernatants were harvested and processed for p24 by ELISA. The Reed-Muench method was used to calculate the TCID50. For HIV infection, CD14+ monocytes were negatively selected using the EasySep Human Monocytes Enrichment Kit as per manufacturer's instructions. Isolated cells were transfected with 59pppRNA using Lyovec according to the manufacturer's protocol. Supernatants were harvested 24 h Title: A cell-based high-throughput approach to identify inhibitors of influenza A virus", "Passage: For evaluation assay of antivirals and high-throughput screening, 1 \u03bcL of each tested compound was added to cells and incubated for 2 h prior to infection, after which cells were infected with influenza A/WSN/33 virus at an MOI of 0.05. After a further incubation for 24 h at 37 1C, the cell supernatant was collected and measured for Gluc activity. In each 96-well plate ribavirin and DMSO were used as positive and negative controls, respectively. Title: Identification of Three Antiviral Inhibitors against Japanese Encephalitis Virus from Library of Pharmacologically Active Compounds 1280", "Passage: containing 1% DMSO were set on each plate as controls. After 120 h incubation, the percentage of CPE inhibition was calculated as previously described : Percentage of inhibition = / 6100. Each concentration was assayed in triplicate. Forty-eight hours post-infection, the viruses in each group were harvested by freezing/thawing three times and mixed in a tube. Then, 50 mL virus suspension was inoculated into BHK-21 cells in 12-well plates for the plaque assay, as previously described .", "Title: Host resilience to emerging coronaviruses\nPassage: Corticosteroids are broadly immunosuppressive and have many physiological effects . Several recent studies have suggested that other compounds could be useful in increasing host resilience to viral lung infections. A recent paper demonstrates that topoisomerase I can protect against inflammation-induced death from a variety of viral infections including IAV . Blockade of C5a complement signaling has also been suggested as a possible option in decreasing inflammation during IAV infection . Other immunomodulators include celecoxib, mesalazine and eritoran . Another class of drugs that have been suggested are statins. They act to stabilize the activation of aspects of the innate immune Title: Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia\u2014a new therapeutic strategy?", "Passage: IVs are enveloped single-stranded negative-sensed RNA viruses, divided into three genera A, B, and C . They cause respiratory infections in humans and not only occur seasonally but also occur in recurrent pandemics . IV A is further divided into subtypes that differ in the surface glycoproteins hemagglutinin and neuraminidase . The viral HA serves to attach to host cells; the NA protein cares for viral release after replication . Due to the segmented nature of its genome and a high rate of mutations during replication, seasonal IVs show an annual change of antigenic qualities in the HA and NA Title: Host resilience to emerging coronaviruses", "Passage: pathogen itself. Given the damage that pathogens can cause this focus on rapid pathogen clearance is understandable. However, an equally important medical intervention is to increase the ability of the host to tolerate the direct and indirect effects of the pathogen, and this is an area that is just beginning to be explored . Damage to the lung epithelium by respiratory pathogens is a common cause of decreased resilience . This review explores some of the probable host resilience pathways to viral infections, with a particular focus on the emerging coronaviruses. We will also examine factors that make some patients Title: Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia\u2014a new therapeutic strategy?\nPassage: PU.1, transcription factor PU.1; ROS, reactive oxygen species; RSV, respiratory syncytial virus; TGF \u03b1, transcriptional growth factor \u03b1", "Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region\nPassage: Two hundred forty-eight of 11,399 patients tested positive for HBoV1 infection. Of the HBoV1-positive patients, 112 were co-infected with other pathogens, most frequently with RSV . The median age was 1 year . The male-to-female ratio was 2.54:1 in HBoV1-positive patients and 1.81:1 in HBoV1-negative patients . Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: In the current study, 86.5% of patients were under the age of 5 years, with a median age of 1.75 years, indicating that infants and young children were most at risk of ARI, consistent with previous reports . Overall, 49.2% of patients tested positive for one or more respiratory pathogens, 2.2% of patients were tested with HBoV1 infection . A higher prevalence of HBoV1 was detected in male patients compared with female patients , consistent with previous reports . Title: Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK", "Passage: A total of 7.4% of the samples tested were positive for HBoV. No statistically significant differences were seen in the prevalence of HBoV between cases and asymptomatic controls, POR = 0.79 . Peak HBoV infection was observed in children under the age of 5, both in cases and controls, with significantly higher HBoV incidence in children between 1 and 4 in asymptomatic controls than in the cases of gastroenteritis . The number of HBoV positives in older age groups was too small for meaningful statistical analysis. Title: Human Bocavirus in Patients with Respiratory Tract Infection\nPassage: Ninety-three of the 1,926 nasopharyngeal aspirates obtained from patients of all age-groups were positive for HBoV. Our detection rate is similar to that stated in other reports . Generally, HBoV is detected in fewer than 8% of respiratory specimens ; however, higher detection rates ranging from 10.3% to 19% have been reported .", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Researchers have estimated that almost 75% of zoonotic diseases are associated with landcover and land-use changes . LCLUC such as peri-urbanization and agricultural diversification frequently result in more diverse and fragmented landscapes . The importance of landscape pattern, including diversity and associated processes, which equate to host species' habitat size and distribution, and thus pathogen transmission dynamics is axiomatic though the specific mechanisms depend on the disease . Landscape fragmentation produces ecotones, defined as abrupt edges or transitions zones between different ecological systems, thought to facilitate disease emergence by increasing the intensity and frequency of contact between host species Furthermore, Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: Researchers have estimated that almost 75% of zoonotic diseases are associated with landcover and land-use changes . LCLUC such as peri-urbanization and agricultural diversification frequently result in more diverse and fragmented landscapes . The importance of landscape pattern, including diversity and associated processes, which equate to host species' habitat size and distribution, and thus pathogen transmission dynamics is axiomatic though the specific mechanisms depend on the disease . Landscape fragmentation produces ecotones, defined as abrupt edges or transitions zones between different ecological systems, thought to facilitate disease emergence by increasing the intensity and frequency of contact between host species Furthermore, Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: fragmentation of natural habitat tends to interrupt and degrade natural processes, including interspecies interactions that regulate densities of otherwise opportunistic species that may serve as competent hosts , although it is not clear if reduced species diversity necessarily increases pathogen transmission . Rarely has research connected land-use diversification to final health endpoints in humans or livestock; this study attempts to link land-use diversity with HPAI H5N1 outbreaks. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: fragmentation of natural habitat tends to interrupt and degrade natural processes, including interspecies interactions that regulate densities of otherwise opportunistic species that may serve as competent hosts , although it is not clear if reduced species diversity necessarily increases pathogen transmission . Rarely has research connected land-use diversification to final health endpoints in humans or livestock; this study attempts to link land-use diversity with HPAI H5N1 outbreaks.", "Title: Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation\nPassage: Given the indolent nature of CLL and other low grade lymphomas, the spectrum of available treatments today and the associated prolonged survival of affected patients, it is likely that radiologists will encounter more imaging studies of patients treated with these novel drugs. It is necessary to be familiar with the expected response patterns and common toxicities associated with targeted agents to optimize care of this growing population. Ethics approval and consent to participate Not applicable. Title: Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation", "Passage: reveals significant decrease in the lymphadenopathy with the axillary node now measuring less than a centimeter in short axis . c Axial CT of the chest obtained in arterial phase as a part of restaging examination in the same patient reveals focal ground glass opacity in the right upper lobe raising concern for Ibrutinib pneumonitis hepatotoxicity and pneumonitis . Idelalisib is also associated with increased risk of opportunistic infections such as pneumocystis jirovecii . Title: A Computer-Aided Detection System for Digital Chest Radiographs", "Passage: Each biomedical image technique is appropriate for certain diagnostics. For example, MRI enables the spatial localisation required for cross-sectional imaging whereas ultrasound images allow physicians the visualisation of soft tissues and have revolutionised obstetric care . However, digital radiology is still the backbone of diagnostic bioimaging, mainly due to three reasons: its capability to detect unsuspected pathologies; being not invasive; and having a low radiation dose and low cost . Title: Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation", "Passage: Contrast-enhanced CT is the imaging modality of choice in CLL/SLL. Most commonly, CLL/SLL patients demonstrate multi-station mildly to moderately enlarged lymph nodes, with or without splenomegaly or hepatomegaly. Bulky nodes and confluent adenopathy is commonly seen during relapses or, as noted above, in patients at presentation with 17p or 11q deletion . Rare sites of CLL involvement have been reported, including the central nervous system . PET-CT is not commonly performed in CLL as it is not a b c Fig. 1 69-year-old woman at the time of diagnosis with CLL. a Axial CT image of the neck obtained during", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: inflammatory nature of these diseases . One of the reasons for the involvement of respiratory viruses' in exacerbations is their ease of transmission and infection . In addition, the high diversity of the respiratory viruses may also contribute to exacerbations of different nature and severity . Hence, it is important to identify the exact mechanisms underpinning viral exacerbations in susceptible subjects in order to properly manage exacerbations via supplementary treatments that may alleviate the exacerbation symptoms or prevent severe exacerbations. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: . Furthermore, the humanized mouse model that possess human immune cells may also serves to unravel the immune profile of a viral infection in healthy and diseased condition . For milder viruses, controlled in vivo human infections can be performed for the best mode of verification of the associations of the virus with the proposed mechanism of viral induced acute exacerbations . With the advent of suitable diseased models, the verification of the mechanisms will then provide the necessary continuation of improving the management of viral induced acute exacerbations. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children", "Passage: xacerbations are the primary cause of morbidity and mortality in children with asthma and occur despite current treatments. It has been established that the majority of exacerbations are provoked by viral respiratory infections, most notably rhinoviruses ; however, exacerbations also occur in the absence of infections 1,2 . Furthermore, even in children with severe asthma, the majority of respiratory infections do not progress to exacerbation 3 . The fundamental question of why some but not all colds lead to exacerbations has not been fully answered, and the similarities and differences between the mechanism of virus-associated and nonviral exacerbations are unknown.", "Title: A Rationally Designed TNF-\u03b1 Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice\nPassage: TNF-\u03b1 is a pleiotropic pro-inflammatory cytokine playing pivotal roles in both physiological and pathological processes . The primary function of TNF-\u03b1 is to regulate immune cells in inflammation as well as in protective immune responses against a variety of infectious pathogens. As a master regulator of pro-inflammatory cytokines such as IL-1\u03b2, IL-6 and GM-CSF , over expression of TNF-\u03b1 causes a variety of chronic inflammatory diseases including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis and psoriasis, and so on . Title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus", "Passage: Tumor necrosis factor alpha is a key cytokine for controlling severe IAV infections. It regulates two main antiviral functions: the induction of the NFkB pathway, which ultimately controls expression of several inflammatory cytokines and apoptosis through multiple signaling cascades . TNF upregulation during IAV infections correlates with infection severity, especially following highly pathogenic IAV-infections . Mice treated with anti-TNF Abs showed reduced disease burden; however, the authors of that study reported no effect on viral replication . Title: A Rationally Designed TNF-\u03b1 Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice", "Passage: Almost all known cytokines are present in the RA synovial fluid, among which TNF-\u03b1 is the first cytokine proved to be effective therapeutic target . In recent years, the immune-regulatory function of GM-CSF has been shown to play crucial roles in driving the development of many autoimmune diseases . GM-CSF or its receptor-targeted therapies have been shown highly effective and remarkably safe in treatments of many autoimmune diseases, in particular, RA . Of note, antigen-specific regulatory T cells activated by therapeutics antagonizing TNF-\u03b1 or GM-CSF have been shown play major immune suppressive roles in RA and other autoimmune diseases . Title: Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker", "Passage: Tumor necrosis factor alpha-induced protein 6 is a secreted glycoprotein expressed by epithelial cells and leukocytes under normal and inflammatory conditions. Its anti-inflammatory function is well established in different inflammatory conditions such as osteoarthritis, and it is detectable in serum samples from patients with autoimmune disorders . Recently, transcriptional profiling of blood from colorectal patients and normal controls by qRT-PCR identified TNFAIP6 as a biomarker for colorectal cancer . This study shows that TNFAIP6 mRNA is elevated in peripheral blood cells of colorectal cancer patients. Here, we investigated the protein levels of TNFAIP6 in colon cancer cells and adjacent normal", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: mortality. It remains unclear if this group are uniquely affected by MERS-CoV or if other respiratory virus infections, including those from HCoVs, produce a similarly serious impact. In South Korea, a single imported case created an outbreak of 185 cases and 36 deaths that had a disproportionate impact on economic performance, community behaviour and trust in government and the health care system. Household human-to human transmission occurs but is also limited. Educational programs will be essential tools for combatting the spread of MERS-CoV both within urban and regional communities and for the health care setting. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: or worse, and secondary bacterial infections have been reported . Disease can progress to acute respiratory distress syndrome and multiorgan system failure . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported . General supportive care is key to managing severe cases . Children under Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a sputum sample was taken and tested positive for MERS-CoV on the 20 th , triggering transfer to the designated isolation treatment facility. Over a period of 10 days, the index case was seen at three different hospitals, demonstrating a key feature of \"hospital shopping\" that shaped the South Korean outbreak. Approximately 34 people were infected during this time . In total 186 cases were generated in this outbreak, all linked through a single transmission chain to 68 M; 37 cases died . In South Korea, the national health insurance system provides for relatively low cost medical care, defraying some Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: his way to China where he was located, isolated and cared for in China . No contacts became ill. The outbreak was brought under control in late July/ early August after improved IPC measures were employed, strong contact tracing monitoring and quarantine, expanded laboratory testing, hospitals were better secured, specialized personnel were dispatched to manage cases and international cooperation increased . A review of public data showed that, as for MERS in the KSA, older age and the presence of underlying disease were significantly associated with a fatal outcome in South Korea. Even though R 0 is <1, super-spreading events", "Title: Natural Killer Cells Promote Early CD8 T Cell Responses against Cytomegalovirus\nPassage: influenza, or SARS. Title: IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection\nPassage: for innate immune effectors including natural killer cells, which provide short-term control of viral replication prior to T cell activation . NK cells become activated following the loss of inhibitory signals coupled with positive activating signals resulting in direct or indirect target cell lysis . NK cells are vital in limiting influenza viral replication as depletion of NK cells dramatically increases morbidity and mortality in hamsters and mice , and in humans severe infections with the 2009 pandemic H1N1 virus positively correlated with reduced numbers of NK cells in the lungs . Studies have indicated that the natural cytotoxicity receptors Title: Innate Immune Sensing and Response to Influenza", "Passage: NK cells possess unique natural cytotoxicity receptors such as NCR1 in mice, and NKp30, NKp44, and NKp46 in humans, involved in recognition of viral-and tumor-associated molecules and activation of NK cells . Influenza virus productively infects human NK cells in vitro . In mouse models of influenza virus infection, there is a substantial increase in the population of activated NK cells expressing CD107a and IFN-c in the lungs, which can lyse influenza virus-infected cells through granzyme B and perforin, and contribute to the virus control . Accordingly, NK cell-depletion or defects in NK cell activity resulted in delayed virus clearance Title: IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection", "Passage: NKp44 and NKp46, which recognize hemagglutinin proteins of several different influenza strains is one mechanism used by NK cells to protect against lethal viral challenge . Secondarily, NK cells also aid in viral clearance indirectly through the production and secretion of cytokines which both amplifies local inflammation and recruits antigen-specific CD8 T cells to sites of inflammation . Implicit in both of these functions is the ability of NK cells to accumulate within the respiratory tract to contact infected cells and provide a source of chemotactic signals to recruit recently activated CD8 T cells.", "Title: The 1918 Influenza Pandemic: Looking Back, Looking Forward\nPassage: If again confronted with a deadly flu pandemic, we would be in a better place than we were in 1918 because of the availability of drugs, vaccines, and antibiotics and the general improvements in health and nutrition. There are high hopes for the development of universal vaccines, but we need to keep in mind that influenza is a rapidly evolving virus that has a large and diverse animal reservoir and presumably many tricks in store. We can only anticipate another hundred years of very active, and always surprising, influenza research. Title: Lessons learned from the 1918\u20131919 influenza pandemic", "Passage: The issue of vaccination was not available until 1931, when a viral growth in embryonated hens' eggs was discovered, and in the 1940s, the US military developed the fi rst approved inactivated vaccines for infl uenza, which were used in the Second World War with limited success. Vaccination is the best defense against the infl uenza if the right strain is predicted, and if there are no mutations after the administration of the vaccine. In the 1957 and 1968, infl uenza vaccination programs were credited with the reduction of the severity of both pandemics. The 1976 swine fl u scare Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: proceeding toward pandemicity. We have little understanding of the risks posed by such IAVs. For example, the 2009 pandemic virus contained gene segments derived from the 1918 pandemic virus, which had been transmitted to pigs in 1918, and had gone on to circulate in pigs over the past century . Are any, or all, swine influenza viruses potential threats to humans? What about IAVs that circulate in horses or dogs? A panzootic equine influenza virus has switched hosts to cause a canine panzootic ; are humans also at risk of future pandemics arising from similar mammalian host-switching events? And, what Title: It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919", "Passage: better general health and immunity. Furthermore, in 1918 and 1919, physicians and nurses almost had nothing in their hands to help individuals who were infected by influenza viruses. Today, although we still do not have very effective, powerful, and practical anti-influenza drugs available, we at least have some improved, useful, and helpful anti-viral drugs like zanamivir, and effective, convenient anti-cold medicines like Tylenol or Advil. We do not have a universal vaccine to prevent all influenza virus infections, but we can make effective vaccines to a specific influenza virus strain in a short time. Actually, in the United States of", "Title: New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences\nPassage: In contrast with the MBFV and TBFV groups, the NKV SL group remains poorly described. Based on the phylogenetic and TMRCA data, viruses within this group have been introduced to the NW on at least two separate occasions and these introductions may have occurred thousands of years ago. Estimations for the time of divergence between these OW and NW NKV SL ranged between 4000 to 14000 years ago . Despite the recognised large errors in TMRCA estimates, they all pre-date, by thousands of years, the recognised commercial trading period across the Atlantic Ocean that commenced 400-500 years ago. Therefore, viruses Title: Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool", "Passage: scaffolds . Given the large genomes of NCLDVs, hits to this class of viruses were reanalyzed with the profile hidden Markov model-based algorithm HHblits. PCR and Sanger sequencing were used to confirm the presence of novel viral-like sequences in our samples. doi:10.1371/journal.pone.0060595.g001 of higher eukaryotes . NCLDV include the families Poxviridae, Phycodnaviridae, Iridoviridae and Mimiviridae . We found hits to NCLDV in all libraries included in this report . Although five conserved ortholog gene clusters have been identified within the genomes of all NCLDV , none of these were found in our bioinformatics analyses. Given that phycodnaviruses and mimiviruses have Title: New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences", "Passage: On the other hand, the TMRCA estimates for the other 6 NW lineages suggest that these viruses potentially could have been introduced to the NW more than one thousand years before the initiation of historic commercial and slave trading across the Atlantic Ocean ; ILHV group ; SLEV Phylogeny of Flaviviruses ; CPCV ; NW bat NKV SL and NW rodent NKV SL . These estimate are less accurate, due to the relatively short term calibration date we have used for YFV as reference, and could be thousands or even more years in the past. All apparent virus migrations during Title: New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences\nPassage: during the \"ancient period\", which in the case of the NKV SL are not vectored by arthropods.", "Title: The Trojan Chicken Study, Minnesota\nPassage: Some of our study findings were unanticipated. We expected contamination proportions to vary by age, gender, and role because we expected these factors to affect the amount of contact with birds and handwashing behavior. However the rates did not vary by these variables. This finding could be due to the study's limited power to detect such differences. If the differences between those exposed and those unexposed were statistically significant , they might be consistent with studies that suggest that animal handlers practice better hygiene compared to nonhandlers in the same environment. Alternatively, animal handlers may engage in other behavior that Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: A classic human study found that, in donors lacking neutralizing antibodies, pre-existing cytotoxic T-cell levels against influenza correlated with reduced virus shedding but not reduced symptoms after influenza virus challenge . Epidemiological studies of the 1957 pandemic, an H1N1 to H2N2 shift, suggested cross-protection, but these studies were too small for statistical significance or lacked laboratory confirmation of self-reported symptoms . A human challenge study found a correlation of CD4 memory with reduced illness duration, viral shedding, and symptom severity . Title: Suffering a Loss Is Good Fortune: Myth or Reality?", "Passage: There were four potential limitations to our study. First, we only conducted a cross-sectional study in Study 3, whereas it would be preferable to measure Chikui likelihood earlier and then track the material and mental benefit of our participants years later. In the absence of a longitudinal study, our findings are suggestive but do not prove causality, and the following two questions therefore remain unaddressed: we are unable to confirm whether the correlation found in Study 2 means that it is the belief that boosts both financial and psychological well-being, rather than the reverse . Only a longitudinal study can Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: of a certain human leukocyte antigen -B family react to this peptide, but not all donors. Thus, this marker could not be used alone for screening purposes but perhaps as part of a group of markers. We describe it as an interesting case study and proof-of-concept for this type of testing. ). One hundred thirty-seven donor sera were tested; each circle represents 1 donor. The solid red circles represent values above a 3% threshold considered positive. Open black circles are considered negative. Values <0 reflect more binding to untransfected cells than to transfected cells , which is presumably nonspecific.", "Title: Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes\nPassage: The most striking of the linked hotspots is the RL11 region , where strong linkage is found between thirteen genes. Although the high degree of linkage in this region has previously been noted , our whole genome analyses reveal this is the only region of the HCMV genome showing any evidence of a consistent evolutionary history . These uniquely large haplotypes in the HCMV genome could reflect immune pressure for co-segregation of antigenic alleles at multiple loci into nonoverlapping combinations of antigens to avoid cross-immunity, a phenomenon which has been shown to occur in some bacterial pathogens . However, the Title: Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes", "Passage: To compare phylogenetic histories of different gene loci, the diversity of phylogenetic signals recorded in HCMV genomes was explored by building a matrix of posterior probability supports of tree bipartitions observed in each gene's MCMC sample of trees . Linkage between neighboring genes was identified as tracks of genes with shared high PP for the same bipartition. This method enables the recognition of similar clusters of strains along the genome, signing their recent history of common descent. In particular this approach does not require that all sequences share the history of descent across loci and hence allows identification of haplotypes Title: Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya", "Passage: A cost-distance function to account for factors that may either impede or facilitate travel was also used to delineate landmark catchment areas. Given the gently undulating topography of the study area, it was assumed that ease and speed of travel between compounds and relevant landmarks is determined either by the presence of roads or by the presence of rivers . Roads and rivers in the study area were digitized using highresolution Quickbird satellite multispectral imagery at 2\u00b78 m resolution sharpened with a 60 cm resolution panchromatic image. Roads were classified into four categories: tarred roads where the likely maximum speed Title: Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting", "Passage: Municipality and district were also provided, allowing cross checking for 66 duplicate neighbourhood names and ensure continuity. In addition, searches were made online for 67 local schools, churches, news stories and community groups to cross check locations. Many addresses 68 listed geographic features such as landmarks or road names. Where possible, Google satellite imagery 69 were examined for these features and/or evidence of dwellings. 70", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: The role of a declaration of a PHEIC in managing a serious outbreak has been questioned in the light of Ebola in West Africa and in the Democratic Republic of Congo and has been challenged again with this outbreak. The binary nature of a PHEIC declaration and the specificity of the three defined criteria for a PHEIC have caused difficulty for Emergency Committees in considering whether a given event should be a PHEIC. The lack of a clear understanding of what a PHEIC declaration is meant to achieve adds to the Emergency Committee's difficulties, as does the relative paucity of Title: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management", "Passage: obtained . However, the rate of spread of the virus and the uncertainties surrounding the entire situation has led the World Health Organization on 30 January 2019 to declare the Coronavirus outbreak a 'Global Public Health Emergency'. WHO determined, however, not to declare the outbreak a 'Public Health Emergency of International Concern' which is a higher level of declaration. A PHEIC is defined as \"an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response\" whose scope may include: serious, sudden, unusual Title: Eliminate now: seven critical actions required to accelerate elimination of Plasmodium falciparum malaria in the Greater Mekong Subregion", "Passage: The PHEIC mechanism as developed and implemented by the WHO allows the organization to formally declare that a situation is \"an extraordinary public health event which is determined to constitute a public health risk to other countries through the international spread of disease; and to potentially require a coordinated international response. \" Zika virus disease was declared a PHEIC in February 2016 on the basis of limited epidemiological data . It is somewhat difficult to reconcile this action with the current situation in the GMS; MDR-P. falciparum certainly poses an equally grave international threat. There is also somewhat of a Title: Eliminate now: seven critical actions required to accelerate elimination of Plasmodium falciparum malaria in the Greater Mekong Subregion", "Passage: There should be no doubt that the response to MDR-P. falciparum needs to be funded, approached, and managed as an emergency. If the current stringent criteria necessary to declare a PHEIC are not met by the MDR-P. falciparum threat, we suggest an alternative categorization should be created to elevate such 'slow-motion' emergencies to the proper level of global attention: perhaps a 'Category II PHEIC'? The elevation of MDR-P. falciparum to a PHEIC, or creation of an additional PHEIC classification to cover situations such as AR, will require member states to actively work with WHO in lobbying for these changes.", "Title: Viral vector-based influenza vaccines\nPassage: one single study, cross-reactive cellular immune responses against A viruses were observed after vaccination with a NDV-H5 construct. 168 The immunogenicity of recombinant NDV expressing the HA and NA genes of influenza virus A/Vietnam/1203/04 was tested in non-human primates. Both constructs induced VN and local IgA antibody responses and afforded protection from A challenge infection. 169, 170 Small numbers of clinical trials have been performed with NDV, which showed that the vector is well tolerated. Title: Viral vector-based influenza vaccines", "Passage: The first study using NDV as a vaccine vector for influenza was NDV-H1, that expressed the HA gene of influenza virus A/ WSN/1933. Complete protection of mice against homologous challenge infection was achieved, demonstrating that NDV can be used as an influenza vaccine vector. 148 Consequently, a recombinant NDV expressing HA genes of A viruses has been licensed as a poultry vaccine in some countries and was shown to have a protective effect against challenge infection with A viruses in chickens and ducks in various studies. The NDV based A vaccine offered only partial cross-clade protection, but was immunogenic in Title: Virus-Vectored Influenza Virus Vaccines", "Passage: NDV has also been explored as a vaccine vector for humans. Two NHP studies assessed the immunogenicity and efficacy of an rNDV expressing the HA or NA of A/Vietnam/1203/2004 . Intranasal and intratracheal delivery of the rNDV-HA or rNDV-NA vaccines induced both serum and mucosal antibody responses and protected from HPAIV challenge . NDV has limited clinical data; however, phase I and phase I/II clinical trials have shown that the NDV vector is well-tolerated, even at high doses delivered intravenously . While these results are promising, additional studies are needed to advance NDV as a human vaccine vector for influenza. Title: Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses\nPassage: effectively increased the CD8 + T cell response after NDV-Gag prime, whereas this increase was not seen at a similar level after the boost with the RABV-based vaccine vector.", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: severe forms of HFRS and HCPS have begun to achieve sufficient mass as to induce, through PAMP-PRR interactions and other means, the expression of proinflammatory cytokines . For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed, and yet it is often not appreciated that the expected preferential tissue tropism of HFRS-associated viruses and their HCPS-associated counterparts for the renal and pulmonary beds, respectively, is not as one would predict through the manifestations of the two diseases. Title: Health-related quality of life in intensive care survivors: Associations with social support, comorbidity, and pain interference", "Passage: calculated by summing the scores of the four provisions . The revised SPS has been shown to be valid and reliable for use with older adults living in Norway , and the original SPS has been used in studies of hospital nurses , pregnant women, first time mothers , and schoolteachers . The primary differences between the original and revised SPS are the decrease from six to four provisions, respectively, and a change in total score from a maximum of 96 in the original to 64 in the revised version. There are no cut off value to this instrument . Title: High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress", "Passage: ability of bats to survive at these temperatures. This in turn may impact the bat's lifespan and pathogen-host equilibrium as HSPs are involved in both processes ). The evolutionary conserved function of HSP's does not appear to be altered, merely the regulation of expression and intrinsic availability. Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: renal replacement therapy should be applied for those critical HFRS patients, especially when they have a complication, such as multi-organ injury pulmonary edema, or cerebropathy . Treatment of patients with HCPS should also be performed in the ICU with continuous cardiac monitoring and respiratory support. The palliative treatments for HCPS usually include mechanical ventilation, extracorporeal membrane oxygenation, and hemofiltration .", "Title: Lessons learned from the 1918\u20131919 influenza pandemic\nPassage: Those who had suffered from the earlier spring infl uenza generally suffered less discomfort in the second wave which would occur in the early summer of 1918 in Europe, affecting the outcome of the war. The third and most deadly wave of the infl uenza would occur later that year in the late fall. Despite the obvious differences between the strains in each wave, it is suggested that the more virulent form of infl uenza was genetically derived from the spring infl uenza . The antigenic composition of the 1918 virus is related to the H1N1 viral group. Phylogenetic studies Title: Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People\u2019s Republic of China", "Passage: The number of cases was much higher in the second wave, including both more severe and non-severe cases compared with both the first and third wave. This increase may have been due to early and increased recognition of cases, and further spread of the virus to other parts of China. Non-severe cases may have been more likely to be identified in the second wave because of the two week enhanced surveillance for all ILI case-patients in the counties or districts where H7N9 cases were detected . Some counties or districts detected a higher number of non-severe cases through this mechanism Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: The second wave of the 1918 pandemic differed from the first in that much higher morbidity and mortality rates were reported, with the majority of all fatalities associated with the pandemic occurring during this wave . Ultimately, the pandemic would result in an estimated 500 million infections worldwide and a case fatality rate > 2.5%, more than 25 times higher than any other pandemic . As a testament to the severity of this second wave, during the fall of 1918, the first 4-5 pages of Spanish newspapers were filled with obituaries of those who had succumbed to the pandemic virus Title: Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People\u2019s Republic of China", "Passage: During the third wave, there were 219 cases and 98 deaths in mainland China . The peak in reported cases occurred between January and February 2015 . The number of cases was less compared to the second wave. Men accounted for 69% of reported cases during the third wave which was similar to the previous two waves . The median age of case-patients reported in the third wave was 56 years which was slightly lower compared to the first wave , and was similar to the second wave . The CFP of cases increased from 33% to 42% and 45%", "Title: A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014\nPassage: The H7N9 influenza virus is spreading, evolving and becoming widespread among chickens in China 6 . Fortunately, the virus has not completely obtained the ability for human-like receptor binding and human-to-human transmission. Moreover, the H7N9 virus still mainly originates and evolves in avian species; therefore, it is possible to intercept the interspecies transmission by controlling or standardizing live poultry trade. Additionally, we should persistent in monitoring the gene evolution of the H7N9 virus isolated from humans and avian species and should optimise diagnostic tools, develop antiviral drugs and spread effective combination therapies for H7N9 infections. Title: Epidemiological, clinical, and virologic features of two family clusters of avian influenza A (H7N9) virus infections in Southeast China", "Passage: In summary, the results of this study demonstrate that one family cluster was infected with H7N9 through exposure to the same live poultry or contaminated environments, and the other was more likely to be transmitted through the human-to-human route. Until now, there has been no stable and effective human-to-human transmission of H7N9 viruses; however, increasing evidence shows that the H7N9 virus has become better adapted to mammalian infections 3, 45, 46 . Therefore, it is of great importance to strengthen the surveillance of the H7N9 virus among poultry and humans, confirm the source of infections, trace and investigate close contacts Title: Influenza A H5N1 and H7N9 in China: A spatial risk analysis", "Passage: We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures. We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections. PLOS Introduction A zoonotic avian influenza virus of subtype H5N1 emerged in humans in Hong Kong in 1997. The virus has since spread across Asia, Africa and Europe, and has infected over 854 humans and caused over 450 deaths . In 2013 a new subtype H7N9 emerged in humans Title: A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014", "Passage: a novel genotype found in chickens that then reassorted with other H9 or H7 virus in birds before being transmitted to humans. This finding suggested that the reassortment with other subtype viruses in avians is still the major evolutionary path of the H7N9 virus; then, sensitive people would be infected after exposure to the mutated viruses. Hence, diverse H7N9 genotypes or reassortants were consecutively isolated in humans. To standardize or close the live poultry trade would be the most efficient way to prevent and control the human-avian influenza virus infection disease.", "Title: Estimates of the Demand for Mechanical Ventilation in the United States During an Influenza Pandemic\nPassage: We present in Table 3 the calculated health outcomes , the number of ventilators needed , and number of deaths averted. The number of ventilators needed at peak range from approximately 7000 to 11 000 to approximately 35 000 to 60 500 . The total number of ventilator-related averted deaths range from approximately 35 000 to 55 000 to approximately 178 000 to 308 000 . Of note is that, for a given level of severity, there is some overlap in the ranges of estimates produced by the 2 CAR. For example, for high severity clinical attack scenarios, the number Title: Estimates of the Demand for Mechanical Ventilation in the United States During an Influenza Pandemic", "Passage: The estimates of ventilators derived from this analysis based on several pandemic scenarios can guide planning for a future pandemic. Stockpiling ventilators can be informed by these estimates and should include assumptions about ventilators that are currently held in Federal and state stockpiles as well as those located in US hospitals. Title: Estimates of the Demand for Mechanical Ventilation in the United States During an Influenza Pandemic\nPassage: over time is that our estimates of demand for ventilators at peak are approximately 1.6-2.3 times smaller than if we used the standardized, 20% or 30%, attack rate curves . We also conducted sensitivity analyses to test the impact of assuming that peak demand was a larger percentage of total ventilator demand . Title: Estimates of the Demand for Mechanical Ventilation in the United States During an Influenza Pandemic", "Passage: assumed 10 days ventilator use per ventilated patient, 13% of total ventilator demand will occur at peak, and a 33.7% weighted average mortality risk while on a ventilator. At peak, for a 20% CAR, low severity scenario, an additional 7000 to 11 000 ventilators will be needed, averting a pandemic total of 35 000 to 55 000 deaths. A 30% CAR, high severity scenario, will need approximately 35 000 to 60 500 additional ventilators, averting a pandemic total 178 000 to 308 000 deaths. Estimates of deaths averted may not be realized because successful ventilation also depends on sufficient numbers", "Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome\nPassage: Next, we determined the subcellular localization of the SARS-CoV 3a protein using confocal microscopy. When the SARS-CoV Cell-free supernatants were collected at 24 h or 6 h post-infection or stimulation, and analyzed for IL-1\u03b2 by ELISA. Data are representative of at least three independent experiments, and indicate the mean \u00b1 SD; * * P < 0.01 and * * * P < 0.001. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Abstract: Nod-like receptor family, pyrin domain-containing 3 regulates the secretion of proinflammatory cytokines interleukin 1 beta and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus 2B proteins stimulate IL-1\u03b2 secretion following activation of the NLRP3 inflammasome. However, the mechanism by which severe acute respiratory syndrome coronavirus activates the NLRP3 inflammasome remains unknown. Here, we provide direct evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages. SARS-CoV 3a was sufficient to cause the NLRP3 inflammasome activation. The ion channel activity of the 3a protein was essential for 3a-mediated IL-1\u03b2 secretion. While cells uninfected or infected Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: . Although cells expressing the ion channel activity-loss mutants 3a-CS or V25F uniformly expressed NLRP3 throughout the cytoplasm, it was redistributed to the perinuclear region in SARS-CoV 3a-or E-expressing cells . Together, these data provide evidence that the ion channel activity of the SARS-CoV 3a protein is essential for triggering the NLRP3 inflammasome. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Finally, we investigated the mechanism by which SARS-CoV 3a triggers NLRP3 inflammasome activation. A previous study showed that the 3a protein of SARS-CoV acts as a K + channel . In addition, K + efflux is a well-known activator of the NLRP3 inflammasome . These observations prompted us to examine whether K + efflux is required for 3a-mediated IL-1\u03b2 secretion. To this end, BMMs in K + -rich medium were infected with influenza A virus or lentiviruses expressing the SARS-CoV E or 3a proteins. In agreement with a previous result , we found that IL-1\u03b2 secretion caused by influenza virus", "Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: of this manuscript. Title: Australian public health policy in 2003 \u2013 2004\nPassage: marveled at the value of the Abelson report, described in more detail below. Title: Australian public health policy in 2003 \u2013 2004", "Passage: The release in 2003 of the report \"Returns on Investments in Public Health: an epidemiological and economic analysis\" , may have a significant impact in subsequent years. Commissioned several years earlier by the Population Health Division of the Department of Health and Ageing , the report experienced a relatively low profile until Derek Wanless visited from the UK. Having chaired a review that contributed to a significant budgetary increase for the NHS, Wanless had been commissioned by the British Treasury to examine prevention across government. In September 2003, at a meeting in Canberra with senior officials across key agencies, Wanless Title: A bibliometric analysis of IL-35 research from 2009 to 2018\nPassage: further analysis.", "Title: Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients\nPassage: There was a significant difference in clinical specimen distribution between the two groups as shown in Table 1 . The proportion of blood and urine specimens taken from the SBA group was higher than that of the SAA group , while the proportion of respiratory secretions , body fluid specimens , stool, and other specimens sampled from the SBA group were lower than those of the SAA group with significance . Title: Current progress in innovative engineered antibodies\nPassage: trials is SAB-301 , a polyclonal mixture of human IgGs targeting middle east respiratory virus . Title: Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients", "Passage: The microbiological results suggested that the culture positive rate in the SBA group was higher than that of the SAA group , but there was no significant difference in the proportion of polymicrobial results between the two groups . Title: Chemical and Biological Mechanisms of Pathogen Reduction Technologies\nPassage: been required by regulatory agencies nor performed; toxicology studies have only been carried out with the degradation product, S-300. However, because S-303 is a nucleic acid alkylating agent, the parent compound would be expected to be genotoxic. Nevertheless, no adverse effects were observed when five times the standard dose was used to prepare RBCs that were subsequently transfused into rat and dog models .", "Title: The Gut, Its Microbiome, and Hypertension\nPassage: Gut epithelium has a vast surface area, necessary for efficient absorption and secretion. This large surface area presents a challenge to maintain its epithelial barrier function and it is estimated that \u223c70% of the body's immune cells reside in the gut, constituting the \"gut associated lymphatic tissue\" . The GALT moderates the continuous interactions of the bacterial communities and their byproducts with the gut . The gut microbiome interacts with the immune system of the host to \"educate\" it, as germ-free mice have a defective immune system . This \"education\", begins perinatally and continues until about 3 years of age Title: Oral administration of inactivated porcine epidemic diarrhea virus activate DCs in porcine Peyer\u2019s patches", "Passage: Gut is the major immune organ of the body and the intestinal mucosa is thought to be the primary site for performing local-specific immune responses. Gut associated lymphoid tissue , consists of isolated or aggregated lymphoid follicles forming Peyer's patches , is considered to be the key inductive tissues for the mucosal immune system . PPs are known as the immune sensors of the intestine because of their ability to transport luminal antigens and bacteria into organized lymphoid tissues within the intestinal mucosa . PPs contain too many immunocompetent cells that are required for the generation of an immune response. Title: Cytokines IL-17 and IL-22 in the host response to infection", "Passage: Leukocytes constitute the second largest class of cells found within the intestine, second only to epithelial cells . Within the intestinal mucosa, leukocyte types are segregated into two distinct anatomic areas: the lamina propria and the epithelium . The LP harbors adaptive immune cells such as T cells and B cells, as well as innate immune cells, including dendritic cells , macrophages and eosinophils. In contrast, specific subsets of cells called intraepithelial lymphocytes are found associated with the epithelial layer, in particular at the basement membrane between enterocytes . Gut IELs are almost exclusively T cells, as originally estimated based Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: The mucosal surface is the first location where the host and its environment contact; therefore, it has a prominent defense mechanism against pathogens. Mucosal route vaccine delivery systems are based on mucosa-associated lymphoid tissue , which is found on various mucosal surface areas. MALT is a lymphoid tissue in the nasopharynx, pharynx, salivary gland, and upper respiratory tract, which are known as nasal-associated lymphoid tissues . MALT is also found in the broncho epithelium and lower respiratory tract , gastrointestinal tract and genital tract. MALT is composed of epithelial cells identified as follicle-associated epithelium or microfold cells that act as", "Title: Passive Broad-Spectrum Influenza Immunoprophylaxis\nPassage: influenza. Prophylaxis could protect against both morbidity and mortality rates by lowering the number of cases. Effective passive immunity is important to provide coverage during the first wave or six-month risk period of the pandemic whilst an effective vaccine is developed for the identified virus to induce active immunity. Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Influenza vaccination is the primary method for preventing influenza and reducing the risk of severe outcomes. In the U.S., the Advisory Committee on Immunization Practices recommends annual influenza vaccination for all persons aged 6 months and older and prioritizes those at higher risk for influenza complications . High-risk groups include adults aged > 65 years , children aged < 5 years , pregnant women , persons with certain chronic medical conditions, Native Americans/Alaska Natives, 1 and residents of nursing homes and other long-term care facilities . Studies have specifically highlighted that those with chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic Title: Passive Broad-Spectrum Influenza Immunoprophylaxis", "Passage: Effective passive broad-spectrum protection during the early phase of an epidemic could provide a barricade to virus exposure, especially during the interval between virus identification and active vaccine-induced immunity. As a consequence, early intervention with passive prophylaxis may revolutionize control options for influenza with potential impact on seasonal and pandemic influenza preparedness. Influenza A and influenza B viruses cause seasonal disease in the winter months of both hemispheres with 250,000-500,000 deaths each year . Although the natural animal reservoir for influenza A viruses is aquatic shorebirds, high pathogenicity avian influenza viruses 2 Influenza Research and Treatment have recently emerged with Title: Augmented Lung Inflammation Protects against Influenza A Pneumonia", "Passage: Epidemic respiratory infections, as previously observed with influenza and SARS , result in high mortality, sometimes before the pathogen is identified, and often without effective post-exposure treatment options. Seasonal influenza, though the case-mortality rate is lower, still kills ten of thousands of Americans annually and clinicians are faced with the problems of ineffective vaccine strategies and declining effectiveness of neuraminidase inhibitors . In such situations, rapidly dispersed, broad protection would be highly advantageous.", "Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide\nPassage: The three-dimensional structure of NTCP protein has not been well characterized and the number of transmembrane domains is controversial at present. Several groups have predicted that NTCP has 7-9 transmembrane domains and that the C-terminus of NTCP is located in the cytoplasm . We found that our 9A8 mAb recognizes amino acids 317-326 of NTCP on intact cells without membrane permeabilization, implying that this epitope is possibly exposed to the extracellular space. More precise structural biological studies should be carried out to elucidate the topology of the NTCP protein. Title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", "Passage: Stieger, 2011) . NTCP is a multiple transmembrane glycoprotein presumed to span the cellular membrane up to 10 times with small extracellular loops . It is mainly expressed in the liver , consistent with the liver tropism of HBV and HDV. NTCP localizes to the sinusoidal plasma membrane of hepatocytes , a location that fits well with its receptor role for blood-borne HBV and HDV. Whereas HBV first attaches to hepatocytes mainly through heparan sulfate , our data demonstrate that the interaction between NTCP and L protein of HBV is highly specific, and NTCP is crucial for productive viral entry Title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", "Passage: and subsequently examined with anti-C9 mAb 1D4 by Western blotting. For total NTCP expression, the same transfected cells expressing wild-type or mutant NTCPs were lysed with 1\u00d7 RIPA buffer and treated with PNGase F. Each sample containing same amount of total cellular protein were loaded for SDS-PAGE followed by Western blotting analysis with mAb 1D4 that recognizes the C9 tag fused at the C-terminus of NTCPs. Title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus\nPassage: with NTCP were shown by the kinetic analyses of several markers of viral infections, in particular the quantification of newly synthesized viral replicative intermediates. Moreover, the NTCP-rendered infections were blocked by known entry inhibitors. NTCP residues 157 to 165 were identified to be critical for pre-S1 binding and viral infections. These data clearly demonstrate that NTCP is a functional receptor for both HBV and HDV.", "Title: Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future\nPassage: Rotaviruses are non-enveloped viruses with a three layered capsid that contains 11 segments of double-stranded RNA . The rotavirus genome encodes six structural proteins, designated as VP1-VP4, VP6 and VP7, and five or six nonstructural proteins, designated as NSP1-NSP5/6. The VP7 protein forms the outer layer of the capsid. The VP4 spike proteins project outward from the capsid. The outer capsid VP7 and VP4 proteins are antigenically significant, eliciting neutralizing antibodies, and form the basis of the currently licensed rotavirus vaccines . The VP6 constitutes the middle capsid layer, whilst VP2 is the inner core protein. The VP1 is the Title: The Eukaryotic Translation Initiation Factor 4F Complex Restricts Rotavirus Infection via Regulating the Expression of IRF1 and IRF7", "Passage: The genome of rotavirus contains 11 segments encoding 12 proteins including six structural and six non-structural proteins . Among the structural proteins, as a spike protein, rotavirus VP4 plays an essential role in both viral entry and exit . VP4 was also demonstrated to be of importance in viral attachment and internalization , which is often used for the development of rotavirus vaccines . VP4 contains two subunits including a C-terminal subunit VP5* and a N-terminal subunit VP8*, and both VP5* and VP8* help virus entry by interacting with several putative partners and cell surface receptors . The rotavirus genome Title: Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFN\u03b1 Response", "Passage: is also observed during infection. The nonstructural proteins are involved in viral replication, morphogenesis and assembly, but they are not expressed by nonreplicating virus and are not part of the infectious virion . Title: Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFN\u03b1 Response\nPassage: and the inhibition of NFkB activation, by a viral nonstructural protein, NSP1 .", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Once a contagious infectious disease has been identified, the EMICT must consider four Title: Ebola virus disease and critical illness\nPassage: While it may be advisable to concentrate or regionalize care for patients with EVD in specific hospitals, any health centre should be prepared to safely take a focused and relevant history from a patient with an infectious syndrome, and to mobilize the appropriate local and regional response. Many hospitals, even if not EVD referral centers, may be asked to care for patients until initial blood Ebola RT-PCR results are known. Therefore, it is essential that hospital staff are well trained and familiar with recommended IPC practices . It is ideal to have an on-call inter-professional team who have undergone training Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management", "Passage: other personal protection as established by the EMICT. Title: Ebola virus disease and critical illness\nPassage: Although this EVD outbreak narrowed some knowledge gaps, pathophysiology and the immunological response to acute infection and convalescence is still minimally characterized. Access to rapid point-of-care EVD diagnostic capacity to differentiate between other common febrile illnesses is critical because the early presentation of EVD has a broad differential diagnosis . Laboratory testing to identify prognostic indicators could help guide clinical care. Evaluation of specific antiviral therapies is critical as is evaluation of commonly used treatments for which there is still very limited evidence . The safety and functionality of PPE must be improved. Standardized, easy-to-use clinical charting and human resources", "Title: The Failure of R (0)\nPassage: In this paper, we outline the problems with R 0 and examine a number of alternatives that have been proposed. We include a worked example of malaria to demonstrate the many different results that the various methods give for the same model. Finally, we survey some of the recent uses of R 0 in the literature. The number of articles that use R 0 likely numbers in the tens of thousands, so an exhaustive review is not feasible. We have restricted ourselves to articles published since 2005 and which include interesting or novel explorations of R 0 . Title: Inferring R(0) in emerging epidemics\u2014the effect of common population structure is small\nPassage: extreme values of R 0 . Even though this is clearly beyond the scope of this study, obtaining more information on such extreme values is a worthwhile objective for future work. Title: The Failure of R (0)", "Passage: Breban et al. showed that two individual-level models having exactly the same expectations of the corresponding population-level variables may yield different R 0 values. They showed that obtaining R 0 from empirical contact-tracing data collected by epidemiologists and using this R 0 as a threshold parameter for a population-level model could produce misleading estimates of the infectiousness of the pathogen, the severity of an outbreak, and the strength of the medical and/or behavioural interventions necessary for control. Thus, measuring R 0 through contact tracing may not be a useful measure for determining the strength of the necessary control interventions. Title: The Failure of R (0)\nPassage: illustrates the wide variety of values that are presented as being \"the\" R 0 value for a specific disease.", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's Title: Why language matters: insights and challenges in applying a social determination of health approach in a North-South collaborative research program", "Passage: A comparative analysis of the positive and negative effects of agro-ecological and conventional production systems is underway to consider policy options to promote health equity by ensuring that such factors are considered in food-related decision-making. There are extensive measurement challenges in doing this. Title: Why language matters: insights and challenges in applying a social determination of health approach in a North-South collaborative research program", "Passage: We have successfully demonstrated the INSOC index as a more sensitive measurement tool for analyzing social gradients of vulnerability. As well, a computerized system for rapid notification to increase the efficiency and effectiveness of health system performance has been introducedwith the intention of building this as part of an intersectoral integrated system for monitoring additional elements to be addressed in control and prevention actions. The effectiveness, albeit limited, of community prevention and control activities has been documented, setting the stage for a more comprehensive analysis of options for intervention that can provide stronger prospects for reducing exposure to dengue. Title: Why language matters: insights and challenges in applying a social determination of health approach in a North-South collaborative research program", "Passage: Empirical research conducted with survey research methods demonstrated burnout in medical staff, associated with their modes of living and the managerial decisions that affect their work life.", "Title: Viral vector-based influenza vaccines\nPassage: Several different vaccine formulations are available: trivalent or quadrivalent inactivated virus vaccines or live attenuated influenza virus vaccines . Most vaccines are produced in embryonated chicken eggs, but vaccines produced in mammalian or insect cells are also available. Inactivated vaccines are administered intramuscularly or sometimes intradermally and predominantly aim at the induction of serum antibody responses against the viral hemagglutinin and neuraminidase to a lesser extent. Protection from disease is mainly mediated by virus neutralizing antibodies against HA, but NA-specific antibodies also contribute to protective immunity. 1 Currently licensed LAIV are administered locally via nasal spray. Viruses are attenuated by Title: Virus-Vectored Influenza Virus Vaccines", "Passage: The general types of influenza vaccines available in the United States are trivalent inactivated influenza vaccine , quadrivalent influenza vaccine , and live attenuated influenza vaccine . There are three types of inactivated vaccines that include whole virus inactivated, split virus inactivated, and subunit vaccines. In split virus vaccines, the virus is disrupted by a detergent. In subunit vaccines, HA and NA have been further purified by removal of other viral components. TIV is administered intramuscularly and contains three or four inactivated viruses, i.e., two type A strains and one or two type B strains. TIV efficacy is measured by Title: Current and Novel Approaches in Influenza Management", "Passage: Three types of vaccines against influenza are currently used worldwide including inactivated influenza vaccine , live-attenuated influenza vaccine and influenza virus subunit vaccine: each of which has its own advantages and drawbacks. IIV is formulated with replication-incompetent virus, due to whole pathogen inactivation usually achieved by formaldehyde treatment or split virion vaccines generated by disruption of the viral membrane . Intramuscular administration of the IIV has been shown to induce both local and systemic immunity . However, to maintain the antibody titers, booster vaccinations are required. Additional considerations on the vaccine efficacy were raised following metadata analysis suggesting only 40% Title: Reverse Genetics Approaches for the Development of Influenza Vaccines", "Passage: Killed virus vaccines or IIV are generally administered intramuscularly and can be classified as whole virus vaccines or split vaccines . Whole virus vaccines were the first to be developed. The influenza virus is grown in embryonated chicken eggs, subsequently purified, concentrated and chemically inactivated with formaldehyde . Whole virus vaccines are safe and well tolerated, with an efficacy of 60%-90% in children and adults. On the other hand, the split-virus vaccine exposes all viral proteins and subviral elements upon dissociation of the virions by a nonionic detergent treatment step . Most influenza vaccines in the U.S. and Europe are", "Title: Ad Hoc Influenza Vaccination During Years of Significant Antigenic Drift in a Tropical City With 2 Seasonal Peaks: A Cross-Sectional Survey Among Health Care Practitioners\nPassage: influenza seasons are January to March and June to August, 8 and the government has opted to offer the Northern Hemisphere vaccine once a year in October to December. In early 2015, a heavy flu season occurred due to the newly drifted influenza strain, A H3N2 Switzerland that had not been included in the Northern Hemisphere vaccine. In view of the reduced level of protection as reported elsewhere, 9 the Hong Kong Government decided to place an additional procurement of Southern Hemisphere vaccine that contains the new virus strain. Given the limited supply, the additional dose of vaccine was only Title: Reverse Genetics Approaches for the Development of Influenza Vaccines", "Passage: be generated in embryonated eggs for vaccine manufacturing due to regulations . Nowadays, the vaccine strains must be selected almost 7-9 months ahead of the influenza season in which they will be used. The recommendation for the strains included in the vaccine composition for the Northern Hemisphere is made in February to allow time for the~300 million doses of vaccine to be produced in time for vaccinating people in October/November. This allows for influenza season preparation, which typically peaks sometime between December and March . On the other hand, for the Southern Hemisphere, recommendations are provided in September, and vaccination Title: A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations", "Passage: activity occurs during November to April on the Northern hemisphere and vaccination is usually administered between October and November. Therefore, travellers visiting the opposite hemisphere have to be counselled accordingly and the seasonal influ-enza vaccine also for the Southern hemisphere has to be available as there is year-round influenza activity in tropical and subtropical areas. Title: Improved Global Capacity for Influenza Surveillance", "Passage: Each year, the 5 WHO Collaborating Centers for influenza receive influenza specimens or viral isolates from NICs to analyze for seasonal influenza vaccine strain selection . Using the Northern and Southern Hemisphere vaccine strain selection information packages, we analyzed the change in the number of countries with NICs that shared specimens at the start of the program, compared with those sharing specimens in 2013; this change served as an indication of global contribution to vaccine strain selection. All data were analyzed by using Microsoft Excel .", "Title: Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides\nPassage: To this end follow-up research can focus on further metabolic engineering or on process optimization fermentation which enables in situ recovery] to improve these issues. Title: Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides", "Passage: The constructed galactosylation and rhamnosylation strains were grown on minimal medium with two levels of quercetin. Growth and production were monitored to determine the specific productivities, as shown in Fig. 4 . Again, higher extracellular quercetin concentrations resulted in a fivefold increase in q p . However, no significant difference in productivity was observed between sGAL2 and sGAL3 at 1.5 g/L quercetin, indicating that UDP-galactose formation is as efficient with both GalE homologs and not likely the rate limiting step. With sGAL3, the highest hyperoside productivity and titer were obtained, the latter being 3.5-fold higher compared to sGAL1. Title: Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides", "Passage: To demonstrate the scalability of the developed bioprocess, strain sGAL3 was cultured in a 1-L bioreactor, which also ensures a constant pH set at 6.80 and avoid oxygen limitation. A detailed overview of the consumption of sucrose, growth and hyperoside production is given in Fig. 5 . After a lag-phase, the strain displayed a growth rate of 0.32 \u00b1 0.02 h \u22121 while simultaneously producing hyperoside. The observed specific productivity was comparable to the one obtained on shake flask scale. When nearly all quercetin was converted, hyperoside formation slowed down, which can be explained either by the observed correlation between Title: Addicted to sugar: roles of glycans in the order Mononegavirales", "Passage: Each strategy in the study of glycosylation has advantages and disadvantages. For example, mass spectrometry can yield valuable chemical information but often requires quantities of protein that may be impractical for some viral studies . Cells can be treated with enzyme inhibitors, such as tunicamycin, a chemical that inhibits N-glycan synthesis within the ER, through chemical treatment. However, in addition to blocking glycosylation, tunicamycin may have other undesirable side effects within the cell, such as protein misfolding ). There are also enzymes available for studying glycan composition. Peptide-N-glycosidase F cleaves all N-glycans from proteins. Endoglycosidase H cleaves high-mannose oligosaccharides and", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market to people, we simplified the model as Reservoir-People transmission network model, and R 0 was calculated based on the RP model to assess the transmissibility of the SARS-CoV-2. Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Host resilience to emerging coronaviruses", "Passage: REviEW Jamieson future science group Risk factors for SARS-CoV patients included an older age and male . Immune factors that increased mortality for SARS-CoV were a higher neutrophil count and low T-cell counts . One factor that increased disease for patients infected with SARS-CoV and MERS-CoV was infection with other viruses or bacteria . This is similar to what is seen with many other respiratory infections. A recent study looking at malaria infections in animal models and human patients demonstrated that resilient hosts can be predicted . Clinical studies have started to correlate specific biomarkers with disease outcomes in ARDS Title: Host resilience to emerging coronaviruses", "Passage: higher mortality rate, with 35-50% of diagnosed infections resulting in death . These deadly betacoronavirus viruses existed in animal reservoirs 9, . Recently, other CoVs have been detected in animal populations raising the possibility that we will see a repeat of these types of outbreaks in the near future . Both these zoonotic viruses cause a much more severe disease than what is typically seen for CoVs, making them a global health concern. Both SARS-CoV and MERS-CoV result in severe lung pathology. Many infected patients have acute lung injury , a condition that is diagnosed based on the presence of", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: followed by a sudden explosion of cases in 2007. An estimated 1.3 million people across 13 states were reported to be infected in India , and CHIKV was also widespread in Malaysia, Sri Lanka, and Indonesia . In July-August of 2007, CHIKV was reported in Italy, probably brought in by travelers from CHIKV-prone regions of India, Africa, and Indian Ocean islands such as Mauritius, Madagascar, and Seychelles. Few of the Italian isolates were found to have evolved from the Kerala isolate, which was associated with a A226V shift in E1 gene that represents a successful evolutionary adaptation in the mosquito Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: The 2005-2006 epidemic of CHIKV in La Reunion islands in the Indian Ocean, spurred the discovery of a new vector species, Ae. albopictus . Wrecking over one-third of the island's population, this epidemic peaked its devastation between January and February 2006, when over 46,000 cases came into light every week, including 284 deaths . Ae. albopictus is common in urban areas of the United States and is already flourishing in 36 states, raising grave concerns to the immunologically naive populace of the United States . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: Within a year, the E1-A226V mutation was present in La Reunion Island, and Ae. albopictus apparently vectored the large epidemic infecting 34% of La Reunion Island's population . All of the CHIKV strains isolated from Mayotte carried the E1-A226V mutation, and the mutation was also found in Madagascar in 2007 . The E1-A226V mutation was not present at the beginning of the Indian Ocean Islands outbreak . However, more than 90% of later viral strains found there had incorporated the mutation , indicating a genotype switch during the winter season . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: The E1-A226V mutation also enabled an increase in infectivity of Ae. albopictus when compared to its infectivity of Ae. aegypti , and with several factors taken together, Ae. albopictus has become the new preferred and more lethal vector for CHIKV . In fact, Tsetsarkin et al. found that a Green Fluorescent Protein tagged E1-A226V virus was 100 times more infective to Ae. albopictus than it was to Ae. aegypti . In all the Indian Ocean Islands, Ae. albopictus became the main vector for CHIKV within 1-2 y after CHIKV was introduced to the region .", "Title: Host resilience to emerging coronaviruses\nPassage: Papers of special note have been highlighted as: Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: While well-done reviews in a large number of areas are available, it is important to continue to improve the quality of the overall body of public health review literature. Considering that the majority of weak reviews scored poorly on assessing the methodological quality of the primary studies, transparency, methods for combining or comparing results, conducting a comprehensive search strategy, and data supporting the author's interpretations, review authors should be cognisant of these criteria when conducting systematic reviews. In improving the quality of systematic reviews, the overall goals should ensure there are high quality reviews in all public health topic areas Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: There are promising indicators of demand for reviews, including actions being taken to promote the use of reviews , an awareness of sites providing access to review-level evidence and an increasing number of groups generating summaries of reviews . Despite this heightened activity, given the gaps, a greater investment is needed to provide an evidence base that can meet demand and determine how to apply existing good quality systematic reviews in different contexts . Organizations involved in the conduct of systematic reviews should direct synthesis funding to areas lacking in review content, or should consider higher-level reviews of reviews , Title: Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude", "Passage: Response: We agree that our initial submission did not highlight all the significant innovations and novelty of this work. Based on the Reviewer's suggestions, we have therefore modified the manuscript to highlight those aspects, as listed below. Additionally, we have performed new experiments that further support these innovations. In brief, we have highlighted the following 5 novel aspects of this work:", "Title: Estimating the number of infections and the impact of non-\nPassage: Averaged across all countries, we estimate initial reproduction numbers of around 3.87 , Title: Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture", "Passage: suspicion of an epidemic occurrence in the future) and positive predictive value , which were 0.60-0.70, 0.95-0.98 and 0.20-0.30, respectively, over the last five years 3 . Epidemic warnings are issued when Weekly CPS in a PHC jurisdiction exceeds 30.0. If an epidemic warning has been issued in the past week, it will not be cancelled until the value is lower than 10.0. The reference value for epidemic warnings was also set according to a 1% probability for the occurrence of a series of epidemic warnings in the past five years 3 . Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: epidemic curve begins to increase monotonically in July, when the estimator converges again to 1.12 between day 82 and day 102. The estimate of R 0 under model A converges to 1.21 in late August , which is slightly higher than the estimate from model B. Estimates under both model A and B are similar to the estimate of the effective reproduction number between 1.1 and 1.2 that was proposed in summer of 2009 by . The number of cases required for model B to converge to estimate R 0 of 1.2 and 1.12 up to Day 30 and 82 Title: Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture", "Passage: The lower limit of the 95% credible interval of R t was higher than 1.0 at all jurisdictions without Takachiho in the week of secondary epidemics when Weekly CPS was initially over 10.0. The ratio of the expected value of daily cases of infections from other jurisdictions to that of infections within each jurisdiction was evaluated to estimate the contribution of internal and external infections . Consequently, in Miyakonojo, Kobayashi, and Hyuga, the ratio was higher than 1.0 in the early www.nature.com/scientificreports www.nature.com/scientificreports/ stage of the secondary epidemic. In Miyakonojo, Weekly CPS was higher than 1.0 at the 14 th", "Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan\nPassage: PEDV is believed to infect pigs by both direct and indirect fecal-oral routes. Due to the scales and complexities of modern swine production systems, PEDV is likely transmitted between farms via diarrheic feces or vomitus; contaminated environmental sources involving clinically or sub-clinically infected pigs; trailers used to transport livestock, manure, or food sources; farmers or visitors wearing contaminated clothes; or wild animals and birds . Other potential sources include contaminated fomites , food ingredients or additives, and environmental features such as wind direction, farm altitude, terrain slope, and tree coverage . After an initial outbreak, PEDV may spread at an Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan", "Passage: Although researchers believe that PEDV infections primarily result via fecal-oral routes, the rapid regional spread of the disease raises the possibility of airborne transmission . Support for this hypothesis includes an identified correlation between disease-spread direction and prevailing wind direction , with environmental features such as land coverage, altitude, and slope possibly influencing airborne disease dissemination . To determine specific temporal and geographic relationships associated with PEDV strain transmission, we used phylogenetic, phylodynamic and phylogeographic methods to systematically evaluate potential temporal and spatial transmission routes among Taiwanese swine farms during the 2014 outbreak. Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan", "Passage: increasingly rapid rate due to inadequate farm hygiene management procedures such as improper disinfection and poor biosecurity. The virus can remain dormant in weaning pigs or growth finishing units, eventually triggering mild symptoms and resulting in low mortality rates . Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan", "Passage: a large number of pig farms with high animal densities. Our results are in agreement with findings from previous studies suggesting that excessive farm capacity is a risk factor for the spread of PEDV . Further, aerosol transmission is considered a viable dissemination route in environments marked by high pig densities and close animal proximities . Regarding the negative correlation between PEDV cases and number of feed mills, our data indicate that pig farms at the end of feed routes likely have higher probabilities of infections. Some reports suggest that vehicles used for the dual purposes of transporting swine to", "Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: the United States, please see the World Health Organization news release via https://www.who.int/csr/don/en/ from 14 to 21 January 2020. Using the number of cases exported from Wuhan to other countries, a research group at Imperial College London estimated that there had been 4000 cases in Wuhan with symptoms onset by 18 January 2020, and the basic reproduction number was estimated at 2.6 . Leung et al. drew a similar conclusion and estimated the number of cases exported from Wuhan to other major cities in China , and the potentials of travel related risks of disease spreading was also indicated by Title: Estimating the number of infections and the impact of non-", "Passage: disease-analysis/news--wuhan-coronavirus/. Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: Under-reporting was likely to have occurred and resulted in 469 unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold compared with the situation from 1 to 17 January 2020 on average, and it should be considered in future investigation. We estimated the R 0 at 2019-nCoV to be 2.56 . Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "Passage: Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London on their own homepage on 22 January 2020 that estimated the incidence based on three importation events at 4000 cases . Possible reasons for the slight difference include the number of travelers in the previous study was derived from airline passenger data and the assumed length of T was different. Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases as of 17 January 2020 and a University of Hong Kong group estimated 1343", "Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: treatment . Title: Efficacy of a nonsurgical treatment regimen in patients with bisphosphonate-related osteonecrosis of the jaws in Saudi Arabia\nPassage: The linear model did not identify any significant relationship between the initial area of exposed bone and patient age or duration of bisphosphonate therapy. Only the results from the general linear model showed a statistically significant time-related decrease in the size of exposed bone areas during the nonsurgical therapy from 12.5 \u00b1 12.0 mm to 8.8 \u00b1 10.3 mm , and mean from 25 to 4.25 mm. Complete resolution of the disease was observed in some patients after 2 years . Title: Statin Treatment and Mortality: Propensity Score-Matched Analyses of 2007\u20132008 and 2009\u20132010 Laboratory-Confirmed Influenza Hospitalizations", "Passage: There were 670 pairs in the 2007-2008 sample. For 21 pairs, the treated case subject died within 30 days, but the untreated case subject did not. There were 51 pairs in which the untreated case subject died within 30 days but the treated subject did not. For 1 pair, both the treated and untreated case subjects died, and for 597 pairs, neither case subject died. The results of McNemar's test indicate that the 30-day mortality rates between the treated and untreated groups were significantly different . Title: Lost in Translation (LiT)", "Passage: trigger for discovery after discovery of new and better tolerated, BP lowering agents for the next 20 years. From that followed progressive extension of treatment to less severe elevations of BP. This culminated in the Medical Research Council trial in mild hypertension that began in 1973 and was published in 1985 and had nearly 80 000 patient-years of treatment. The principal result was a marked reduction of stroke, 60 in the treated group and 109 in the placebo group . Today, hypertension is usually managed successfully by family doctors and the most severe forms have virtually disappeared in developed countries.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Although DCs appear to suffer the equivalent of a 'common cold' from MERS-CoV infection, in humans, the virus can be a more serious and opportunistic pathogen associated with the death of up to 40 % of reported cases. It has yet to be established whether infections thought to have been acquired from an animal source produce a more severe outcome than those spread between humans . Studies have established that the mean incubation period for MERS is five to six days, ranging from two to 16 days, with 13 to 14 days between when illness begins in one person and Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In humans, overt disease was given the name Middle East respiratory syndrome, with the acronym MERS. From intermittent animal-to-human spill-over events, the MERS-CoV spreads sporadically among people, causing more severe disease among older adults, especially males, with pre-existing diseases. The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals", "Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?\nPassage: Epithelial cells are the first responders to infections in the lung, followed by the tissue resident alveolar macrophages. They promote viral clearance via phagocytosis, efferocytosis, and release of cytokines and chemokines to promote immune responses . Respiratory viruses like IAV are able to induce suppression and killing of the resident alveolar macrophages . These cells are usually replaced by differentiation of recruited blood derived monocytes into macrophages of different polarization patterns. This in turn creates a delay in pathogen clearance and opens a window for host susceptibility to secondary bacterial infections, colloquially named superinfections . In addition, induction of interferons Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: Epithelial cells are the first responders to infections in the lung, followed by the tissue resident alveolar macrophages. They promote viral clearance via phagocytosis, efferocytosis, and release of cytokines and chemokines to promote immune responses . Respiratory viruses like IAV are able to induce suppression and killing of the resident alveolar macrophages . These cells are usually replaced by differentiation of recruited blood derived monocytes into macrophages of different polarization patterns. This in turn creates a delay in pathogen clearance and opens a window for host susceptibility to secondary bacterial infections, colloquially named superinfections . In addition, induction of interferons Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Respiratory viruses primarily infect and replicate within airway epithelial cells . During the replication process, the cells release antiviral factors and cytokines that alter local airway inflammation and airway niche . In a healthy airway, the inflammation normally leads to type 1 inflammatory responses consisting of activation of an antiviral state and infiltration of antiviral effector cells. This eventually results in the resolution of the inflammatory response and clearance of the viral infection . However, in a chronically inflamed airway, the responses against the virus may be impaired or aberrant, causing sustained inflammation and erroneous infiltration, resulting in the exacerbation Title: Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors", "Passage: To our knowledge this is the first report, which investigates the crosstalk between human PDCs and PBECs. These data highlight possible mechanisms to enhance the production of type-I IFN in the airways, which is critical for host defense against respiratory infections.", "Title: Estimating the number of infections and the impact of non-\nPassage: severely ill patients or for high-risk groups . Looking at case data, therefore, Title: Estimating the number of infections and the impact of non-\nPassage: infection, onset of symptoms and outcome. Title: Cytomegalovirus infection in critically ill patients: a systematic review\nPassage: Attempts to utilize the severity of 'critical illness' to predict CMV infection have not shown a correlation between scoring systems such as APACHE II or SAPS II and the risk of CMV . Severity of illness scores have typically Title: Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections", "Passage: While it has been established that higher viral loads are associated with severe disease, there is discordance in the dengue literature on whether the cellular immune response is protective or facilitates the onset of severe disease . With the risk of developing severe disease depending on circulating cytokine levels, we develop two disease severity parametrizations that differ in the contribution of T-cell-secreted cytokines to disease severity. To discriminate between these different formulations, we then examine the relationship between known virological indicators of disease severity that have been isolated in the clinical literature and the risk of developing severe disease.", "Title: Single\u2010cell transcriptomics reveals distinct inflammation\u2010induced microglia signatures\nPassage: 1. The authors do not mention how many repetitions of their experiment they have done. It should be ensured and clearly stated that n=3 biological replicates were included. Title: Single\u2010cell transcriptomics reveals distinct inflammation\u2010induced microglia signatures\nPassage: 1. The authors do not mention how many repetitions of their experiment they have done. It should be ensured and clearly stated that n=3 biological replicates were included. Title: The Trojan Chicken Study, Minnesota", "Passage: The study design was further limited in that we did not account for time after exposure when photographs were taken. Since participants could drop by any time of the day, the time after exposure and duration of exposure likely varied between participants. In both the feasibility and pilot studies, the return rate was low, and tracking down participants was difficult. If similar studies are conducted in the future, a reward system might be used to increase compliance. Title: Recombination Every Day: Abundant Recombination in a Virus during a Single Multi-Cellular Host Infection", "Passage: Our aim was to analyze viral recombination in a live host. Consequently, we had to deal with the fact that more than one viral replication cycle occurred during the 21 d that infection lasted in our experiment . Based on the kinetics of gene expression , we postulate that each replication cycle lasts between 2 and 3 d, and that therefore seven to ten cycles occurred between infection and the sampling time. In case this assumption is incorrect, we did calculations assuming five, seven, ten, or 20 replication cycles during these 21 d. As shown, the results were not affected", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically: Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study", "Passage: Confirmatory factor analysis, CFA, with AMOS 16 was employed to test the hypothesized measurement model with respect to intention, attitudes, subjective norms and moral norms, specifying the relationship between the observed variables and the underlying latent variables . Thus CFA was used to test whether the Tanzanian and Sudanese data were consistent with an a priori hypothesized 4-factor model. The parameters of the model were estimated with maximum likelihood estimation. Missing data were assumed to be missing at random and was handled using the direct approach in AMOS 16 .", "Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: Influenza is an infectious disease affecting mainly upper respiratory tract worldwide. Influenza virus causes between three and five million severe cases and an estimated 250,000-350,000 deaths annually. In the European Union, there are between 40,000 and 220,000 annual deaths attributable to influenza. However, mortality is only the tip of the iceberg in terms of the disease burden, since influenza also causes a decrease in functional status and increased dependency in the elderly . Estimating the burden of disease caused by influenza is difficult because many cases do not require medical care, or no confirmatory laboratory tests are widely performed to Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: According to World Health Organization statistics, influenza occurs globally with an estimated annual attack rate of 5%-10% in adults and 20%-30% in children . These annual epidemics are estimated to result in approximately 3 to 5 million cases of severe illness worldwide and around 250 000 to 500 000 deaths, which is a major cause of losses in human lives and a grave global public health issue. Title: Comparison of Influenza Epidemiological and Virological Characteristics between Outpatients and Inpatients in Zhejiang Province, China, March 2011\u2013June 2015", "Passage: Influenza virus is estimated to cause 3 to 5 million cases of severe illness and 250,000 to 500,000 deaths each year, while 5%-10% of adults and 20%-30% of children are infected with the influenza virus worldwide . In lower and middle-income countries, influenza could result in large economic burden encompassing direct costs to the health service and households, and indirect costs of productivity losses . Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States and worldwide . In temperate climate countries, including the U.S., influenza activity peaks during the winter months whereas in tropical regions influenza activity may be more variable . Most persons with symptomatic influenza virus infection have self-limited uncomplicated upper respiratory tract illness. One study estimated that during 2010-2016, approximately 8.3% of the U.S. population experienced symptomatic influenza each year . However, complications may result in severe illness, including fatal outcomes. During 2010-2018, an estimated 4.3-23 million medical visits, 140,000-960,000 hospitalizations, and 12, 000-79,000", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: AAV vector systems have a number of engaging properties. The wild type viruses are non-pathogenic and replication incompetent in humans and the recombinant AAV vector systems are even further attenuated . As members of the parvovirus family, AAVs are small non-enveloped viruses that are stable and amenable to long-term storage without a cold chain. While there is limited preexisting immunity, availability of non-human strains as vaccine candidates eliminates these concerns. Modifications to the vector have increased immunogenicity, as well . Title: Viral vector-based influenza vaccines", "Passage: Adeno-associated virus is a parvovirus that is replication-deficient in humans. Like adenovirus, AAV has a broad cell, tissue and host tropism and therefore is a potential good vector vaccine. 218 However, drawbacks of using AAV include: limited capacity for transgenes, presence of pre-existing immunity in humans and the technical challenge of producing high titer stocks. Initially, AAV was not explored as a vaccine vector as it was considered to be poorly immunogenic, however vaccination studies in mice showed that AAV-2 expressing an HSV-2 glycoprotein was immunogenic and a potent inducer of Tcell and antibody responses, 219 and currently modifications are Title: Viral vector-based influenza vaccines", "Passage: being made to AAV to increase immunogenicity. 220 A limited number of studies evaluating AAV as a vector for influenza vaccination has been performed . Initially, an AAV expressing the HA gene or NP gene was shown to be protective in mice. 221, 222 A more recent study tested AAV vaccines expressing the HA, NP or M1 genes of H1N1pdm09 in mice. Whereas AAV-HA afforded full protection from H1N1pdm09 infection, AAV-NP protected mice partially and AAV-M1 did not afford protection. Simultaneous vaccination with all 3 constructs afforded protection from homologous challenge infection. 223 Recently, in an alternative vaccination approach, AAV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adeno-associated viruses were first explored as gene therapy vectors. Like rAd vectors, rAAV have broad tropism infecting a variety of hosts, tissues, and proliferating and non-proliferating cell types . AAVs had been generally not considered as vaccine vectors because they were widely considered to be poorly immunogenic. A seminal study using AAV-2 to express a HSV-2 glycoprotein showed this virus vaccine vector effectively induced potent CD8 + T cell and serum antibody responses, thereby opening the door to other rAAV vaccine-associated studies .", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: inflammatory nature of these diseases . One of the reasons for the involvement of respiratory viruses' in exacerbations is their ease of transmission and infection . In addition, the high diversity of the respiratory viruses may also contribute to exacerbations of different nature and severity . Hence, it is important to identify the exact mechanisms underpinning viral exacerbations in susceptible subjects in order to properly manage exacerbations via supplementary treatments that may alleviate the exacerbation symptoms or prevent severe exacerbations. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s ; with bacterial infections previously considered as the likely culprit for acute exacerbation . However, with the advent of PCR technology, more viruses were recovered during acute exacerbations events and reports implicating their role emerged in the late 1980s . Rhinovirus and respiratory syncytial virus are the predominant viruses linked to the development and exacerbation of chronic airway inflammatory diseases . Other viruses such as parainfluenza virus , influenza virus and adenovirus have also been implicated in acute Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway .", "Title: A Computer-Aided Detection System for Digital Chest Radiographs\nPassage: importance in CAD systems, much research work has been devoted to the segmentation of anatomical regions of the body. Related to thoracic medical imaging, attention is directed particularly to the lungs , the lung fields, the heart and the clavicles , certain lung structures as hilar region , and the liver and neighboring abdominal organs ; the latter two methods do not use simple radiographs, but other 3D image modalities such as CT and MRI. Some authors are also investigating how to segment the bony structures of the chest , often to eliminate the shadows projected on the lung parenchyma. Title: A Computer-Aided Detection System for Digital Chest Radiographs", "Passage: CT images comprising three classes: normal tissue, centrilobular emphysema, and paraseptal emphysema . The present paper is an extension of the preliminary work described in , with a substantial improvement in the proposed method and the experimental validation. Title: Malignant mesothelioma\nPassage: Intravenous contrast-enhanced CT is the primary imaging modality for suspected pleural malignant disease. CT allows visualisation of the whole pleural surface and diaphragm and use of a 45-60 second scan delay enables the pleural surfaces to be studied whilst still allowing assessment of the mediastinal nodes . A standard protocol should include the liver and adrenal glands, but in cases where there is a past history of abdominal or pelvic malignancy, the scan should also include the lower abdomen and pelvis . Title: Chest radiographic data acquisition and quality assurance in multicenter studies", "Passage: lung volume, the presence of nodular densities, parenchymal reticular densities, parenchymal consolidation, cystic lesions, pleural effusions, pneumothorax, hilar adenopathy, heart size, osseous changes, additional abnormalities. A separate score for bronchovascular mark-ings was added to the form after initial assessment of results .", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: Currently, there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin. Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV was recently reported, which shared \u223c96% homology with the SARS-CoV-2 . However, as we know, the human SARS-CoV and intermediate host palm civet SARSlike CoV shared 99.8% homology, with a total of 202 single-nucleotide variations identified across the genome . Given that there are greater than 1,100 nt differences between the human SARS-CoV-2 and the bat RaTG13-CoV , which are distributed throughout the genome in a Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: naturally occurring pattern following the evolutionary characteristics typical of CoVs, it is highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species are the most revealing signs that SARS-CoV-2 evolved by natural evolution. A search for an intermediate animal host between bats and humans is needed to identify animal CoVs more closely related to human SARS-CoV-2. There is speculation that pangolins might carry CoVs closely related to SARS-CoV-2, but the data to substantiate this is not yet published . Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: subunit of 2019-nCoV shares around 70% identity to that of the two bat SARS-like CoVs and human SARS-CoV ), the core domain of RBD are highly conserved ). Most of the amino acid differences of RBD are located in the external subdomain, which is responsible for the direct interaction with the host receptor. Further investigation of this soluble variable external subdomain region will reveal its receptor usage, interspecies transmission and pathogenesis. Unlike 2019-nCoV and human SARS-CoV, most known bat SARSr-CoVs have two stretches of deletions in the spike receptor binding domain when compared with that of human SARS-CoV. But some Title: Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells", "Passage: We observed clear differences in the baseline expression of some genes between the HuH7 and R06E-J cell lines. However, we avoided the complications this issue may cause when comparing homologous human and bat genes by focused on the calculated log 2 -fold changes instead of directly comparing read counts.", "Title: Safe patient transport for COVID-19\nPassage: Mitigating the spread of COVID-19 is a national priority in Singapore , and part of this effort involves planning and conducting safe patient transport for suspected or confirmed cases. HCWs who handle the transport of COVID-19 patients must consider the following principles : firstly, early recognition of the deteriorating patient; secondly, HCW safety; thirdly, bystander safety; fourthly, contingency plans for medical emergencies during transport; fifthly, post-transport decontamination. Specific action steps require designated zones for transport , sufficient supplies of PPE, staff training and support personnel like security officers and cleaning crews. Powered air-purifying respirators add a layer of safety on Title: Safe patient transport for COVID-19", "Passage: Given the continued global spread of COVID-19, we expect that more hospitals will need to deal with this disease. Haphazard transport of infected cases leading to nosocomial spread can stymie efforts to break the chains of transmission. We hope that our suggestions can aid others in ensuring safe patient transport for COVID-19 and reduce nosocomial spread. Title: Safe patient transport for COVID-19", "Passage: Dear Editor, Although COVID-19 has not been officially labelled as a pandemic yet, the global burden of disease is significant and continues to rise. The virus has a high humanto-human transmissibility via airborne, droplet and contact routes . Patient numbers can surge, and hospitals should be ready not just with the infrastructure, but also staff to be familiar with workflows. Kain and Fowler have eloquently detailed influenza pandemic preparations for hospitals and intensive care units, and we feel the principles described in the article are relevant to COVID-19. Staff must consider patient transfers in between wards, as COVID-19 patients are Title: Safe patient transport for COVID-19\nPassage: admitted in isolation facilities to contain infected cases and to avoid nosocomial spread .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: or worse, and secondary bacterial infections have been reported . Disease can progress to acute respiratory distress syndrome and multiorgan system failure . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported . General supportive care is key to managing severe cases . Children under Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: During the study period, i.e., the year 2017, only 119 confirmed cases were reported, which means that the number of MERS-CoV infection cases has decreased in Riyadh and Al-Qassim regions in comparison to that of the last three years. From 2015 to 2016, there was a 25.4% decrease, whereas from 2016 to 2017, it decreased by 48.7%, which translates into a 50% decrease between the two periods. is also complements the findings reported by of Da'ar and Ahmed in their paper . e predominance of infection in males was also observed in another study pwefromed in KSA , which reported Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers .", "Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide\nPassage: The three-dimensional structure of NTCP protein has not been well characterized and the number of transmembrane domains is controversial at present. Several groups have predicted that NTCP has 7-9 transmembrane domains and that the C-terminus of NTCP is located in the cytoplasm . We found that our 9A8 mAb recognizes amino acids 317-326 of NTCP on intact cells without membrane permeabilization, implying that this epitope is possibly exposed to the extracellular space. More precise structural biological studies should be carried out to elucidate the topology of the NTCP protein. Title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", "Passage: Stieger, 2011) . NTCP is a multiple transmembrane glycoprotein presumed to span the cellular membrane up to 10 times with small extracellular loops . It is mainly expressed in the liver , consistent with the liver tropism of HBV and HDV. NTCP localizes to the sinusoidal plasma membrane of hepatocytes , a location that fits well with its receptor role for blood-borne HBV and HDV. Whereas HBV first attaches to hepatocytes mainly through heparan sulfate , our data demonstrate that the interaction between NTCP and L protein of HBV is highly specific, and NTCP is crucial for productive viral entry Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide", "Passage: Immunofluorescence microscopy experiments using our 9A8 antibody revealed that NTCP localized on the plasma membrane, frequently at cell-cell contact sites. This localization was more obvious in a hepatocyte organoid culture system, suggesting that the localization of NTCP may depend on cell polarity. Because the threedimensional culture system recapitulates cell polarity, it is useful for analyzing the function of NTCP in sodium taurocholate transport as well as HBV infection. Recent studies demonstrated that the three-dimensional culture system is suitable for analyzing polarized HBV transmission . It is not well established whether NTCP plays a role in viral transmission in polarized cells, Title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", "Passage: We next cloned human and Tupaia NTCPs and validated the binding of the exogenously expressed NTCPs with the WT b peptide and an N-terminal myristoylated pre-S1 peptide with native residues. Both human NTCP and tsNTCP could be efficiently cross-linked by WT b but not N9K b when expressed in 293T cells as shown by Western blotting with the anti-WT b antibody 2D3 as well as an anti-C9 antibody recognizing the C-terminal C9 tag of the recombinant hNTCP and tsNTCP proteins . WT b but not the control N9K b peptide bound to 293T cells expressing a green fluorescent protein -tagged", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies.", "Title: Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study\nPassage: We used simulated daily total population-level incidence data in the seasonally forced sink population to obtain reproductive numbers that are comparable to empirical estimates of R eff of H3N2 epidemics in the Northern Hemisphere. Growth rates cannot be well estimated when incidence is low in summer seasons, and were therefore calculated only when incidence increased above a tolerance of 10% of the following peak as illustrated in Fig- ure S3. Remaining noise was smoothed with a sliding window of two weeks as in , and the largest growth rate in each season was used to estimate seasonal effective reproductive numbers Title: Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns", "Passage: cases, there may be little or no data to inform a transmission matrix. In this case, a wide variety of matrices can be used to determine the plausible range of values that the estimates can assume. Ultimately deriving a method for estimating these matrices, ideally using Bayesian tools, would mitigate this challenge. The framework we provide here lends itself to such an approach, although we have not carried out such an analysis. Title: Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns\nPassage: al allowing for real-time estimation of R t could be implemented straightforwardly with this modification, as well. Title: Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting", "Passage: Our approach naturally lends itself to Bayesian formulations. As it currently stands our formulation uses a proportional likelihood optimised by exploiting submodularity. However equivalent frameworks exist 3 with explicit likelihoods derived from a survival view point of a temporal point process. These methods can be used within a full Bayesian hierarchical model. This is work that we are currently developing hope to release soon.", "Title: Estimating the number of infections and the impact of non-\nPassage: unable to conclude whether interventions may be different between countries or over time. Title: Estimating the number of infections and the impact of non-\nPassage: varying reproduction numbers in countries where there has been time to observe intervention effects Title: Can informal social distancing interventions minimize demand for antiviral treatment during a severe pandemic?\nPassage: We examined a range of basic reproductive numbers 45] . All natural history parameters and ranges examined in the model are outlined in Table 1 and the parameters have been examined in all possible combinations. Title: Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic", "Passage: There are two reasons for considering household structure in analysing the pandemic influenza situation. First, influenza transmission is known to be concentrated within the household, and thus parameter estimates which ignore this heterogeneity are likely to be frail. Second, many public health policies for future pandemics are likely to be organised around the household. The net effect of social distance measures such as school and workplace closures and cancellation of social gatherings is effectively to reduce transmission out of households . Furthermore, antiviral treatment and prophylaxis and quarantine measures are likely to be targeted at whole households rather than individuals", "Title: Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015\nPassage: Cytogenetic data analysis revealed an incidence of chromosomal abnormalities of 18.35 % among all cases referred to DGMU. Only 10.62 % of these affected subjects have DSCs. Half of these sex chromosome abnormalities were numerical, while the structural disorders and mosaicism were 18.18 % and 31.8 %, respectively. Turner's and Klinefelter's syndromes are the most common DSCs in our patient cohort . Surprisingly, only 25 % of the DSCs were infants indicating a serious delay of diagnosis. Title: Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015", "Passage: are common disorders affecting 1 out of 400 newborns . This high incidence among population is associated to a low abortion rate and encompass a range of chromosomal abnormalities mainly Klinefelter's syndrome, Turner's syndrome, XYY or Jacob's syndrome and Triple X or Superwoman syndrome with an incidence range at birth from 1/500 to 1/2000 . These DSCs have direct impact on biological sex determination, embryonic development and require some medical, social and educational care . In Saudi Arabia, a systematic screening for DSCs is not implemented yet and only referred cases receive this diagnostic service. The objective is to assess Title: Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype", "Passage: an *20% increased risk of acute lymphoblastic leukaemia , and transient myeloproliferative disorder occurring in *10% of DS newborns, of which 10-20% develop acute megakaryoblastic leukaemia before the age of 4 . A detailed knowledge of the genes on the affected chromosome is required to understand the phenotypic effects of aneuploidy. In addition, it is important to determine the overall effects of gene dosage imbalance, which may also be complex. Individuals with partial trisomy 21 resulting from unbalanced chromosomal translocations will only exhibit those features associated with the extra genomic material present. Molecular analysis of these patients enables 'phenotypic mapping' Title: Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015", "Passage: We reported a high incidence of DSCs in Saudi population with a late first diagnosis for these serious abnormalities mainly at adolescence and adulthood suggesting a lack of awareness in the Kingdom that need to be prioritized. This delay might have serious personal, educational, societal and psychological impacts on affected subjects. Therefore, implementation of a routine clinical service for newborn aneuploidy screening and a prevention program included in the premarital testing is highly recommended. In this study we evaluated the effect of co-inhibition of mTOR and receptor tyrosine kinases in AML cell lines.", "Title: Estimating the number of infections and the impact of non-\nPassage: people infected. Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example\nPassage: they had met, and how long they had met with each contact. Out of 770 subjects, 710 subjects recorded how many close contacts they had made. The rest of the 60 subjects provided a range in the number of close contacts they had experienced, and we defined their number of close contacts as the mid-point of this range. The mean number of close contacts for school-aged children and adults was 9.94 and 4.69 respectively. The degree distribution for individuals aged 2-19 is different from those aged 20 and . Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: This review demonstrates that contact surveys typically include of the order of a thousand participants, rely on convenience sampling, and use a retrospective design with paper diaries and self-reporting of contacts over a single day. Major determinants for this number of contactees include characteristics of the respondent , time and their immediate environment . A typical number of different contactees reported per day is in the order of 20 for countrywide studies, a quantity that proved remarkably robust despite the many different study designs. Title: Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1)", "Passage: Subjects were asked to state the number of contacts in the past 24 hours. Contacts were defined by close physical contact as operationalized by a face to face conversation of more than two words in the presence of another individual or physical exposure involving skin contact such as a handshake, hug, or contact during sporting activities. Respondents were provided five ordered categories: less than 5, 5-10, 11-20, 21-50, 51-100, more than 100. Handcock and Jones discuss the phenomenon of heaping and related problems for statistical inference in answering epidemiological questions regarding contact number. Structuring responses within broad ordinal categories avoids", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity. Title: Human resource crises in German hospitals\u2014an explorative study", "Passage: the workload is higher than during regular operations, and at the same time, the number of employees decreases. For example, nearly half of the 2002 SARS epidemic cases in Toronto and Singapore were detected in health-care workers . A pandemic, however, is only one reason for the occurrence of increased numbers of patients and affected hospital staff at the same time. Mass casualty events or natural disasters like a hurricane or an earthquake can cause a similar crisis . Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: The risk for pandemic 2009 virus infection increased with the number of children <18 years of age living in the participant's household, which has previously been reported as a risk factor . In Victoria, the median age of persons with reported pandemic 2009 virus infection was 15 years, with 67% of all notifi ed casepatients being 5-17 years of age . Miller et al. also found that children were predominantly infected . This fi nding, coupled with the diffi culties of maintaining good respiratory etiquette in young children, is a plausible explanation for the effect of child number on infection Title: What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data", "Passage: where RC i is the relative contribution of the i-th factor to the difference. 12 figure 2) . Nevertheless, the number of elderly inpatients only increased by 28.4% during the entire period, whereas admissions for middle-aged patients increased by 30.8% and 54.2%, respectively. Over the 11 years, a 66.4% increase was recorded for women aged 55-64 who were admitted to hospitals, while an increase of 35.4% was recorded for men aged 65 or over.", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 and 766 cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: identified for the period from 2 to 4 February among passengers both with and without close contact . The incidence of infection abruptly dropped after 5 February, the date of movement restriction. Among passengers without close contact, the incidence was estimated to be zero, except for 8-10 February 2020, during which 0.98 persons : 0, 7.74) per day were estimated to have been infected. The epidemic peak among crew members was seen for the period from 8 to 10 February 2020. Figure 3 compares the cumulative incidence with and without movement restriction policy from 5 February. In the presence of Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: of movement restriction that was in place from 5 February onwards. Figure 1 shows the epidemic curve by contact history and type of membership. The highest incidence of illness onset was observed on 7 February. The epidemic curve in a latter half period was dominated by crew members whose movement was not strictly controlled due to the need to continue service on the ship. The second dominating group was passengers with close contact history. The last illness onset date on board of a passenger without close contact was on 14 February. Estimating the incidence of infection, the peak incidence was", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Another recent area of interest is the relationship between asthma and COPD exacerbations and their association with the airway microbiome. The development of chronic airway inflammatory diseases is usually linked to specific bacterial species in the microbiome which may thrive in the inflamed airway environment . In the event of a viral infection such as RV infection, the effect induced by the virus may destabilize the equilibrium of the microbiome present . In addition, viral infection may disrupt biofilm colonies in the upper airway microbiome to be release into the lower airway and worsening the inflammation . Moreover, a viral Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Another mechanism that viral infections may use to drive acute exacerbations is the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. Infection with a multitude of respiratory viruses causes disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells. For example, IFV infection was found to induce oncostatin M which causes tight junction opening . Similarly, RV and RSV infections usually cause tight junction opening which may also increase the infiltration rate of eosinophils and thus worsening", "Title: Vaccination against Paediatric Respiratory Pathogens\nPassage: Acute respiratory infections remain one of the most common major public health threats, accounting for millions of episodes of severe acute lower respiratory infections that result in hospital admissions of otherwise healthy infants and young children worldwide . One-third of the annual deaths occurring in the world are thought to be due to infectious diseases, and respiratory tract infections are responsible for 4 million deaths worldwide each year . According to estimates made by the World Health Organization , pneumonia kills more children worldwide than any other disease, even more than acquired immune deficiency syndrome , malaria and measles combined Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus", "Passage: Text: Viral Respiratory tract infections represent a major public health problem because of their world-wide occurrence, ease of transmission and considerable morbidity and mortality effecting people of all ages. Children are on average infected two to three times more frequently than adults, with acute RTIs being the most common infection in childhood . Illnesses caused by respiratory viruses include, among others, common colds, pharyngitis, croup, bronchiolitis, viral pneumonia and otitis media. Rapid diagnosis is important not only for timely therapeutic intervention but also for the identification of a beginning influenza epidemic and the avoidance of unnecessary antibiotic treatment . Title: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study", "Passage: Frequent and severe respiratory tract infections constitute an important morbidity factor in our society and a considerable cost burden in terms of medical treatment and time of work-loss . RTIs are divided into upper RTIs including common cold, pharyngitis, otitis, sinusitis, laryngotracheitis, epiglottitis and lower RTIs including bronchitis, pneumonia and bronchiolitis . Individual exposure to infectious agents and host factors such as smoking and vitamin D status are believed to contribute to observed differences in RTI risk. In addition, the role of overweight = 25.0-29.9 kg/m 2 ) and in particular obesity in predisposition to RTIs is increasingly discussed . Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Text: Acute Respiratory Infections and lower respiratory tract infections ) are a major cause of death among children under 5 years old particularly in developing countries where the burden of disease is 2-5 times higher than in developed countries . While these viruses usually cause mild cold-like symptoms and can be self-limiting, in recent years novel coronaviruses such as severe acute respiratory syndrome and Middle East respiratory syndrome have evolved and infected humans, causing severe illness, epidemics and pandemics . Currently, the majority of all infectious disease outbreaks as recorded by the World Health Organization occur in the continent of", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Orf8 orf8 is an accessory protein found in the Betacoronavirus lineage B coronaviruses. Human SARS-CoVs isolated from early-phase patients, all civet SARS-CoVs, and other bat SARS-related CoVs contain fulllength orf8 . However, a 29-nucleotide deletion, Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Bat which causes the split of full length of orf8 into putative orf8a and orf8b, has been found in all SARS-CoV isolated from mid-and late-phase human patients . In addition, we have previously identified two bat SARS-related-CoV and proposed that the original SARS-CoV full-length orf8 is acquired from these two bat SARS-related-CoV . Since the SARS-CoV is the closest human pathogenic virus to the 2019-nCoV, we performed phylogenetic analysis and multiple alignments to investigate the orf8 amino acid sequences. The orf8 protein sequences used in the analysis derived from early phase SARS-CoV that includes full-length orf8 , the mid-and late-phase Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: SARS-CoV that includes the split orf8b , civet SARS-CoV , two bat SARS-related-CoV containing full-length orf8 , 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5 ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: A novel short putative protein with 4 helices and no homology to existing SARS-CoV or SARS-r-CoV protein was found within Orf3b . It is notable that SARS-CoV deletion mutants lacking orf3b replicate to levels similar to those of wildtype virus in several cell types , suggesting that orf3b is dispensable for viral replication in vitro. But orf3b may have a role in viral pathogenicity as Vero E6 but not 293T cells transfected with a construct expressing Orf3b underwent necrosis as early as 6 h after transfection and underwent simultaneous necrosis and apoptosis at later time points . Orf3b was also", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November. Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Middle East respiratory syndrome was first reported in September 2012 in Saudi Arabia, following isolation of MERS-CoV from a male patient who died months earlier from severe pneumonia and multiple organ failure . In the 8 years since then, there have been more than 2494 confirmed cases of MERS resulting in upwards of 858 deaths globally . While 27 countries have reported cases of MERS, approximately 80% of confirmed cases originated in Saudi Arabia . To date, all known cases of MERS can be linked to travel or residence in countries along the Arabian Peninsula-that is, Bahrain; Iraq; Iran; Israel, Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Text: A respiratory viral disease caused by the Middle East Respiratory Syndrome CoronaVirus was first isolated in 2012, in a 60-year-old man who died in Jeddah, KSA due to severe acute pneumonia and multiple organ failure . Since then, 27 countries have reported the presence of this virus, including the 12 countries of the Eastern Mediterranean region. Several outbreaks have occurred in multiple countries including Saudi Arabia, the United Arab Emirates and the Republic of Korea . Recent fatality rate of 21% . Very limited evidence is available for exploring the epidemiology of this virus among the pediatric population .", "Title: Nanoparticle Vaccines Against Infectious Diseases\nPassage: result in better stimulation of the host immune response . Title: Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy\nPassage: The development of new adjuvants has been guided in the last years by the detailed comprehension of the central role played by the innate immunity to initiate and direct the adaptive immune response. In particular, the pattern recognition receptors in cells of the innate immune system act as sensors for bacterial and viral nucleic acids and induce the innate immune response by activation of a signaling cascade resulting in the upregulation of inflammatory cytokines, chemokines, and type I IFNs. This will eventually end up in triggering a robust adaptive immune response . Therefore, PRRs represent the ideal target for vaccine Title: A cascade reaction network mimicking the basic functional steps of acquired immune response", "Passage: When immune tolerance has been surpassed, antigen-specific immune response is triggered to eliminate foreign agents. Many mechanisms act in a coordinated and sequential manner to recruit different cell populations, mainly B and T cells, and promote the production of antibodies, as well as proinflammatory cytokines and chemokines. For example, after antigens have been transported to lymph nodes, they are digested into smaller fragments for presentation by Antigen Presenting Cells , allowing for T cell recognition and the initiation of cytotoxic processes, such as the production of cytokines and antibodies. Title: A cascade reaction network mimicking the basic functional steps of acquired immune response", "Passage: When immune tolerance has been surpassed, antigen-specific immune response is triggered to eliminate foreign agents. Many mechanisms act in a coordinated and sequential manner to recruit different cell populations, mainly B and T cells, and promote the production of antibodies, as well as proinflammatory cytokines and chemokines. For example, after antigens have been transported to lymph nodes, they are digested into smaller fragments for presentation by Antigen Presenting Cells , allowing for T cell recognition and the initiation of cytotoxic processes, such as the production of cytokines and antibodies.", "Title: Clinical review: Mass casualty triage \u2013 pandemic influenza and critical care\nPassage: and case fatality rates during a pandemic, including the potential for more than one wave. The base scenario assumes a clinical attack rate of 25% and a case fatality rate of 0.37%, giving rise to 53,700 excess deaths in the UK. A reasonable worst case scenario involves a cumulative clinical attack rate of 50% with 2.5% case fatality, causing 709,300 excess deaths. Similarly, the US Department of Health and Human Services predicts that in a \"moderate\" scenario based on a virus with 1968-like pathogenicity, 865,000 will require hospitalisation and 65,000 will require ventilation. They also outline a \"severe\" 1918-like scenario Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season", "Passage: In 2009, the rapid spread of an emerging influenza virus, A of swine origin, resulted in the first pandemic of the 21 st century . This pandemic influenza A 2009 virus has led to a limited outbreak in the Netherlands with, as in many other countries, generally mild illnesses in the majority of patients . The pandemic was considerably less lethal than was expected, with a low overall case fatality rate . Nevertheless, a considerable part of the pandemic influenza related deaths concerned relatively young persons . This is contrary to seasonal influenza epidemics, where deaths occur mainly amongst elderly Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season", "Passage: Data on clinical presentation was available for 42 of the 65 fatalities during the pandemic seasons and for 28 of the 38 during the 2010-2011 season . In both seasons, fatal cases presented mainly with respiratory symptoms , including acute respiratory distress syndrome , followed by systemic symptoms . Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season\nPassage: The peak in mortality rates in persons aged between 55 and 64 years observed during the 2009-2010 pandemic, shifted to older age groups in the 2010-2011 influenza season. Furthermore, the peak in mortality rates in children younger than 15 years of age decreased considerably.", "Title: The origins of the great pandemic\nPassage: and answer, finally, why this pandemic was so catastrophic. Title: 1918 Influenza: the Mother of All Pandemics\nPassage: why was it so fatal? No Virus from 1918 had been isolated, Title: Avian influenza outbreak in Turkey through health personnel's views: a qualitative study\nPassage: things. She slept with the doll for many nights. Why didn't anyone underline this occasion? Why was the people's psychological status not taken into account? Why wasn't attention paid to the problems related to the housing infrastructure or the lack of clean water? I still can't accept this; it still affects me.\" Title: Early Days of Food and Environmental Virology\nPassage: tract. It is unfortunate that the apparent reactivation of coproantibody-neutralized virus, which would have occurred upon ingestion, was not given more weight , as this finding may well have had greater public-health significance than the grape-juice results.", "Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1\nPassage: The results of the simulations are given in Figure 1 and 2. Consistent with our theoretical results we observe that when the reporting fraction is constant, the estimates of R0 are unaffected by a failure to control for missingness. However if the reporting fraction increases, then the estimates are smaller when we adjust for the missingness. We also note that has recently described a tendency of this method to overestimate the mean of the serial interval when the serial interval is short, such as in cases of influenza. Thus part of the effect seen could be attributed to this phenomena, Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak", "Passage: Another limitation is that the focus on EVD may not allow readers to extrapolate to other issues of health or medicine. Furthermore, we cannot draw causation from our findings. It is unknown if any reporters, politicians, or pundits made inaccurate statements due directly to the lack of clarity in the academic reviews. However, this work may still achieve its goal of comparing the contemporaneous academic reviews available to reporters and policy makers at the time of their background research. Lastly, this analysis stops with the outbreak's containment, which therefore overlooks the long-term chronic pains and visual changes that have plagued Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak", "Passage: made Western Africa susceptible for an EVD outbreak included densely populated cities, porous borders, and the profound poverty and under resourced health care systems of the region. A few sources postulated that food insecurity due to climate-change is also theorized to have spurred the outbreak as it increased the need for reliance on the consumption of 'bush meat' that could have come from infected animals . These authors also implicated deforestation as a possible contributor to the outbreak by increasing the interaction of humans with the newly displaced animal population, particularly bats, which are presumed to be the animal vectors Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak", "Passage: Well-meaning reporters that looked to academia for clarity would seem more likely to mistakenly concluding that airborne transmissibility was a possibility worthy of prompting policy changes if traditional measures of journal status like impact factor were of poor guidance, 1 in 3 academic papers failed to discuss airborne spread, and 1 in 3 of those that did cover it failed to communicated that no specific actions should stem from this negligible risk. As another example, a debate over the potential for EVD to be contracted from a bowling ball may never be settled in academia. Even with a dedicated study", "Title: Estimating the incidence and diagnosed proportion of HIV infections in Japan: a statistical modeling study\nPassage: undiagnosed individuals, considering that the incubation period in most cases of HIV infection is now considerably extended by ART. The drawback of the latter calculation is that patients with AIDS who have survived and have received ART are excluded; thus, the calculated proportion may not be strictly in line with the target figure in the first goal of the 90-90-90 initiative. Therefore, when estimating the undiagnosed number of HIV infections and the diagnosed proportion at the end of 2017, both calculations are made, and the former is adjusted by subtracting 2,321 AIDS deaths from the cumulative count of AIDS cases. Title: Estimating the incidence and diagnosed proportion of HIV infections in Japan: a statistical modeling study", "Passage: in which it was estimated that 85.6% of HIV-infected individuals, regardless of nationality, were diagnosed . Nevertheless, it is known that the analysis of voluntary blood donation data is prone to sampling bias of donors owing to the tendency of people with high risk to repeatedly undertake anonymous laboratory testing through the practice of blood donation , and moreover, an exclusion of repeaters can result in underestimation of the prevalence, resulting in overestimation of the fraction diagnosed, even though such screening of a large number of people is very costly. Considering the need to achieve continued monitoring of the diagnosed Title: Estimating the incidence and diagnosed proportion of HIV infections in Japan: a statistical modeling study", "Passage: increased with time, and females tended to yield higher estimates than males. In the latest time interval from 2013-2017, the diagnosed proportion was estimated at 75.3% among males and 82.1% among females. Figure 5 shows the undiagnosed number of HIV infections and the proportion of diagnosed infections at the end of 2017. The uncertainty bound was greatest with an assumed median incubation period of 12.3 years, with an estimated 6,552 infections . Figure 5B shows the diagnosed proportion, including and excluding AIDS cases, with 95% confidence intervals. Even when AIDS cases were included, the 2,321 deaths known up to that Title: Estimating the incidence and diagnosed proportion of HIV infections in Japan: a statistical modeling study", "Passage: therapy , and 90% of people receiving ART have suppressed viral loads . UNAIDS even aims to achieve 95-95-95 at a global level by the year 2030, contributing to successfully controlling HIV and AIDS, as supported by the so-called test-and-treat strategy . To quantify the situation of each country, monitoring diagnosed individuals is essential; moreover, estimation of the diagnosed proportion of HIV infections must be supported by firm scientific methods, to estimate the first part of the three 90-90-90 targets, i.e., 90% of HIV-infected people know their HIV status. In Japan, an analysis of blood donors took place in 2017,", "Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort\nPassage: Community acquired pneumonia is common, affecting between 5 and 11 individuals per 1,000 of the adult population each year and is the commonest cause of sepsis, severe sepsis and septic shock . Between 22 and 42% of patients require hospital admission of whom 5 to 10% will be admitted to an ICU . Hospital and ICU admission rates for CAP are increasing for all ages . An ageing, more vulnerable population, earlier recognition of deteriorating patients and better availability and use of intensive care beds may in part explain this increase. Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort", "Passage: A total of 718 patients had one or more co-morbid conditions, with cardiac and respiratory disease affecting 458 and 531 patients, respectively. Chronic obstructive pulmonary disease was documented in 278 patients, diabetes mellitus in 19.6% and a chronic neurological condition in 13.1%. Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort\nPassage: Between 29 September 2005 and 13 October 2009, 1,170 patients were enrolled. Four individuals were excluded because of missing or inconsistent data. Patient characteristics are shown in Table 1 . On admission, 1,135 patients met IDSA/ATS criteria for severe CAP, 991 on major criteria and 146 on minor criteria. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: . Pneumonia deaths decreased from 1.8 million in 2000 to 900,000 in 2013 . These data do not reflect the full impact of increasingly widespread use of pneumococcal conjugate vaccine in low-and middle-income countries because the incidence of pneumonia and number of deaths are likely to decrease still further as a result of this widespread intervention .", "Title: Excess healthcare burden during 1918-1920 influenza pandemic in Taiwan: implications for post-pandemic preparedness\nPassage: Our results indicate that there was a considerable extra burden on the public medic system during the initial wave of the epidemic in 1918, with a significant loss of lives reported by both the public medic system and the 12 large public hospitals. In comparison, only a substantial number of excess hospitalizations in the public hospitals was reported in 1920, indicating that the population was relatively unprepared for the first wave in 1918 and did not fully utilize the public hospital system. Title: Lessons learned from the 1918\u20131919 influenza pandemic", "Passage: private physicians . The curative physicians, primarily general practitioners, were overwhelmed by the cases of infl uenza and relied on traditional methods to cope with the illness ranging from aspirin, quinine, opium, ammonia, alcohol, camphor, eucalyptus and iodine to musk, wet packs, blood serum, creosote, turpentine, cinnamon and turtle soup . At best, these prescriptions offered symptomatic relief, and some actually harmed the patients. In the United States, the 1918 pandemic was met with local quarantines, and large public gatherings were discouraged, and like Great Britain folk remedies were widely used . There was no coordinated information from medical authorities Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: Additional reports of the first wave of the virus in the spring of 1918 suggest that the pandemic originated with Chinese workers at Camp Funston, Kansas, where the workers began suffering from 2 to 3 day fevers, gastrointestinal symptoms, and general weakness . Within 3 weeks 1100 soldiers had been hospitalized, and thousands more had received out-patient treatment . The illness was able to spread to other military camps within the US, before traversing the Atlantic Ocean via soldiers supporting Allied operations in Europe. The US Army reported that from March-May 1918, 11.8% of US soldiers were hospitalized due to Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: . Further, reports from Philadelphia, Pennsylvania stated that across 31 hospitals in the city, every hospital bed was occupied by patients with influenza . The pandemic was especially problematic in highly isolated communities where many individuals had limited contact with prior influenza strains, thus lacking any pre-existing immunity. For example, some Inuit settlements reported case mortality rates as high as 70%, while certain communities in Africa were completely decimated . Interestingly, individuals who had been infected throughout the first wave seemed to be protected against this secondary wave, and recent analyses have suggested that these individuals had up to 94%", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: In summary, 2019-nCoV is a novel lineage B Betacoronavirus closely related to bat SARS-related coronaviruses. It also has unique genomic features which deserves further investigation to ascertain their roles in viral replication cycle and pathogenesis. More animal sampling to determine its natural animal reservoir and intermediate animal host in the market is important. This will shed light on the evolutionary history of this emerging coronavirus which has jumped into human after the other two zoonotic Betacoroanviruses, SARS-CoV and MERS-CoV.", "Title: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997\u20132006)\nPassage: In a collaborative effort to answer these questions and perhaps to improve the accuracy of influenza strain forecasting and vaccine composition , it is also hoped that this study will encourage more researchers in Southeast Asia to make their influenza sequences publicly available for analysis -especially whole genome sequences where resources permit, and particularly sequences from more tropical countries where influenza is prevalent all year round, with less well-defined seasonal peaks. Title: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997\u20132006)", "Passage: In summary, this study has provided additional data from Hong Kong to support a mainly migratory mechanism to explain the underlying seasonality of influenza A viruses. However, there may be small localities of so-called 'latency' where viruses remain circulating at low levels within that local population, to reemerge during the influenza season of the following year, with relatively little genetic change. This may affect only a minority of these populations, with the majority being infected by newly imported influenza viruses from elsewhere. These concepts are summarized in Figure 1 . Title: Travellers and influenza: risks and prevention", "Passage: Among the challenging epidemiological aspects of seasonal influenza in travellers are differences in seasonality and virus strains between climate zones and between northern and southern hemispheres. In tropical areas, influenza viruses may circulate throughout the year with several seasonal peaks, whereas in the moderate climate zones, circulation is largely limited to one or two peaks in the fall and winter months. 12 Recent data have revealed interesting patterns of emergence and spread of antigenic drift variants, showing the global circulation of the different seasonal influenza viruses. These observations have major implications for selection of viruses that should be represented in Title: Ad Hoc Influenza Vaccination During Years of Significant Antigenic Drift in a Tropical City With 2 Seasonal Peaks: A Cross-Sectional Survey Among Health Care Practitioners", "Passage: influenza seasons are January to March and June to August, 8 and the government has opted to offer the Northern Hemisphere vaccine once a year in October to December. In early 2015, a heavy flu season occurred due to the newly drifted influenza strain, A H3N2 Switzerland that had not been included in the Northern Hemisphere vaccine. In view of the reduced level of protection as reported elsewhere, 9 the Hong Kong Government decided to place an additional procurement of Southern Hemisphere vaccine that contains the new virus strain. Given the limited supply, the additional dose of vaccine was only", "Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919\nPassage: during the 1918 pandemic were in those aged 20-40 years . Influenza and pneumonia fatality rates in those aged 15-34 years were more than 20 times higher than in previous years and absolute risk of influenza-related death was higher in those < 65 years of age than those > 65 years old . It is still not fully understood why this occurred, but it is possible that an antigenically similar influenza strain circulated prior to 1889, providing a level of protection against the novel H1N1 pandemic strain to those born prior to 1889 . Additionally, archaeserological and epidemiological evidence have Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: of the 2009 pandemic virus, allowing researchers to predict that a lack of protection, and thus a high mortality rate may be seen in healthy, young adults throughout the 2009 H1N1 pandemic . Thus, when vaccines were limited during the early stages of the 2009 pandemic, young adults were prioritized over the elderly, who demonstrated some degree of protection to this influenza strain, resulting in a lower mortality rate in young, healthy adults . The average age for laboratory-confirmed fatalities during the 2009 pandemic was 37 years in the US, supporting this vaccine prioritization initiative . Additionally, the awareness of Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: Classically, fatal influenza infections are primarily associated with the very young and the elderly resulting in a characteristic \"U\"-shaped mortality curve . Interestingly, however, the 1918-1919 H1N1 influenza pandemic mortality curve exhibits a \"W\"-shape due to excess mortality in young adults 20-40 years of age due to influenza-related illness. It has been postulated that the increased disease severity in young adults was likely associated with immune status due to the lack of pre-existing immunity in this population . Further, more than 99% of fatal infections occurred in those < 65 years of age and nearly 50% of all influenza-related deaths Title: Global Mortality Impact of the 1957\u20131959 Influenza Pandemic", "Passage: Age-specific excess mortality rates were highest at both extremes of the age spectrum . However, when excess mortality was compared to baseline mortality rates, the age groups with highest relative burden were 15-24 years , followed by 5-14 years . In contrast, children aged <5 years and seniors aged \u226565 years only experienced a minor elevation over baseline . The sharp mortality elevation in schoolaged children and young adults was consistent throughout Europe , even though the all-age impact of the pandemic on mortality was generally low in this region.", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: When biomedical innovations fall into the 'Valley of Death', patients who are therefore not reached all too often fall with them. Being entrusted with the resources and expectation to conceive, deliver and communicate dividends to society is both cherished and eagerly pursued at every stage of our careers. Nevertheless, the road to research translation is winding and is built on a foundation of basic research. Supporting industry-academia collaboration and nurturing talent and skills in the Indo-Pacific region are two of the four pillars of the National Innovation and Science Agenda. 2 These frame Australia's Medical Research and Innovation Priorities, which Title: Exposure science in an age of rapidly changing climate: challenges and opportunities\nPassage: collect high quality bird count data 103 on this scale using existing scientific research funding. Title: Global public goods and the global health agenda: problems, priorities and potential", "Passage: in which we discuss Advance Purchase Commitments and other financial innovations. Title: Between Scylla and Charybdis: reconciling competing data management demands in the life sciences\nPassage: In the first decade of the 21st century a number of highly influential reports were issued in order to delineate these concerns within the life sciences. The first, issued by the US National Research Council , was entitled Biotechnology Research in an Age of Terrorism and focused attention to a list of \"experiments of concern\" -research with considerable potential for weaponization. A second, from the National Science Advisory Board for Biosecurity , Globalization, Biosecurity and the Future of the Life Sciences , advocated the establishment of a \"web of prevention\" model taking into consideration the multifaceted actions needed to address", "Title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans\nPassage: Bats, members of the mammalian order Chiroptera, have evolved a range of characteristics that allow them to adapt to changing environmental conditions. They are the only mammals capable of powered flight, most bat species undergo torpor to conserve energy and species that inhabit high northern latitudes hibernate for up to eight months with body temperatures below 10uC . Bats are extremely diverse, making up a fifth of all known mammalian species. They occupy a variety of niches across most of the world where they contribute in many ways to ecological balance . Title: High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress", "Passage: Bats are the only mammal that have mastered true flight, and consequently, they must endure elevated body temperatures throughout flight. Additionally, most have longer lifespans than terrestrial mammals of similar body sizes, despite their high metabolic rate and its predicted consequences on oxidative metabolism. As such, they have one of the greatest disparities between body mass and longevity . Their longevity has been attributed, at least in part, to enhanced oxidative stress resistance and protein homeostasis Yin et al. 2016) . The body temperature of bats raises drastically during flight , and there is an excessive increase in metabolic rate Title: High basal heat-shock protein expression in bats confers resistance to cellular heat/oxidative stress", "Passage: It is conceivable and generally accepted that major evolutionary adaptation is required for bats to sustain its ability to fly. Recent comparative genomics studies have confirmed that bats are different to all other mammalian groups . However, it is extremely difficult to pinpoint major genetic adaptations to explain why bats have a relatively longer lifespan or to their apparent reservoir host potential. The adaptations required to sustain a high rate of metabolism and high body temperature during daily flight may provide insight. While proving high basal HSP expression of bats is an adaptive evolution from flight is not possible without Title: ABCB1 protects bat cells from DNA damage induced by genotoxic compounds", "Passage: up to 10 times longer than would be expected given their body size. This is what makes bats an interesting species to explore exceptional longevity and therefore has driven this study. Although they refer to Max Rubner's rate of living theory they really don't explore what this means in terms of making bats outliers. They need to highlight why bats are so unique given their longevity. This is not clear throughout.", "Title: Sounding the Alarm: Health in the Anthropocene\nPassage: Human population has increased from about 200 million 2000 years ago to almost 7.5 billion today , a multiple of almost 40. It has doubled since about 1970, when its rate of annual increase peaked at over 2%. Since then the growth rate has fallen, but world population still rises by over 80 million per annum . The increase in human population has also been made possible by transformation of the biosphere to meet human wants and needs. The biosphere refers to the thin film beneath, on and above the surface of the Earth in which interaction occurs between living Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: to changes in the age distribution of the population only, if the size of the population had remained constant, and the age-and sex-specific death rates also remained unchanged. 9. How many people become sick each year? Title: Oral health in China \u2013 trends and challenges\nPassage: the largest aging society in history . The change of population will have major effects on oral health . In the same time, many rural people have rushed into the city, altering the rural to urban population proportion a great deal . The rural population has decreased from 73.6% of the total population in 1990 to 57.0% in 2005. A few years later, this proportion will further decrease to about a half. Meanwhile, the great changes in lifestyle will affect their general and oral health. These demographic changes will alter disease patterns, cultural attitudes, health behaviors and the health care Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: The relative impact of demographic and epidemiological change on the projected numbers of deaths by cause is shown in Figure 17 . The change in the projected numbers of deaths globally from 2004 to 2030 can be divided into three components. The first is population growth, which shows the expected increase in deaths due to the increase in the total size of the global population, assuming there are no changes in age distribution. The second is population ageing, which shows the additional increase in deaths resulting from the projected changes in the age distribution of the population from 2004 to", "Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients\nPassage: Text: The health and economic burdens associated with acute respiratory infections by influenza and respiratory syncytial viruses are significant in Australia and overseas. 1-3 Polymerase chain reaction testing is effective for confirming respiratory viral infections. 4 Multiplex PCR can detect numerous respiratory viruses, including influenza and parainfluenza viruses, RSV, adenovirus, rhinovirus, human metapneumovirus, enterovirus, bocavirus and coronavirus with very high sensitivity and specificity. 5 Although the results of standard multiplex PCR are accurate and comprehensive, it has traditionally been performed in a central laboratory with a lengthy turnaround time, which may be inconvenient in settings where test results are urgently Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: The rapid PCR system in our study accurately detects influenza viruses A/B and RSV but, unlike the standard multiplex PCR, cannot detect other clinically relevant respiratory viruses, such as rhinovirus, coronavirus, human metapneumovirus, parainfluenza virus, adenovirus, enterovirus, and bocavirus. If infection with other respiratory viruses is suspected, patients may therefore need further investigations. Standard multiplex PCR can provide broader information, as it can detect multiple respiratory viruses in a single run, although the long turnaround time restricts its suitability for urgent clinical decision making. Improving the turnaround time of multiplex PCR analysis may achieve better outcomes. Title: Application of Molecular Diagnostic Techniques for Viral Testing", "Passage: With respect to parainfluenza viruses, types 1 to 4 have been associated with bronchiolitis, croup and pneumonia in children, but also in elderly and immunocompromised patients. PCR is an adequate technique for the detection of parainfluenza virus, above all in immunocompromised patients . PCR has a sensitivity of 100% and specificity that range 95-98% if compared with culture method . Multiplex PCR assays can differentiate between a wide variety of respiratory pathogens . Also, a rapid and sensitive multiplex real-time PCR assay for detection of four serotypes of parainfluenza viruses has been developed . Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: For each specimen, assays for ten common and newly identified viruses were performed. Briefly, WUPoyV and BOV were tested using monoplex PCRs described previously. 18, 19 Other viruses were tested using the Luminex platform and multiplex xTAG TM respiratory viral panel assay according to the manufacturer's instructions. 20 All multiple infection samples were retested. If there was discordance between two tests, the sample was confirmed by monoplex PCR.", "Title: Estimating the number of infections and the impact of non-\nPassage: of the novel coronavirus disease 2019 outbreak in China. doi:10.1101/2020.03.19.20039107. Title: Estimating the number of infections and the impact of non-\nPassage: In China, strict movement restrictions and other measures including case isolation and quarantine Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: epidemic curve begins to increase monotonically in July, when the estimator converges again to 1.12 between day 82 and day 102. The estimate of R 0 under model A converges to 1.21 in late August , which is slightly higher than the estimate from model B. Estimates under both model A and B are similar to the estimate of the effective reproduction number between 1.1 and 1.2 that was proposed in summer of 2009 by . The number of cases required for model B to converge to estimate R 0 of 1.2 and 1.12 up to Day 30 and 82 Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: Under-reporting was likely to have occurred and resulted in 469 unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold compared with the situation from 1 to 17 January 2020 on average, and it should be considered in future investigation. We estimated the R 0 at 2019-nCoV to be 2.56 .", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: cold symptoms than placebo treated patients in the intention-to-treat population . The anti-influenza activity was shown by subgroup analysis of 49 influenza infected patients who benefited from a 3.3 days faster recovery from symptoms. The use of carrageenan nasal spray was associated with a significant reduction of the influenza viral load in nasal fluids and a significant increase in the number of virus free patients within the treatment period of 7 days. In good accordance Prieschl-Grassauer are co-founders of Marinomed Biotechnologie GmbH. Marinomed Biotechnologie GmbH had a role in study design, data collection and analysis, decision to publish, preparation of Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: to the broad antiviral effectiveness of carrageenan, patients will receive in parallel a treatment of concomitant viral infections. Therefore, patients will benefit from a decreased probability to develop complications. In consideration of the complications known to accompany an influenza virus illness this combinational therapy meets an urgent medical need. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: We found that the combination of carrageenan with 3 mg/kg BW/day Zanamivir used for treatment of H7N7 infected mice resulted in significantly enhanced survival of mice in comparison to both mono-therapies . The significantly enhanced survival compared to the placebo treated group was also found after a delayed treatment start 48 hpi. Furthermore, in the H1N1pdm model the combination of carrageenan with 1 mg/kg BW/day Zanamivir showed statistically significant enhanced survival in comparison to placebo treatment even after a treatment start 72 hpi. This is a remarkable finding since NIs are normally not effective when applied 72 hpi.", "Title: Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone \u2020\nPassage: To define which molecules were more selective against cancerous cells, the selectivity index , defined as Vero IC 50 over HeLa or Jurkat IC 50 values, was calculated. Title: Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone \u2020\nPassage: . According to the estimate of Vlietinck et al. , a purified natural molecule is considered to have a relevant or moderate antiviral activity when the reduction factor of viral titer is \u22651 \u00d7 10 3 or 1 \u00d7 10 2 , respectively. In this study, we define the Rf of 1 \u00d7 10 1 or \u22651 \u00d7 10 2 for mild or moderately active substances, respectively. Title: The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study", "Passage: Cell lines of A549, MCF-7, DU145 and HepG2 were provided by Nanjing KeyGen Biotech. Inc. All of these cells were cultured in Dulbecco's modified Eagle's medium containing 10% calf serum and grown in a humidified atmosphere of 5% CO 2 at 37\u00b0C. Title: Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone \u2020\nPassage: Currently, it is necessary to discover new and better antivirals with novel mechanisms of action for the treatment of Human Herpesvirus type 1 and 2 infections, mainly for the treatment of immunocompromised and transplanted patients, considering the continuous emergence of HHV acyclovir-resistant strains. Moreover, to discover medicines for Dengue disease is imperative, taking into account the impact of this disease on public health.", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: More than 50% of patients who suffer from severe CHIKF are over 65 y old, and more than 33% of them die. Most adults who suffer from severe CHIKF have underlying medical conditions . The other group that is disproportionately affected by severe CHIKV is children. Other complications associated with CHIKV, from most common to least common, include respiratory failure, cardiovascular decompensation, meningoencephalitis, severe acute hepatitis, severe cutaneous effects, other central nervous system problems, and kidney failure . Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years . Title: CDC Summary 21 MAR 2020,\nPassage: cases in the United States by age group found that 80% of deaths were among adults 65 years and older with the highest percentage of severe outcomes occurring in people 85 years and older. Title: CDC Summary 21 MAR 2020,\nPassage: Older adults, with risk increasing by age.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: the percentage of confirmed cases among males to be 66%, compared with 34% among females .", "Title: Exposure science in an age of rapidly changing climate: challenges and opportunities\nPassage: . As noted above, the 2015 ISES Meeting was an important motivation for this paper and for the case study topics presented. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: This study was approved by the Massey University Human Ethics Committee: Southern A . Written informed consent was obtained from all participants. Title: A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan\nPassage: sample material. Title: Identification of antigens presented by MHC for vaccines against tuberculosis\nPassage: Further information on research design is available in the Nature Research Reporting Summary linked to this article", "Title: 2,500-year Evolution of the Term Epidemic\nPassage: but where does it come from? Title: 2,500-year Evolution of the Term Epidemic\nPassage: Semantic confusion caused the great Emile Littr\u00e9, who translated Hippocrates' works into French in the first half of the 19th century, to make a nosologic error. Hippocrates described what is known today, since the work of Littr\u00e9, as the Cough of Perinthus. This account can be found in Epidemics book VI. Hippocrates described coughs that started toward the winter solstice and were accompanied by many symptoms: sore throat, leg paralysis, peripneumonia, problems with night vision, voice problems, difficulty swallowing, difficulty breathing, and aches. When Littr\u00e9 published his translation and commentaries on Epidemics in 1846, he mistakenly considered the Cough of Title: Lost in Translation (LiT)", "Passage: The translations of animal models of disease to man pose many difficulties. Many human diseases progress slowly over years, and as the condition evolves, different features appear. Environmental effects may be more important than genetics. Tissue inflammation may progress through different cell types and ultimately to fibrosis, for example, cirrhosis and advanced renal disease. Cardiovascular hypertrophy may be infiltrated by fibrosis and even calcification and become irreversible. It is very difficult to replicate either the aetiology or the temporal evolution in a laboratory animal model. From a biologist's standpoint, disease models are the mainstay of their evidence to take a Title: 2,500-year Evolution of the Term Epidemic", "Passage: According to Grmek, \"Littr\u00e9 took chapter VI, 7.1 as a general description of an epidemic in the sense of this word in the medical language of the 19th century rather than in the sense intrinsic to the works of Hippocrates. In the Corpus Hippocraticum, the noun 'epidemic' designates a collection of diseases observed at a given place, during a given period. A disease described as epidemic, such as epidemic cough, is a condition occurring from time to time in a given place, the appearance of which is closely linked to changes in season and climatic variations from year to year\"", "Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: can lead to development of a cough, rhinitis, fever and other common clinical symptoms . In some cases, it can cause respiratory distress, hypoxia, wheezing and other severe respiratory symptoms . Clinical diagnosis is mainly pneumonia, bronchitis, pneumothorax, mediastinal emphysema and otitis media and other complications . In some cases, patients develop severe respiratory injury symptoms, which can be fatal . HBoV1 can be detected in fecal samples , blood samples , urine , cerebrospinal fluid , river water and sewage , indicating that HBoV1 may be associate with a variety of diseases. Current in vitro studies modeling tissue-like airway Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: Text: Human bocavirus 1 , which belongs to family Parvoviridae, was firstly identified in respiratory secretions of children with respiratory tract disease in 2005 . HBoV1 has been confirmed as an important respiratory pathogen and is found in respiratory infections in children and adults worldwide. The prevalence of HBoV1 nucleic acid detection varies from 1.5 to 33% in patients with acute respiratory illness , according to different studies . Serological and nucleic acid test results are generally consistent , showing HBoV1 infection is very common. HBoV1 can cause both upper respiratory illness and lower respiratory illness . Infection with HBoV1 Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: unknown and more research is needed to determine this. The characteristics of the HBoV1 infection are likely to be a good model for studying the effects of co-infections. Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region\nPassage: Two hundred forty-eight of 11,399 patients tested positive for HBoV1 infection. Of the HBoV1-positive patients, 112 were co-infected with other pathogens, most frequently with RSV . The median age was 1 year . The male-to-female ratio was 2.54:1 in HBoV1-positive patients and 1.81:1 in HBoV1-negative patients .", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: Using Systematic Reviews A systematic review consists of an examination of all of the primary studies on a topic, which includes searching for, collating, and assessing the studies, to establish conclusive evidence about a topic . The Cochrane Collaboration is an international body that produces systematic reviews of primary research at the highest standard, and as such, this is a commonly accepted definition of systematic reviews. Evidence-informed public health advocates the incorporation of the best available scientific evidence into decision making . Review level evidence is an important part of evidence-informed public health decision making, since reviews synthesize the results Title: Cochrane Systematic Reviews of Chinese Herbal Medicines: An Overview", "Passage: based on how well the review scored on the first 9 questions. Title: Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis\nPassage: in study design. Nonetheless, there was evidence of consistency across studies, as the themes identified were supported by evidence from all three emergency services, suggesting that the findings of the review are likely to be relevant to all types of EDC operatives. Title: Cochrane Systematic Reviews of Chinese Herbal Medicines: An Overview", "Passage: As broad questions of reviews may be addressed by large sets of heterogeneous studies, the data synthesis may be particularly challenging. In our study, 9 reviews pooled the results of different herbs, which did not identify potentially important differences in effects across different interventions. Systematic reviews can, but do not have to use meta-analysis when combining data from primary studies, prior to conducting a meta-analysis, reviewers should examine the consistency of the interventions. It is recommended that the data of each intervention should be analyzed and presented separately if several different interventions for the same condition were tested in one", "Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China\nPassage: case the patient load exceeds the hospital capability of the IDH, new IDHs should be considered either by building a temporary new IDH or reconstructing an existing hospital. Wuhan, the epicenter of the outbreak, is racing against time to build two specialized hospitals for nCoV patients, namely Huoshenshan and Leishenshan hospital, whereas a different strategy has been undertaken in Shenzhen city by reconstructing an existing hospital to become an IDH with capability of 800 beds. Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020\nPassage: cases as of 17 January 2020 . The former study from the United States assumes that the catchment area population is 10 million . Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: development and a candidate vaccine was ready for initial laboratory testing. Currently Chinese health authorities are building a 1000 bed hospital in Wuhan in 10 days. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: infected patients of whom13,701 are under medical observation . Outside China, 44,067", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: . Pneumonia deaths decreased from 1.8 million in 2000 to 900,000 in 2013 . These data do not reflect the full impact of increasingly widespread use of pneumococcal conjugate vaccine in low-and middle-income countries because the incidence of pneumonia and number of deaths are likely to decrease still further as a result of this widespread intervention . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The overall burden of childhood pneumonia has been reduced substantially over the last decade, despite an increase in the global childhood population from 605 million in 2000 to 664 million in 2015 . Recent data suggest that there has been a 25% decrease in the incidence of pneumonia, from 0.29 episodes per child year in low-and middle-income countries in 2000, to 0.22 episodes per child year in 2010 . This is substantiated by a 58% decrease in pneumonia-associated disability-adjusted life years between 1990 and 2013, from 186 million to 78 million as estimated in the Global Burden of Disease study Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: per million between 1981 and 1998, to 66 per million in 2005 . These trends have been reversed since the introduction of pneumococcal conjugate vaccination-13. Data from the United States suggest that empyema decreased by 50% in children younger than 5 years ; similarly, data from the United Kingdom and Scotland showed substantial reduction in pediatric empyema following pneumococcal conjugate vaccination-13 introduction . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Improved access to health care, better nutrition and improved living conditions might contribute to further decreases in childhood pneumonia burden. The WHO Integrated Global Action Plan for diarrhea and pneumonia highlights many opportunities to protect, prevent and treat children . Breastfeeding rates can be improved by programs that combine education and counseling interventions in homes, communities and health facilities, and by promotion of baby-friendly hospitals . Improved home ventilation, cleaner cooking fuels and reduction in exposure to cigarette smoke are essential interventions to reduce the incidence and severity of pneumonia . Prevention of pediatric HIV is possible by providing interventions", "Title: Tumor Restrictions to Oncolytic Virus\nPassage: On a cellular level, virus replication is controlled by antiviral defense molecules , which in turn are primarily controlled by type I IFN signaling. In addition to classical type I IFN-or cytokine-induced antiviral signaling, tumors may employ other antiviral defense mechanisms. For example, stromal cells may secrete peptides with antiviral properties called defensins . The defensins are amphiphatic and typically 29-42 amino acids in length and interfere with viruses by physically binding to and disrupting virus particles and/or by inducing antiviral responses in target cells via pattern recognition receptors. At least oral squamous cell carcinomas were found to overexpress defensins Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: of IFN-a may act more as a rapidly inducible immune response following virus invasion than as a constitutive secretion of functional IFN-a protein. Nonetheless, as hypothesized, PaKiT01 cell lines were by far the most antiviral of any in our study-with initial antiviral rates estimated several orders of magnitude higher than any others in our study, under either induced or constitutive assumptions . RoNi/7.1 cells displayed the second-most-pronounced signature of immunity, followed by Vero cells, for which the initial antiviral rate was essentially zero even under forced assumptions of induced or constitutive immunity . Title: Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C", "Passage: Mammalian cell expression systems are favored because they are capable of performing appropriate complex mammalian-type PTMs and authentic assembly of recombinant proteins . Various HCV VLPs vaccine candidates have been successfully produced in mammalian cells including Chinese hamster ovary , Huh-7cells, and human embryonic kidney 293T cells . Immunization with recombinant HCV envelope glycoproteins produced in mammalian cells protected chimpanzees more effectively compared to those produced in yeast or insect cells after challenge with a homologous HCV isolate . Similarly, mammalian cellderived recombinant envelope proteins have been reported to bind strongly to human cells compared to those produced in yeast Title: Natural killer cells act as rheostats modulating anti-viral T cells", "Passage: gift of L. Lanier, and 200 \u00b5g was injected i.p. at the time of infection. Mice were depleted of T cells by i.p. injection of either 100 \u00b5g anti-CD4 or 50 \u00b5g anti-CD8 produced by Bio-X-Cell at day \u22121 and day +3 of infection. In some experiments, mice were inoculated i.p. with 1.5\u00d710 7 PFU of PV, 8\u00d710 5 PFU of MHV strain A59, 1\u00d710 6 PFU of VV strain Western Reserve, 1\u00d710 6 PFU of Smith strain MCMV, or 200 \u00b5g of polyI:C .", "Title: The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care\nPassage: Molecular assessment is critical not only to establish a diagnosis but also to allow participation in clinical trials of therapeutic treatments that are designed for a specific set of variants or variant types. An extensive diagnostic workup involving protein studies on muscle biopsy may be used to narrow the number of single genes to be tested, but many patients never are specifically diagnosed. Comprehensive approaches to expedite molecular diagnosis now include NGS-based panel testing for sequence analysis of all disease-associated genes in a single analysis. Heritable Cancer Panel Genomic testing for familial cancer syndromes has become routine over the past Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: There are eleven studies that focus on SARS-CoV diagnostic testing . These papers described diagnostic methods to detect the virus with the majority of them using molecular testing for diagnosis. Comparison between the molecular test and serological test showed that the molecular test has better sensitivity and specificity. Hence, enhancements to the current molecular test were conducted to improve the diagnosis. Studies looked at using nested PCR to include a pre-amplification step or incorporating N gene as an additional sensitive molecular marker to improve on the sensitivity . Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: the samples and the techniques more appropriate for them. Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: The 16 265 biochemistry/haematology and microbiology tests comprised 71.1% of the 22 876 other tests ordered for patients in the study. After adjusting for baseline characteristics, the proportions of patients for whom full blood count, electrolyte/urea/creatinine levels, liver function, or C-reactive protein were assessed were similar, as were the proportions for urine microscopy, culture and sensitivity tests. Significantly fewer blood culture, blood gas, sputum culture, and respiratory bacterial and viral serology tests were ordered for patients in the rapid PCR group . Information, figure 1 ).", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: . Intriguingly, NYVAC may have an advantage for use as an influenza vaccine vector, because immunization with this vector induces weaker vaccine-specific immune responses compared to other poxvirus vaccines, a feature that may address the concerns surrounding preexisting immunity . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: The NYVAC vector is a highly attenuated vaccinia virus strain. NYVAC is replication-restricted; however, it grows in chick embryo fibroblasts and Vero cells enabling vaccine-scale production. In non-permissive cells, critical late structural proteins are not produced stopping replication at the immature virion stage . NYVAC is very attenuated and considered safe for use in humans of all ages; however, it predominantly induces a CD4 + T cell response which is different compared to MVA . Both MVA and NYVAC provoke robust humoral responses, and can be delivered mucosally to induce mucosal antibody responses . There has been only limited exploration Title: Virus-Vectored Influenza Virus Vaccines\nPassage: of NYVAC as a vaccine vector for influenza virus; however, a vaccine expressing the HA from A/chicken/Indonesia/7/2003 was shown to induce potent neutralizing antibody responses and protect against challenge in swine . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is strong safety and efficacy data for use of NYVAC or MVA-vectored influenza vaccines, preexisting immunity remains a concern. Although the smallpox vaccination campaign has resulted in a population of poxvirus-na\u00ef ve people, the initiation of an MVA or NYVAC vaccination program for HIV, influenza or other pathogens will rapidly reduce this susceptible population. While there is significant interest in development of pox-vectored influenza virus vaccines, current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains. This would likely limit the use and/or efficacy of poxvirus-vectored influenza virus vaccines for regular and seasonal use", "Title: Insights into the transmission of respiratory infectious diseases through empirical human contact networks\nPassage: In fact, the influenza spreading behavior can be clearly divided into two categories: in the US schools, disease outbreak appears to be relatively strong and early ; in the schools of SCAU, USTB as well as FRPS, a considerably low transmission was observed . Title: Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens", "Passage: Transmission dynamics are strongly dependent on the context in which that transmission occurs. In our model, the important factors governing these contexts are their physical properties, e.g. the degree to which surfaces can be contaminated by shedding events and behavioral properties e.g., how frequently those fomites are touched. It is important to note that interpreting a transmission venue in our framework depends on the method of shedding. For example, norovirus is primarily shed through contaminated fecal matter and vomiting. These shedding events may occur at a lower rate than coughing episodes that can spread respiratory pathogens and are also more Title: Insights into the transmission of respiratory infectious diseases through empirical human contact networks\nPassage: describes the duration of the disease spread. Title: Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens", "Passage: three general types of venues: subways, offices, and schools/daycares.", "Title: A method of processing nasopharyngeal swabs to enable multiple testing\nPassage: A total of 25 samples were sequenced with an average of 63 million paired-reads per sample. All 25 RNA samples were within the expected purity ratio of \u22651.8. The mean RNA yield was 772.3 ng. All RNA samples used in this study had an RNA Integrity number of \u22656.0. On average 93% of reads had a quality score of 30 of higher. Samples were mapped to the Hg19 Human genome build with an average of 97% mapping rate . Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: Of the 29 swabs received, 18 had a corresponding research swab that was positive for a respiratory pathogen. Seven corresponding self-swabs were concordant with the positive research swabs for influenza, and eight corresponding self-swabs were concordant with the research swab for noninfluenza pathogens . The kappa statistic between research and self-swab was 0.84. There were no differences in demographic variables, including education level or days between drop-off and receipt of swabs, among participants whose self-and research-staff obtained swabs correlated versus those whose swabs did not correlate . Of the self-swab samples that had a corresponding positive research swab, the longest Title: Pilot study of participant-collected nasal swabs for acute respiratory infections in a low-income, urban population", "Passage: To assess feasibility, we determined the proportion of households agreeing to perform the self-swab, the proportion returning the swab, and the number of days elapsed between when the participants received the kit and when the swab arrived in the laboratory. All swabs obtained by research staff were analyzed by a commercially available multiplex reverse transcription polymerase chain reaction assay according to the manufacturer's instructions . The assay has a limit of detection of 1-200 tissue culture infective dose 50/mL for influenza, and an LOD of 4-30,000 TCID50/mL for non-influenza viral pathogens, of which only rhinovirus/enterovirus has an LOD of more Title: A method of processing nasopharyngeal swabs to enable multiple testing", "Passage: We processed 163 samples for 16S rRNA gene amplicon sequencing. We were able to recover on average >16,000 sequences per sample, accounting for a total of 2,646 OTUs. When rarefied to10,000 sequences per sample in order to capture most of the samples and normalize depth of coverage, rarefaction curves indicated that the NP swabs and sequencing depth adequately sampled microbial species richness . As expected, when more sequences were analyzed per sample, the lines start to plateau . This indicates that even though more sequences were analyzed, few new species were detected. Furthermore, no significant difference was observed in species", "Title: Viral factors in influenza pandemic risk assessment\nPassage: . At the same time, passage bias mutations are assumed to increase fitness of the strain in the respective species and are often necessary to grow in culture at all. Therefore, sites associated with isolates passaged in mammalian cultures vs. those passaged in embryonated hen's eggs have the potential to further identify sites associated with mammalian or human adaptation. Metadata can also help to point to individual amino acids associated with human adaptation. For example, one proposed computational approach is to find potentially zoonotic human-isolated sequences when the majority of their database hits from preceding years were of animal origin. Title: Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution", "Passage: MARV, it makes sense that virus has evolved its genomic features to a stable level in order to better adapt to its primary host's environment. It has also been recently suggested that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this hostvirus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant Title: Viral factors in influenza pandemic risk assessment", "Passage: Ultimately, it would be valuable to develop a simple screen to assess the ability of a viral polymerase to support replication and transmission in humans. This phenotype is influenced by at least 4 different viral genes and involves interactions with several different human host factors. If all the relevant host factors were enumerated, one could imagine quickly converting sequence information into an assay that tested for interactions that should support activity. Along these lines the recent description of a host factor, ANP32A that differs between flighted birds and mammals and explains the poor activity of avian polymerase in mammalian cells Title: Viral factors in influenza pandemic risk assessment", "Passage: host factor or enhance its ability to repel a restriction factor . Recently a host factor, ANP32A, that differs between mammals and flighted birds was shown to be a cofactor of the influenza polymerase, and the species specific difference could explain the inefficient function of avian virus polymerase and the stringent selection for the 627Glu->Lys adaptive mutation in mammals .", "Title: Viral Interference and Persistence in Mosquito-Borne Flaviviruses\nPassage: The Flaviviridae family includes approximately 80 members divided into four genera: Flavivirus, Pestivirus, Pegivirus, and Hepacivirus. The Flavivirus genus can be further divided into four categories: mosquito-borne, tick-borne, no known vector , and insect-specific viruses . Mosquitoand tick-borne flaviviruses, including Dengue , Japanese encephalitis virus , Yellow fever virus , Saint Louis encephalitis virus , West Nile virus , Murray Valley encephalitis virus , and tick-borne encephalitis virus , are important pathogens responsible for human diseases, such as encephalitis, fever, and haemorrhagic fever. Title: Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization", "Passage: All viruses in the genus Flavivirus possess a single-stranded, positive-sense RNA genome of approximately 11 kb . The genome usually encodes a single open reading frame that is flanked by 5' and 3' untranslated regions of ~100 and ~400-700 nt, respectively . The ORF encodes a large polyprotein that is co-and post-translationally cleaved to generate three structural proteins, designated the capsid , premembrane/membrane and envelope proteins, and seven nonstructural proteins in the gene order: 5'-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-2K-NS4B-NS5-3' . The genomes of some flaviviruses appear to encode an additional protein as a consequence of ribosomal frameshifting as discussed later in this review. Title: In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions", "Passage: The emergence and resurgence of human viral pathogens can be traced to a complex variety of causes including increased urbanization, human contact with animal reservoirs, a decrease in effective public health systems, and the spread of insect vectors that disseminate some viral infections . Flaviviruses are a genus in the Flaviviridae family and include important emerging and resurgent human pathogens such as dengue virus , West Nile virus , tick-borne encephalitis virus and yellow fever virus . Flaviviruses are transmitted by insects such as mosquitoes and ticks, and can cause severe human diseases characterized by encephalitis, meningitis, and hemorrhages . Title: Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization", "Passage: Despite their similar genomic organizations, flaviviruses possess fundamental differences in their host ranges and transmissibilities. Most recognized flaviviruses are transmitted horizontally between hematophagous arthropods and vertebrate hosts and are therefore considered to be dual-host viruses. Dual-host flaviviruses can be further divided into mosquito/vertebrate and tick/vertebrate viruses. Examples of mosquito/vertebrate flaviviruses include dengue virus , yellow fever virus, Japanese encephalitis virus and West Nile virus , all of which are human pathogens of global concern . Flaviviruses of localized public health concern include St Louis encephalitis virus and Murray Valley encephalitis virus . Tick/vertebrate flaviviruses associated with serious human disease include", "Title: Bibliometric analysis of publications on Campylobacter: (2000\u20132015)\nPassage: attached for those who are interested . Title: Outdoor environments and human pathogens in air\nPassage: At the first two meetings, participants were given a topic and asked to prepare a one-page literature review to support their presentations; each topic was assigned to two participants from different disciplines in order to ensure cross-disciplinarity of the discussion. These presentations now form the core of our review, and all the discussions from all the meetings were recorded. We have conducted an extended literature search and review to ensure that the content is representative, comprehensive and connected to the five main areas arranged below. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis", "Passage: Several limitations exist in our study. First, we characterised the knowledge structures generated by a large number of articles published in major medical journals that are included in the WoS database. However, our results are limited to a subset of all clinical-trial-related articles published in 40 leading medical journals. We suspect that these articles represent those that have great implications for clinical practice and that are relevant to clinical practice guidelines and healthcare regulators. Although the publication production analysed has been drawn from an exhaustive analysis of the biomedical literature, possibly, the search missed some relevant articles . Some reports Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: how the characteristics of the field change over time will be interesting to see.", "Title: Artificial MicroRNA-Mediated Inhibition of Japanese Encephalitis Virus Replication in Neuronal Cells\nPassage: Exogenous miRNAs may be sensitive to interferon response and can exhibit substantial antiviral effect by inducing interferon-stimulated genes . We checked four ISG expression in N2a cells after transfecting amiRNAs. We observed a variable level of ISG expression upon transfection of amiRNA #1 and amiRNA #5. However, no change in expression level of ISGs was evident in amiRNA #2-transfected cells. Title: MiR-23a Facilitates the Replication of HSV-1 through the Suppression of Interferon Regulatory Factor 1", "Passage: MicroRNAs are small, ,22-nucleotides, RNA molecules that were first discovered in Caenorhabditis elegans and are expressed in a wide range of eukaryotic organisms . Mammalian miRNAs can bind to imperfectly complementary sites in the 39 noncoding regions of target mRNAs and thereby act as specific post-transcriptional inhibitors of mRNA function . The gene-silencing effect triggered by miRNAs may serve major function at two levels to modulate host-virus interactions . On the one hand, cellular miRNAs target viral mRNAs in the defense against viral infection . Secondly, several viral miRNAs regulate the expression of cellular factors that are involved in cellular Title: HCV-Induced miR-21 Contributes to Evasion of Host Immune System by Targeting MyD88 and IRAK1", "Passage: MicroRNAs are an abundant class of highly conserved small non-coding RNAs. They function primarily by binding to the 39 untranslated region of target mRNAs to achieve post-transcriptional regulation of gene expression . Many miRNAs have been reported to regulate a wide range of biological processes, including development , cell differentiation , proliferation, and apoptosis . Many miRNAs, including miR-146 , miR-155 , miR-98, and let-7 , participate in innate and adaptive immune responses . miR-21 was found to be more strongly expressed in HCC specimens than in non-tumorous tissues , and participates in HCC development by regulating the phosphatase and Title: miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1", "Passage: investigate whether these new miRNA candidates were silenced by epigenetic modifications, we detected the miRNA expression in RAW cells upon treatment with HDAC inhibitor Trichostatin A . A total of 24 new miRNA candidates were upregulated upon TSA treatment, and miR-1-1 was used as positive control 28 . ChIP assays on the potential promoter of representative candidates , using two sets of qPCR primers spanning the promoter , showed upregulation of histone H3 acetylation in TSA treatment group , miR-1-1 was used as positive control.", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Previous studies have shown that the extent of rice cultivation is a risk factor, mainly due its association with free ranging ducks acting as scavengers . We used percentage of land under rice cultivation as a measure of extent. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Previous studies have shown that the extent of rice cultivation is a risk factor, mainly due its association with free ranging ducks acting as scavengers . We used percentage of land under rice cultivation as a measure of extent. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: Rice cropping intensity is also a known risk factor . We used the mean number of rice crops per year as a measure of intensity. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Rice cropping intensity is also a known risk factor . We used the mean number of rice crops per year as a measure of intensity.", "Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: of this manuscript. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: 9, 2019. Title: Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey", "Passage: 9, 2019. Title: Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey\nPassage: The results and implications of this study need to be considered in light of the investigation's limitations. Although the newspapers analyzed in this investigation are highly circulated, they represent only a small proportion of all daily, paid North American newspapers. Additionally, we only reviewed the articles of 4 largely circulated newspapers -it is not clear whether similar trends were reported in other newspapers, on radio, television and through other online sources. To assess the impact on such media reports on the public would require prospective studies with large numbers of people, a study beyond the scope of the present investigation. Title: Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey\nPassage: for evaluating whether the clinical severity of these injuries is being appropriately communicated.", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: The findings may help to explain why bats are often the source for viruses that are deadly in humans. Learning more about bats' antiviral defenses and how they drive virus evolution may help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. More studies are needed in bats to help these efforts. In the meantime, the experiments highlight the importance of warning people to avoid direct contact with wild bats. up resource supply of infection-susceptible host cells, were first developed for HIV but have since been applied to other chronic infections, including Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: countered by the virus spreading more quickly from cell to cell. This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures like humans are not. Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: Bats have a suite of antiviral defenses that keep the amount of virus in check. For example, some bats have an antiviral immune response called the interferon pathway perpetually switched on. In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm, include the loss of certain genes that normally promote inflammation. However, no one has previously explored how these unique antiviral defenses of bats impact the viruses themselves. Now, Brook et al. have studied this exact question using bat cells grown in the laboratory. Title: Bat Astroviruses: Towards Understanding the Transmission Dynamics of a Neglected Virus Family", "Passage: the only flying mammals, bats have evolved special anatomical and physiological characteristics. Several of them appear to be relevant for their role as reservoir hosts of viral agents. As opposed to the reduced body temperature when resting, the body temperature of bats may increase during flight to above 40 \u2022 C, which is thought to mimic a fever . On the other hand, the reduced body temperature and low metabolic rate during hibernation or torpor have been discussed to negatively affect the efficient immune response to infections. This may impair viral clearance, and therefore, by transmission to juvenile bats born", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Middle East respiratory syndrome was first reported in September 2012 in Saudi Arabia, following isolation of MERS-CoV from a male patient who died months earlier from severe pneumonia and multiple organ failure . In the 8 years since then, there have been more than 2494 confirmed cases of MERS resulting in upwards of 858 deaths globally . While 27 countries have reported cases of MERS, approximately 80% of confirmed cases originated in Saudi Arabia . To date, all known cases of MERS can be linked to travel or residence in countries along the Arabian Peninsula-that is, Bahrain; Iraq; Iran; Israel, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Text: An email from Dr Ali Mohamed Zaki, an Egyptian virologist working at the Dr Soliman Fakeeh Hospital in Jeddah in the Kingdom of Saudi Arabia announced the first culture of a new coronavirus to the world. The email was published on the website of the professional emerging diseases network on 20 th September 2012 and described the first reported case, a 60 year old man from Bisha in the KSA. This information led to the rapid discovery of a second case of the virus, this time in an ill patient in the United Kingdom, who had been transferred from Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Text: A respiratory viral disease caused by the Middle East Respiratory Syndrome CoronaVirus was first isolated in 2012, in a 60-year-old man who died in Jeddah, KSA due to severe acute pneumonia and multiple organ failure . Since then, 27 countries have reported the presence of this virus, including the 12 countries of the Eastern Mediterranean region. Several outbreaks have occurred in multiple countries including Saudi Arabia, the United Arab Emirates and the Republic of Korea . Recent fatality rate of 21% . Very limited evidence is available for exploring the epidemiology of this virus among the pediatric population .", "Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires\nPassage: and development in these patients . Finally, Ab studies have been pivotal in demonstrating the clonal origin of multiple myeloma and more recently, sequencing technologies to define a patient's Ab repertoire have been applied clinically for disease detection and assessment of therapeutic response in myelomas as well as leukemias . Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires\nPassage: As we will discuss, the techniques outlined above have been applied to Bmem subsets, allowing an improved understanding of their development and differentiation during specific diseases and post-vaccination. Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires", "Passage: In addition to infectious diseases, the analysis of B cell repertoires has improved our ability to detect immune system disorders and to elucidate the possible mechanisms causing them. For example, rheumatoid arthritis is a systemic autoimmune disease that often involves the production of anti-citrullinated protein Abs. Ab sequencing in RA patients has defined autoantibody specificities and provided insights into clinical disease and the mechanisms leading to breaks in tolerance and increased pro-inflammatory activity . In common variable immune deficiency, analysis of Ig H chain gene rearrangements demonstrated abnormal VDJ rearrangement and CDR3 formation, suggesting early differences in B cell selection Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: rearrangement during B cell differentiation was responsible for antibody diversification . The subsequent explosion of available monoclonal antibodies led to revolutionary diagnostic, therapeutic, and research reagents to distinguish different types of immune cells . Together, these discoveries have allowed us to probe humoral immunity at the level of the antigen-specific B cell.", "Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: The most common viruses detected were RSV and rhinovirus accounting for almost 60% of all cases. Both viruses were reported previously by others as the major aetiology for respiratory viral infections in young children with rhinoviruses being recognized increasingly for their role in lower respiratory tract infections . Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: In our study, leukocyte count was used as an indicator of inclusion criteria and it probably affected the positive rate. Viruses not considered in the study, for example coronaviruses, would underestimate the positive rate. Most studies showed that RSV or HRV was the most prevalent viruses in children with viral respiratory tract infection. 1 In this study, IAV was the most frequently detected respiratory virus, followed by RSV and HRV. IAV outbreak in 2009 could explain this shift. Data showed that about 60% of IAV infections were detected during the outbreak period. Studies showed that the H1N1 outbreak could change Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Viral heterogeneity associated with ARIs is well established . In the past, human rhinovirus has been identified as the virus most frequently associated with respiratory illness with 30-50% of infections annually on average, and up to 80% of upper respiratory infections during the autumn outbreaks . After HRVs, coronaviruses , influenza, respiratory syncytial virus and parainfluenza viruses are the next most frequent. Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: Rhinoviruses are responsible for more than one-half of upper respiratory tract infections and they are considered to be among the most frequent infectious agents in humans worldwide . Most cases of RV infections are benign, self-limited cold-like illnesses. However, these viruses have been also identified as the causal agent of severe pneumonia in the elderly and immunocompromised patients, as well as exacerbations of chronic obstructive pulmonary disease and asthma. At present, no efficient antiviral treatment, vaccines, or other preventive measures exist against these particularly frequent pathogens . In addition to the significant associated clinical morbidities, the economic impact of RV-related", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: Adenovirus vectors are attractive as vaccine vectors because their genome is very stable and there are a variety of recombinant systems available which can accommodate up to 10 kb of recombinant genetic material . Adenovirus is a non-enveloped virus which is relatively stable and can be formulated for long-term storage at 4 \u00b0C, or even storage up to six months at room temperature . Adenovirus vaccines can be grown to high titers, exceeding 10 1\u00b0 plaque forming units per mL when cultured on 293 or PER.C6 cells , and the virus can be purified by simple methods . Adenovirus vaccines Title: Virus-Vectored Influenza Virus Vaccines", "Passage: There are 53 serotypes of adenovirus, many of which have been explored as vaccine vectors. A live adenovirus vaccine containing serotypes 4 and 7 has been in use by the military for decades, suggesting adenoviruses may be safe for widespread vaccine use . However, safety concerns have led to the majority of adenovirus-based vaccine development to focus on replication-defective vectors. Adenovirus 5 is the most-studied serotype, having been tested for gene delivery and anti-cancer agents, as well as for infectious disease vaccines. Title: Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine", "Passage: Viral vectored vaccines are known to be an effective mechanism to induce cellular responses compared with subunit vaccines and can induce protective T cell responses against intracellular pathogens . Recombinant viruses are excellent vehicles for vaccine delivery as viral proteins can act as potent adjuvants and can directly infect antigen-presenting cells . Adenoviruses are highly attractive vectors for human vaccination as they possess a stable genome which prevents inserts of foreign genes from being deleted and they can infect large numbers of cells without any evidence of insertional mutagenesis . Title: Viral vector-based influenza vaccines", "Passage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview", "Title: Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition\nPassage: Purification of DNA using denaturing PAGE . 20% denaturing polyacrylamide gels were cast using 5 to 25\u00b0C at the rate of 0.15\u00b0C/min using a thermal cycler . Partial DNA star complexes were made by following the same ratios listed for the full star but the species of each group were adjusted depending on number of triangles as elaborated below. After formation, all DNA complexes were stored at 4\u00b0C overnight for downstream use. Title: Sequence specific visual detection of LAMP reactions by addition of cationic polymers", "Passage: Commercially available PEI was used without further purification. The average molecular weight of PEI used was 600, 1,800, and 10,000. In this study, the concentration of the PEI aqueous solution is expressed as the concentration of the monomer unit . The PEI stock solution was prepared by dissolving 4.6 g of PEI in 50 mL of deionized distilled water in a graduated cylinder. At the time of use, the stock solution was diluted with water to the desired concentration. Title: Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S-Nitroso-N-acetyl-d-penicillamine\nPassage: into the polymer solution. After 5 min of stirring, the solutions were cast in Teflon rings on a Teflon surface, and the films were allowed to dry overnight under ambient conditions. Small film disks were cut from the parent films and Title: Proteomic Analysis of the Vitreous following Experimental Retinal Detachment in Rabbits", "Passage: the use of a MultiTemp III Thermostatic Circulator . Before the second-dimension sodium dodecyl sulfate polyacrylamide gel electrophoresis , the IPG strips were equilibrated firstly for 10 min with gentle agitation in 20 mL of equilibration solution Tris-HCl, pH 6.8, 6 M urea, 30% glycerol, 1% SDS, and 0.05% DTT) and secondly using 4.5% iodoacetamide and bromophenol blue. The IPG strips were then transferred to 12% polyacrylamide gels for electrophoresis, which was performed at a maximum voltage of 50 V for approximately 20 h to separate the proteins vertically on the basis of molecular mass.", "Title: Contamination during doffing of personal protective equipment by healthcare providers\nPassage: Finally, the study protocol was not identical to 2014 CDC guidelines. It excluded aprons, leg covers, and tape seals between parts of the gear. The donning and doffing procedures refer to Tables 3 and 4 . This could be the reason that donning and doffing procedures were finished in very short intervals. Title: Contamination during doffing of personal protective equipment by healthcare providers", "Passage: A demographic survey was performed with all participants. The survey also included questions on job experience and previous training with PPE. During a simulation study, two separate cameras with high-density capability were set up at an approximate 120 degree angle to document the process. All processes were videotaped during PPE donning and doffing. Afterward, a trained examiner reviewed all video recordings and coded timer intervals and errors. Time stamps were determined according to a 2014 CDC protocol. Each procedure was initiated when the participant picked up the equipment. The procedure ended when the next procedure was initiated. Errors were determined Title: Healthcare Workers\u2019 Strategies for Doffing Personal Protective Equipment", "Passage: We found that response patterns for doffing strategies varied across PPE types and designs. In the mask simulation scenario, the tension between safety and expediency tended to be most pronounced for the surgical mask with ties . For example, several participants tried to untie the mask because they thought it would be safer to remove that way, though some admitted that in practice they would probably rip the mask off. However, most participants described using both strategies to doff gowns and typically did not see much conflict or tension between them. While ripping gowns was not perceived as inherently unsafe, Title: Healthcare Workers\u2019 Strategies for Doffing Personal Protective Equipment", "Passage: 1 knot, not tying the fasteners while donning, or simply ripping the PPE off rather than untying the fasteners. However, ripping off PPE was not easy with certain designs , particularly the masks with bands and the gowns with thicker belts. Some participants also found the gown with the tape-tab neck closure harder to rip off in a predictable and controlled way. While gloves were not associated with the barriers described above, several participants described difficulty safely doffing the glove on the second hand . PPE fit was also a barrier to doffing all types of PPE , typically when", "Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection\nPassage: Moreover, the efficacy and toxicity of manidipine were monitored in vivo, with manidipine demonstrating effective antiviral activity with favorable biocompatibility. However, the dose used in this study was higher than the dose typically used clinically, representing one of the scenarios most commonly encountered in drug repurposing . As manidipine was approved for use for the long-term treatment of hypertension , pulse-dose treatment with manidipine over the shorter period of time required for the treatment of virus infection might be relatively safe. Moreover, use of a combination of manidipine with other Ca 2\u03e9 inhibitors might improve its therapeutic efficacy, reduce its Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: Moreover, the efficacy and toxicity of manidipine were monitored in vivo, with manidipine demonstrating effective antiviral activity with favorable biocompatibility. However, the dose used in this study was higher than the dose typically used clinically, representing one of the scenarios most commonly encountered in drug repurposing . As manidipine was approved for use for the long-term treatment of hypertension , pulse-dose treatment with manidipine over the shorter period of time required for the treatment of virus infection might be relatively safe. Moreover, use of a combination of manidipine with other Ca 2\u03e9 inhibitors might improve its therapeutic efficacy, reduce its Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: In vivo efficacy of manidipine. As manidipine exhibited the strongest inhibitory activities on JEV replication as well as ZIKV infection when its activities were compared with those of the five hit drugs , we further examined the protective effect of manidipine against JEV-induced lethality in a mouse model. As anticipated, mice in the JEV-infected vehicle-treated group started to show symptoms, including limb paralysis, restriction of movement, piloerection, body stiffening, and whole-body tremor, from day 5 postinfection. Within 21 days postinfection, most mice in the JEV-infected group succumbed to the infection, with the mortality rate being 73% . Manidipine treatment following Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: In vivo efficacy of manidipine. As manidipine exhibited the strongest inhibitory activities on JEV replication as well as ZIKV infection when its activities were compared with those of the five hit drugs , we further examined the protective effect of manidipine against JEV-induced lethality in a mouse model. As anticipated, mice in the JEV-infected vehicle-treated group started to show symptoms, including limb paralysis, restriction of movement, piloerection, body stiffening, and whole-body tremor, from day 5 postinfection. Within 21 days postinfection, most mice in the JEV-infected group succumbed to the infection, with the mortality rate being 73% . Manidipine treatment following", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: In the mid-1980s, the principle of modifying the filamentous phage genome to display polypeptides as fusions to coat proteins on the virion surface was invented by Smith and colleagues . Based on the ideas described in Parmley and Smith , groups in California, Germany, and the UK developed phage-display platforms to create and screen libraries of peptide and folded-protein variants . This technology allowed, for the first time, the ability to seamlessly connect genetic information with protein function for a large number of protein variants simultaneously, and has been widely and productively exploited in studies of proteinprotein interactions. Many excellent Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: In the mid-1980s, the principle of modifying the filamentous phage genome to display polypeptides as fusions to coat proteins on the virion surface was invented by Smith and colleagues . Based on the ideas described in Parmley and Smith , groups in California, Germany, and the UK developed phage-display platforms to create and screen libraries of peptide and folded-protein variants . This technology allowed, for the first time, the ability to seamlessly connect genetic information with protein function for a large number of protein variants simultaneously, and has been widely and productively exploited in studies of proteinprotein interactions. Many excellent Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: This phage can be easily manipulated due to its small genome. Therefore, these are the best-studied viruses and are extensively used in phage display technology. Large phage particles can be produced by the insertion of DNA into non-essential regions, are stable in extreme conditions, and can be produced in high amounts . Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Phage display technology has facilitated the production of protein libraries, which are formed with large numbers of phage particles displaying different molecules . Specific binder screening with biopanning allows the enrichment of the desired molecule . The first step is the incubation of the display library with an immobilized surface of the entire cell. The non-binding phages are then removed by extensive washing and the binders are eluted by acid or salt buffer. Then, binders are amplified using an appropriate bacterial host cell such as E. coli. To obtain highaffinity targets, up to five rounds of biopanning are performed .", "Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection\nPassage: the actual number of cases. The preadmission antibiotic therapy could underestimate the bacterial coinfection rates. Despite these limitations, we identified bacteria coinfection in 28% of our patients. Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: The bacterial coinfection rate of 28% amongst our H1N1 hospitalized patients was higher compared to other studies . A large laboratory-based study in the United States demonstrated comparable bacterial coinfection rates to our study with similarly very low frequency of viral copathogen detection . Whilst our finding concurred with several studies that showed H1N1 infections having a predilection for younger patients, patients > 50 years had higher risk of bacterial coinfection in our study. Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: A comparison between H1N1 patients with and without bacterial coinfection is shown in Table 2 . Although 90% of patients were < 50 years old, bacterial coinfection was more frequent in patients > 50 years . The presence of underlying comorbidity provided a suitable niche for bacterial coinfection . Although ICU admissions, mechanical ventilation, renal impairment, mortality and pneumonia were notably higher in patients with bacterial coinfection, they were not statistically significant. Other factors associated with bacterial coinfection in the univariate analysis were development of complications , liver impairment and supplemental oxygen requirement . Out of the 50 patients, 12 Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia\nPassage: nine patients of the mixed group.", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: fever-DR control room, and other patient examination access areas. The buffer zone includes Title: Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico\nPassage: The geographic universe in the study was divided in five areas , limited by four buffers. A circular buffer with 50 m radius around each participant's home limited the first area and three additional polygonal buffers were drawn according to the administrative limits for the locality, municipality and state. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: , semicontaminated , buffer , and clean areas Title: Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya", "Passage: of buffer zones. Other approaches could have been used including a hexagonal grid or larger clusters as was used in the study in Blantyre's urban slum area . These approaches will likely reduce, but not completely eliminate the edge effect. Moreover, in this study, there was a significant difference in the proportion of people correctly located at each health facility and not every participant was willing to complete the exercise. This suggests that the familiarity of the interviewers with the area, their ability to read and explain the maps to local populations, and the time they have or choose to", "Title: CDC Summary 21 MAR 2020,\nPassage: by a deceleration phase, during which there is a decrease in illnesses. Different countries can be in different phases of the pandemic at any point in time and different parts of the same country can also be in different phases of a pandemic. Title: CDC Summary 21 MAR 2020,\nPassage: Different parts of the country are seeing different levels of COVID-19 activity. The United States nationally is in the initiation phase of the pandemic. States in which community spread is occurring are in the acceleration phase. The duration and severity of each pandemic phase can vary depending on the characteristics of the virus and the public health response. Title: CDC Summary 21 MAR 2020,", "Passage: This is the first pandemic known to be caused by the emergence of a new coronavirus. In the past century, there have been four pandemics caused by the emergence of novel influenza viruses. As a result, most research and guidance around pandemics is specific to influenza, but the same premises can be applied to the current COVID-19 pandemic. Pandemics of respiratory disease follow a certain progression outlined in a \u201cPandemic Intervals Framework.\u201d Pandemics begin with an investigation phase, followed by recognition, initiation, and acceleration phases. The peak of illnesses occurs at the end of the acceleration phase, which is followed Title: The origins of the great pandemic", "Passage: Those who have chronicled the march of this pandemic have pointed to two distinct phases through which, during the year 1918, its incidence had moved. The first phase, which began in spring and lasted until August, was characterized by an acute onset and high fever. The illness was of short duration and fatalities were relatively few. Then followed, from the autumn onwards, a second and more destructive phase. It affected all ages and conditions, but as noted above its effects on young adults were particularly marked.", "Title: Preparedness of community-based organisations in biohazard: reliability and validity of an assessment tool\nPassage: its quality continuously. Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology\nPassage: \u2022 We rephrased the definitions in a way that for serologic confirmation the necessity for two samples is clearly apparent at the beginning of the phrase. Title: Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk", "Passage: Elements of the blood management system have been drawn to ISO 31000. Furthermore, processes such as recording, inter-professional communication, notification and disclosure have been applied in dealing with blood risk. Risk triggers and residual risk point to the relevance of hazard and liability discourses, especially as in other domains, use of the precautionary principle has been shown to trigger concerns and lower trust in governance structures ). So for the institution of precaution we must be clear on what we are managing, why and in what ways. For the Canadian blood system, a new procedure of providing reasons for recall Title: Preparedness of community-based organisations in biohazard: reliability and validity of an assessment tool\nPassage: questions were acceptable.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: to 36 hours post virus inoculation was associated with prevention of laboratory confirmed influenza and febrile illness as well as a reduction in viral titers, duration of shedding and symptoms. In total, safety data from 1092 patients after intranasal application of Zanamivir were published and no evidence for Zanamivir induced adverse events or increased frequencies of local nasal intolerance in comparison to placebo groups was found . Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: NI is needed for an effective treatment when the therapy starts 24 hpi is already known for Oseltamivir . Nonetheless, also data with much higher effective concentrations ) and with similar concentrations of Zanamivir ) were published as well. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: and weight loss. Mortality also includes mice that were sacrificed for ethical considerations when they had lost more than 25% of their initial body weight. We confirm the viral infection in these animals by necropsy and scoring of the lung inflammation. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: the upper respiratory tract . However, in its fully developed form influenza is an acute respiratory disease resulting in hospitalizations and deaths mainly among high-risk groups. Worldwide, annual epidemics result in about three to five million cases of severe illness, and about 250,000 to 500,000 deaths . For this reason WHO and CDC recommend antiviral treatment for any patient with suspected influenza who is at risk for influenza complications without previous laboratory confirmation.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: A rise in the cases termed asymptomatic ) resulted in a drop in the proportion of fatal cases during the Jeddah-2014 outbreak. Historically, such rises are consistent with changing definitions and laboratory responses and clinical management of a newly discovered virus infection that was first noted only among the severely ill. Upon follow-up, over three-quarters of such MERS-CoV RNA positive people did recall having one or more symptoms at the time, despite being reported as asymptomatic raising some question over the reliability of other reported data. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: families and healthcare settings . Clinical pictures of this infection varied from asymptomatic to mild respiratory symptoms to severe respiratory distress and death . Severe ailment can often cause respiratory catastrophes that need mechanical ventilation and support in ICUs across different healthcare settings . Studies have suggested an incubation period of 16 days with a mean of 5-6 days , while the median time until death is 11-13 days among severely ill patients . e gold standard test for the detection of this virus is real-time reverse-transcription polymerase chain reaction assays .", "Title: Preventing Emerging and Re-emerging Infections in the Eastern Mediterranean Region: Gaps, Challenges, and Priorities\nPassage: During 2010-2011, 31 out of 38 suspected disease outbreaks from 16 countries were confirmed after followup and verification. There were 5 major outbreaks, including chikungunya/dengue in Yemen, acute watery diarrhoea/ cholera in Somalia, viral conjunctivitis in Sudan and Lebanon, and dengue in Pakistan. Most of these were small outbreaks that were detected early and contained rapidly by the countries, with support from WHO country offices. Title: Extreme water-related weather events and waterborne disease", "Passage: of diarrhoeal disease outbreaks following natural disasters has previously been found to be higher in developing countries than in industrialized countries . Flooding events, for example, in high-income countries are rarely thought to result in epidemics of infectious disease or, where they do occur, they are thought to often be easily controlled and not widespread due to the rapid implementation of preventative measures . The scientific literature is also likely to be dominated by accounts of waterborne disease from higher-income countries, with greater academic and surveillance capacity. The amount and type of literature published on an extreme weather event, therefore, Title: Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II", "Passage: Finally, the outbreak from Kosovo deserves notice because this region is not as developed or as wealthy as most of the other countries studied. This outbreak was the largest identified for this review . Moreover, the hospital and mixed component of this outbreak had the second highest and highest initial reproductive rate, and the hospital component lasted 9 generations . This suggests that a smallpox outbreak in a less developed country with limited resources for healthcare, disease surveillance, and case isolation could be potentially more devastating than a bioterrorist attack in a Western/industrialized country . Title: The interconnected and cross-border nature of risks posed by infectious diseases", "Passage: It is instructive to provide a few examples of how such risks are interconnected in the context of infectious disease. Literally, hundreds of examples from around the world could have been selected. One study identified 335 events leading to an emerging infectious disease between 1940 and 2004, identifying numerous infectious disease 'hotspots' across the globe \u00c1 areas in which a disproportionately high number of disease emergencies have concentrated . Western Europe is identified as one such hotspot, and as the region with which the authors of this chapter are most familiar, the examples below will be slightly biased towards Europe.", "Title: Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study\nPassage: Of the 200 enrolled in this study, 25 patients were excluded from the analysis of the data. Of these, 21 patients had incomplete sampling and four patients met exclusion criteria. The characteristics on admission of the 175 patients included in our analysis study group are presented in Table 1 . Mean age was 62 years; roughly one-third had CAP, one-third had HAP, and one-third had VAP. The median hospital and ICU lengths of stay prior to enrolment were six days and nine days , respectively. Title: Effect of prior receipt of antibiotics on the pathogen distribution: a retrospective observational cohort study on 27,792 patients", "Passage: During the study period, a total of 48,692 patients were treated with various antibiotics, with samples taken from 27,792 patients within 2 days before or after starting antibiotic treatment. Among them, 19,868 of patient samples were taken before antibiotic therapy , and 7924 of patient samples were taken after antibiotic therapy . Title: Development of a tool to assess oral health-related quality of life in patients hospitalised in critical care\nPassage: There are no definitive criteria for the required sample size in a validation study of this kind. However, previous literature suggests that a sample size of 45 to 50 patients should be sufficient for the proposed analysis . Title: Participant retention practices in longitudinal clinical research studies with high retention rates", "Passage: Of the 19 participating studies, 13 were prospective cohort studies, 5 were RCTs, and 1 was a quasiexperimental study . Included studies had diverse patient populations, including victims of intimate partner violence, persons living with human immunodeficiency virus and acquired immunodeficiency syndrome , survivors of critical illness and other serious illnesses. The target sample size for studies ranged from 255-10,000. Actual sample recruitment at the time of interview ranged from 205 for the Community Aging in Place -Advancing Better Living for Elders study with older adults aging in place to 2528 for the Alzheimer's Disease Anti-Inflammatory Prevention Trial . Though", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Patients' specimens, including sputum, whole blood and serum samples, were collected upon admission and during hospitalization. Microbiological tests were performed at the Department of Infectious Disease and Clinical Microbiology in our center, and the detection methods used were described in our previous report . Common viruses causing respiratory illness were screened using a kit with 15 different viral assays. Serum samples were used for Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila antibodies. All patients had their HAdV-55 infection confirmed by RT-PCR assay. Partial sequences of the hexon gene were analyzed to type the phylogeny of HAdV-55 strains. The adenoviral load Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Patients' specimens, including sputum, whole blood and serum samples, were collected upon admission and during hospitalization. Microbiological tests were performed at the Department of Infectious Disease and Clinical Microbiology in our center, and the detection methods used were described in our previous report . Common viruses causing respiratory illness were screened using a kit with 15 different viral assays. Serum samples were used for Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila antibodies. All patients had their HAdV-55 infection confirmed by RT-PCR assay. Partial sequences of the hexon gene were analyzed to type the phylogeny of HAdV-55 strains. The adenoviral load Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: All patients had HAdV-55 viremia. In four of the five patients, it was first detected in endotracheal aspirate samples. The time between initial ETA sample collection of adenoviruses and positive results for HAdV-55 nucleic acid in the blood was 1 to 10 days . Virus DNA copies in ETAs were determined for all patients during their ICU stay. The viral load was higher than 1 \u00d7 10 8 copies in three patients and 1 \u00d7 10 4 in one patient. The viral load became negative in the only patient who survived. In the four patients who did not survive, DNA Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: All patients had HAdV-55 viremia. In four of the five patients, it was first detected in endotracheal aspirate samples. The time between initial ETA sample collection of adenoviruses and positive results for HAdV-55 nucleic acid in the blood was 1 to 10 days . Virus DNA copies in ETAs were determined for all patients during their ICU stay. The viral load was higher than 1 \u00d7 10 8 copies in three patients and 1 \u00d7 10 4 in one patient. The viral load became negative in the only patient who survived. In the four patients who did not survive, DNA", "Title: Egr-1 regulates RTA transcription through a cooperative involvement of transcriptional regulators\nPassage: The cells were harvested and processed for the detection of Egr-1 phosphorylation through immunoprecipitation and immunoblotting. d. 10 \u00d710 6 BCBL-1 cells were induced with TPA for 24h. The cells were harvested and processed for the detection of Egr-1 phosphorylation through immunoprecipitation and immunoblotting. Title: Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1", "Passage: Of particular interest, EGR1 directly controls proliferation when activated by the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in mitogen-stimulated astrocytes . Virus-induced changes in EGR1 expression have been observed in several in vitro systems. In HIV-1-infected astrocytes, EGR1 upregulation was found to be induced by Tat through transactivation of the EGR1 promoter, leading to cellular dysfunction and Tat-induced neurotoxicity . Increased amounts of EGR1 mRNA have also been demonstrated to act in a region-specific manner, corresponding temporally with viral RNA production in the brain tissues of rats infected with either rabies virus or Borna disease virus . Title: Egr-1 regulates RTA transcription through a cooperative involvement of transcriptional regulators", "Passage: Since the expression and phosphorylation of Egr-1 is one of the key factors in regulating viral reactivation , we wanted to determine whether Egr-1 gets phosphorylated during the initial burst of lytic cycle during de novo infection. To this end, we used a monocytic cells, THP-1 and endothelial cells, HUVECs for de novo infection as these cells represent a model for studying KSHV primary infection . The infection of HUVECs and THP-1 with KSHV showed augmented Egr-1 phosphorylation when compared with the respective mock infected cells . Next, we verified whether active infection was responsible for Egr-1 phosphorylation by infecting Title: Egr-1 regulates RTA transcription through a cooperative involvement of transcriptional regulators", "Passage: To study the direct effects of Egr-1 expression during KSHV infection, THP-1 and HUVECs cells were depleted of Egr-1 by transfecting specific siRNA for Egr-1 or scrambled siRNA as a control. The depletion of Egr-1 in the target cells was confirmed through amplification of Egr-1 specific transcripts by RT-PCR .", "Title: A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice\nPassage: more suspected, indicating spread to continental America is possible. CHIKV is transmitted to humans by Aedes aegypti and Aedes albopictus mosquitoes, the latter of which has been an important vector in many of the recent outbreaks due to mutations in the envelope genes of the virus that allow for more efficient transmission . Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: During the 7 d preceding birth, no human mother has been reported to transmit the disease vertically. However, about 50% of newborns delivered while the mother was infected with CHIKV contracted the disease from their mother, despite the method of delivery. Furthermore, there have been instances of CHIKV transmission from mother to fetus causing congenital illness and fetal death . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: There are always certain risks associated with live attenuated or inactivated viral vaccines . One way to avoid these potential problems is to construct a consensus-based DNA vaccine. DNA based vaccines have an improved safety profile as compared to live or attenuated vaccines . A consequence of CHIKV's rapid evolution is difficulty in constructing a vaccine that will be able to Figure 3 . Levels of CHIKV-specific IgG in mice immunized with CHIKV vaccines. Each group of C57BL/6 mice was immunized with 12.5 mg of pVax1 control vector or CHIKV vaccine plasmids as indicated at 0 and 2 wk. Mice Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: During the 2005-2006 La Reunion Island outbreaks, Ramful et al. discovered that mothers could transmit CHIKV to their progeny during the perinatal period , and it is associated with a high degree of morbidity. By mean Day 4 of life, all of the neonates were symptomatic for CHIKV, exhibiting common CHIKF symptoms. Six neonates were confirmed to have contracted CHIKV and developed mengoencephalitis. Of those mothers who, during the La Reunion Island epidemic, were infected long before delivery, only three fetal deaths were reported . Ramful et al. theorized that motherto-child transmission most likely happens transplacentally shortly before delivery .", "Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics\nPassage: The RSV treatment ribavirin is limited due to difficulty with aerosol delivery, cost and potential harm to healthcare workers, despite off-label treatment of immunocompromised patients being reasonably successful. In the immunocompromised, therapy with a concomitant immunoglobulin or palivizumab has had mixed results, probably due to the difficulty of knowing when to initiate treatment . Title: Pharmacotherapy of Lower Respiratory Tract Infections in Elderly\u2014Focused on Antibiotics", "Passage: Ribavirin is a nucleoside analogue with broad-spectrum antiviral activity by inhibiting viral RNA synthesis and mRNA capping . The efficacy of ribavirin alone or in combination with IFN-\u03b2 for the treatment of SARS is inconsistent and controversial , and Canada announced a ban on ribavirin for the treatment of SARS due to the reported side effects and inadequate efficacy . Lopinavir and ritonavir are protease inhibitors that may inhibit the 3C-like protease of MERS, they improve clinical outcome compared with ribavirin alone in SARS patients Stockman et al., 2006) . There are still no commercial vaccines available against MERS-CoV . Title: Characteristics of human infection with avian influenza viruses and development of new antiviral agents", "Passage: Ribavirin and arbidol have long been recognized as broadspectrum antiviral agents against viruses from different families. Viruses resistant to these treatments have rarely been observed . The target of ribavirin is a cellular enzyme, inosine 5'-monophosphate dehydrogenase, which is involved in viral RNA synthesis and cellular biosynthesis of GTP. The IC 50 of ribavirin on H5N1 ranged from 6 to 22 \u03bcmol/L in vitro . Ribavirin 75 mg\u00b7kg -1 \u00b7d -1 protected 70% of mice from lethal H5N1 infection . The clinical efficacy of ribavirin on influenza was less effective than that of adamantanes or NA inhibitors and more dependent Title: Possible therapeutic effect of orally administered ribavirin for respiratory syncytial virus-induced acute respiratory distress syndrome in an immunocompetent patient: a case report", "Passage: severe pneumonia in non-influenza respiratory viral infections in babies and children . However, there is concern about its use due to its high cost, teratogenicity, and potentially administered risk of lung function decline. In addition, intravenously administered or aerosolized ribavirin unfortunately is not readily available in our country because we can acquire this agent only through the Korea Orphan & Essential Drug Center , which may cause delay in the start of treatment. Meanwhile, orally administered ribavirin is relatively safe and economic, and several reports have suggested that it is associated with favorable clinical outcomes in RSV infection . Thus,", "Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study\nPassage: represented two different co-circulating lineages . Lineage I is A/Bayern/7/ 95-like and lineage II include the H1N1 strains of today and the A/New Caledonia/20/99 vaccine reference strain . The phylogenetic trees of NA and the internal genes showed the same topology . The lineage II strains are characterised by a deletion K130 in HA Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study\nPassage: We did not observe amino acids in the N2 NA protein that would decrease virus replication in eggs. The amino acids known to give good replication in eggs were all present in this dataset. Title: Genetic heterogeneity in the leader and P1-coding regions of foot-and-mouth disease virus serotypes A and O in Africa", "Passage: There was a difference in the groupings for the 1A trees when compared to the P1 and other capsid-coding gene regions where three non-African A isolates clustered with the non-African O viruses . The phylogenetic tree representing the region encoding the L protein differed from that of the structural proteins where sub-grouping according to serotype was much less apparent, which was consistent with previous findings for this region . Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study\nPassage: for overlapping regions giving a higher dN/dS ratio .", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: CDC Summary 21 MAR 2020,", "Passage: COVID-19 is caused by a coronavirus. Coronaviruses are a large family of viruses that are common in people and many different species of animals, including camels, cattle, cats, and bats. Rarely, animal coronaviruses can infect people and then spread between people such as with MERS-CoV, SARS-CoV, and now with this new virus . Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Text: Coronaviruses are spherical, enveloped, and the largest of positive-strand RNA viruses. They have a wide host range, including birds, farm animals, pets, camels, and bats, in which they primarily cause respiratory and gastrointestinal disease. Belonging to the order Nidovirales, family Coronaviridae, and the subfamily Orthocoronaviridae there are four genera of coronaviruses-Alphacoronavirus, Betacoronavirus, Deltacorona virus, and Gammacoronavirus . Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia", "Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus\nPassage: The host-virus interface is a fundamental aspect in defining the molecular pathogenesis of HIV-1 . Indeed, with its limited repertoire of viral proteins, HIV-1 relies extensively on the host cell machinery for its replication. Several recent studies have capitalized on the recent advances in the ''OMICS'' technologies, and have revealed important insights into this finely tuned molecular dialogue . HIV-1 Tat is essential for viral replication and orchestrates HIV-1 gene expression. The viral regulatory protein is known to interact with an extensive array of cellular proteins and to modulate cellular gene expression and signaling pathway . We and others have Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: of nucleolar proteins of our dataset with HIV-1 pathogenesis and HIV-1 Tat in particular. This further increases our confidence in our experimental strategy and suggests a role for Tat in the spatial control and subcellular compartimentaliation of these cellular cofactors. Ultimatly, our study provides new insights on the importance of Tat in the cross talk between nucleolar functions and viral pathogenesis. Importantly, we have also identified changes in nucleolar protein abundance that were not previously associated with HIV-1 pathogenesis, including proteins associated with metabolic pathways, which provide new potential targets and cellular pathways for therapeutic intervention. Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: Interestingly, using a different cellular system, a drosophila melanogaster Tat transgenic strain, Ponti et al, analysed the effects of Tat on ribosome biogenesis, following 3 days heat shock treatment to induce Tat expression under the control of the hsp70 promoter . Following Tat expression, they observed a defect in pre-rRNA processing associated with a decrease in the level of 80S ribosomes . Nevertheless, the different cellular system employed combined with the 3 days heatshock induction make their results difficult to compare with ours. Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: Jurkat T-cells are robust and present the advantage to grow without stimulations and are easely transduced using retroviral gene delivery. Importantly, they have been widely employed to evaluate Tat-mediated pathogenesis using system-wide approaches and to analyse T-cell key cellular signaling pathways and functions . Indeed, we have found them particularly suited for prolongued in vitro culture in SILAC medium and subsequent isolation of their nucleolus followed by MS analysis, which requires up to 85 millions of cells. We fused Tat to the TAP tag to enable future downstream applications such as Tandem affinity purification or Chromatin IP analysis. Importantly, we", "Title: Influenza virus-related critical illness: prevention, diagnosis, treatment\nPassage: Preferred respiratory specimens for influenza testing in hospitalized patients without lower respiratory tract disease include nasopharyngeal, mid-turbinate nasal, or combined nasal-throat swabs. Collection of lower respiratory tract specimens should be considered in hospitalized patients with suspected influenza if upper respiratory tract specimens are negative and a positive test would result in a change of clinical management , because viral replication in the lower respiratory tract may be ongoing and prolonged after virus is no longer detectable in the upper respiratory tract . Influenza Apdm09 virus in particular has been shown to have affinity for infecting the lower respiratory tract . Title: Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?", "Passage: Samples for microbiologic diagnosis were taken by endotracheal aspiration with a 14F sterile probe to a depth of 2 cm from the distal end of the endotracheal tube. The secretions obtained were collected in a sterile container and transported in sterile packages to the microbiology laboratory for Gram staining and bacterial and viral procedures. Title: Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?\nPassage: In 17 of the 31 patients, influenza testing was performed simultaneously in the TA and nasopharyngeal samples. The upper respiratory tract sample failed to detect influenza in 17.6% of cases. Title: Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?", "Passage: influenza is by detection of the virus in culture or RT-PCR with a nasopharyngeal aspirate/swab or lower respiratory tract sample . Because viral shedding peaks at 48 hours after the onset of illness and declines thereafter, testing of lower respiratory tract samples in patients with compromised lung parenchyma may be more beneficial . Accordingly, we found that the upper respiratory tract sample did not reveal influenza in 17.6% of cases. Diagnostic viral load tended to be higher in patients with suspected influenza, possibly as a result of the earlier diagnosis of influenza after onset of symptoms in this group compared", "Title: Polymicrobial intensive care unit-acquired pneumonia: prevalence, microbiology and outcome\nPassage: Drug resistance of pathogens was defined according to a recent report . MDR pathogens were defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Extensive drug resistance was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories . Pan drug resistance was defined as non-susceptibility to all agents in all antimicrobial categories. We considered methicillin-resistant Staphylococcus aureus , and Enterobacteriaceae producing extended-spectrum \u03b2-lactamase as MDR pathogens . Title: Multi-drug resistance of blood stream, urinary tract and surgical site nosocomial infections of Acinetobacter baumannii and Pseudomonas aeruginosa among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia: a cross-sectional study", "Passage: The non-fermentative gram negative bacilli A. baumannii and P. aeruginosa have emerged as serious particular concern . They are among the most common and serious MDR pathogens documented along with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Enterobacter spp., collectively acronyms and considered as ESKAPE pathogens and superbugs, respectively . Title: Multi-drug resistance of blood stream, urinary tract and surgical site nosocomial infections of Acinetobacter baumannii and Pseudomonas aeruginosa among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia: a cross-sectional study", "Passage: The hospital environment contains a large number of immuno-compromised individual's and patients with diverse bacterial pathogens and normal microbiota . NI accounted 7-10% prevalence in the world . According to 2014 World Health Organization report, 15% of all the hospitalized patients suffered from NIs . Title: Epidemiology of Multi-Drug Resistant Organisms in a Teaching Hospital in Oman: A One-Year Hospital-Based Study\nPassage: amikacin showing greatest efficacy. Another study carried out at a tertiary care hospital in Riyadh over a The Scientific World Journal 5 one-year period showed the most frequent pathogens to be P. aeruginosa, E. coli, S. aureus, K. pneumoniae, and S. marcescens.", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: One of the critical issues in infectious disease epidemiology is that the time of infection event is seldom directly observable. For this reason, the time of infection needs to be statistically estimated, employing a backcalculation method . Using a sophisticated statistical model with doubly intervalcensored likelihood and right truncation with an exponential growth of cases, the mean incubation period has been estimated to be about 5.0 days . To understand the time-dependent risk of infection throughout the course of outbreak and estimate the effectiveness of the quarantine measure from 5 to 19 February 2020, I aimed to estimate the incidence Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Abstract: To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus . The epidemic curve of a total of 199 confirmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Text: An outbreak of novel coronavirus disease has occurred on a cruise ship, the Diamond Princess . The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a", "Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy\nPassage: much higher concentration and longer circulation time . The pharmacokinetic profiles of AP3 and AP2 fit a non-compartment model. The pharmacokinetic parameters were calculated with PK Solver. The in vivo elimination half-life of AP3 was about 2.8-fold longer than that of T20 . This result provided the theoretical basis for reducing the injection frequency and dose of the fusion inhibitor, in conjugation with the improved antiviral potency of AP3. Therefore, replacement of T20 with AP3 may significantly reduce injection-site reactions and the drug cost, which would promote the clinical applications of the HIV fusion inhibitor in resource-poor regions or countries. Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: much higher concentration and longer circulation time . The pharmacokinetic profiles of AP3 and AP2 fit a non-compartment model. The pharmacokinetic parameters were calculated with PK Solver. The in vivo elimination half-life of AP3 was about 2.8-fold longer than that of T20 . This result provided the theoretical basis for reducing the injection frequency and dose of the fusion inhibitor, in conjugation with the improved antiviral potency of AP3. Therefore, replacement of T20 with AP3 may significantly reduce injection-site reactions and the drug cost, which would promote the clinical applications of the HIV fusion inhibitor in resource-poor regions or countries. Title: 3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors", "Passage: Twenty pharmacophore models were generated with default parameters after Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database run, and their statistical values are listed in Table 4 . Each of the obtained models represents a different tradeoff among the conflicting demands of maximizing steric consensus, maximizing pharmacophore consensus, and minimizing energy. All the twenty models had Pareto rank 0, which means no one model is superior to any other one. Model_03 has very high energy, which is recognized that a high-energy value is due to steric clashes . Small value of energy and high values of Specificity, N_hits, Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: AP3 had longer half-life than T20. Although T20 has shown efficacy in inhibiting HIV-1 infection, its major weakness lies in its short half-life in plasma . As a result, T20 has to be administered subcutaneously twice daily at 90 mg per dose, often causing serious injection-site reactions 25, 26 . Here, we performed pharmacokinetic studies by intravenous administration of AP3, AP2, and T20, respectively, to SD rat at a dose of 1 mg/kg, in order to compare their in vivo circulation time. As expected, T20 exhibited a shorter half-life and lower AUC from systemic circulation, while AP3 and AP2 demonstrated", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: and August 2013 may have been triggered by an index case becoming infected through DC contact . Sequencing MERS-CoV genomes from the 2013 Al-Ahsa hospital outbreak indicated that multiple viral variants contributed to the cases but that most were similar enough to each other to be consistent with human-tohuman transmission. Molecular epidemiology has revealed otherwise hidden links in transmission chains encompassing a period of up to five months . However, most outbreaks have not continued for longer than two to three months and so opportunities for the virus to adapt further to humans through co-infection and sustained serial passage have Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: There appears to be a 2-3 % prevalence of MERS-CoV in the KSA with a 5 % chance of secondary transmission within the household. There is an increased risk of infection through certain occupations at certain times and a much greater chance for spread to other humans during circumstances created by humans, which drives more effective transmission than any R 0 would predict on face value. Nonetheless, despite multiple mass gatherings that have afforded the virus many millions of opportunities to spread, there have remarkably been no reported outbreaks of MERS or MERS-CoV during or immediately after these events. There Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The first known MERS human-to-human transmission event was one characterized by acute LRT disease in a healthcare setting in Jordan. In stark contrast, a sero-survey of HCW who were sometimes in close and prolonged contact with the first, fatal MERS-CoV case in 2012 , found none of the HCW had seroconverted four months later, despite an absence of eye protection and variable compliance with required PPE standards .", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: DNA Vaccines\u2014How Far From Clinical Use?", "Passage: The delivery vector has to offer a sufficient capacity to efficiently package DNA/RNA per se, which is an obstacle especially for longer plasmid DNA , in order to enable delivery of a sufficient amount of molecules per target cell . The delivery system has to show stability against serum proteins that may form a protein corona around the NC and thereby affect its targeting and uptake efficiency . After uptake by the cell, the NC cargo has to evade endo/lysosomal degradation and to enter the cytoplasm by endosomal escape . While released mRNA is translated directly in the cytoplasm, Title: Recombinant vector vaccine evolution", "Passage: Evolution is not the only consideration in designing a recombinant vector vaccine, and the model helps us identify vaccine properties that promote efficacy. First the vaccine should elicit an immune response that rapidly clears the pathogen . Second, the vaccine should elicit a large response to this antigen. This requires that the antigen rapidly elicits immunity , and also requires a high vaccine viral load to generate a large response. Engineering this requires tackling a trade-off between avoiding vaccine clearance but allowing for rapid clearance of the pathogen . Vaccines designed to express the antigen in a form that is Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: comparison of the properties of several strains that are commonly used as DNA vaccine carriers is presented in Table 1 . , and inside the DCs, the antigen gene is expressed as protein, which will later be presented by class I or II MHC and delivered to CD4+ or CD8+ T cells.", "Title: Estimating the number of infections and the impact of non-\nPassage: earlier stages of their epidemic with fewer deaths . Title: Estimation in emerging epidemics: biases and remedies\nPassage: Using the 1000 simulated epidemic trajectories, the estimators a) -e) of the exponential growth rate r and their usefulness in predicting the epidemic size 6 weeks after reaching 4500 notified cases were tested. The methods a) -d) estimate r using data from the last 6 weeks before reaching level 4500, while the fifth method, based on the discretized renewal equation , Section 2 of main paper) estimates R 0 , using regression weights derived from the estimated generation time distribution based on observed backward serial intervals, as suggested in . Title: Estimation in emerging epidemics: biases and remedies", "Passage: Duration of simulations Only \"exploding\" trajectories, corresponding to \"big\" outbreaks, are kept. Outbreaks start with 1 infected individual and are rejected if they do not reach 4500 reported cases. At the time of reaching this level, some statistics are collected and then the simulation is continued for 6 weeks further. The purpose of this continuation is that a prediction of the final level 6 weeks later is attempted, based on the first 4500 cases. Statistics are based on 1000 accepted trajectories. Title: Estimating the number of infections and the impact of non-\nPassage: intervention impact in many countries at earlier stages of their epidemic .", "Title: The Role of Phlebovirus Glycoproteins in Viral Entry, Assembly and Release\nPassage: Gn and Gc have a cysteine content of approximately 5% . Positions of the cysteine residues are highly conserved among phleboviruses , indicating that extensive disulfide-bridge formation may occur and that the positions might be crucial for determining correct polypeptide folding. For Gn and Gc of UUKV it could be demonstrated that both proteins interact with protein disulfide isomerase , an enzyme ubiquitously found in the ER which breaks up incorrectly formed disulfide bonds and catalyzes the formation of the correct ones leading to the mature, correctly folded three-dimensional protein structure. Other proteins involved in correct folding of UUKV Gn Title: The Role of Phlebovirus Glycoproteins in Viral Entry, Assembly and Release", "Passage: two ER chaperones, are required for appropriate folding of Gn and Gc. Similarly, protein-disulfide-isomerase catalyzes Gn and Gc folding by promoting the formation of disulfide bonds, while calreticulin prevents misfolded Gn and Gc from being exported from the ER to the Golgi; Correctly folded Gn/Gc heterodimers are transported into the Golgi apparatus where they associate with RNPs via the cytoplasmic tails of Gn during the budding process; After budding of new virus particles into the Golgi is complete, virus-containing vesicles are transported to the plasma membrane where the virions are released by exocytosis. DC: dendritic cell; M\u03c6: macrophage; CME: clathrin-mediated Title: The Role of Phlebovirus Glycoproteins in Viral Entry, Assembly and Release", "Passage: Gn and Gc form non-covalently linked heterodimers in the ER . The two glycoprotein molecules which associate as a heterodimer do not necessarily originate from the same precursor protein. In the case of UUKV, Gn matures significantly faster than Gc . Therefore, newly synthesized Gn can only dimerize with Gc, which was synthesized earlier . In contrast, in the case of PTV, heterodimers are formed by Gn and Gc molecules synthesized at the same time suggesting that PTV and RVFV Gn and Gc maturate with similar kinetics . Title: Co-expression of RNA\u2013protein complexes in Escherichia coli and applications to RNA biology", "Passage: into the pBSTNAV vector, whereas the gp10 protein that selectively binds to it was cloned into the pACYCT2 vector. As shown in Figure 1 , good levels of expression of both pRNA and gp10 were obtained 3 h after addition of 1 mM IPTG in exponential phase of cell growth. The remaining two examples deal with the co-expression of the MS2 coat protein with, respectively, the AtRNA-mala, a tRNA-RNA fusion of 127 nt, and the AtmRNA . High levels of expressions of both RNA and protein were observed. Therefore, these three examples validate the feasibility of co-expressing RNA and protein", "Title: Immunity-Related Protein Expression and Pathological Lung Damage in Mice Poststimulation with Ambient Particulate Matter from Live Bird Markets\nPassage: Male BALB/c mice were purchased from Shandong University Laboratory Animal Center. All animal experiments were conducted in a Biosecurity Level 2+ laboratory, with mice kept on a 12-h light-dark cycle in controlled temperature and humidity . Animals were allowed free access to tap water and regular rodent food. Mice that were 6 weeks old and weighing about 13 g at the beginning of the experiments were used. All animals were sacrificed by lethal sodium pentobarbital injection. Title: Immunity-Related Protein Expression and Pathological Lung Damage in Mice Poststimulation with Ambient Particulate Matter from Live Bird Markets", "Passage: No significant differences emerged in the four PM-treated groups compared with the control group . Title: Immunity-Related Protein Expression and Pathological Lung Damage in Mice Poststimulation with Ambient Particulate Matter from Live Bird Markets\nPassage: The body weight of mice repeatedly exposed to the four kinds of PM was consistently lower than that of the control group. The average weight of four groups of PM-treated mice in Week 4 of exposure was 17.0 \u00b1 0.5 g, which was significantly lower than that of mice in the control group . There were no significant differences among the four groups of PM-treated mice . Title: Lung tissue bioenergetics and caspase activity in rodents", "Passage: Wistar rats and C57Bl/6 mice and BALB/c mice used in this study were maintained at the animal facility that was in compliance with NIH guidelines . All animals were housed in rooms maintained at 22\u00b0C with~60% relative humidity and a 12-hr light/dark cycle. They had ad libitum access to standard rodent chow and filtered water. The study was approved by the Animal Research Ethics Committee for care and use of laboratory animals at the College of Medicine and Health Sciences, UAE University.", "Title: Existing health inequalities in India: informing preparedness planning for an influenza pandemic\nPassage: Policies for those at greater risk of exposure and unable to social distance During a pandemic, non-pharmaceutical interventions include community or home quarantine, closing schools, prohibition of public gatherings, as well as behaviour change messages regarding washing hands often and covering your cough and sneeze. Yet the unequal capabilities of different communities to adhere to such measures are not acknowledged. For example, the pandemic plan of India fails to acknowledge the potential inefficacy of closing schools in reducing the spread of disease among the urban poor living in crowded environments. Similarly, whereas public markets may need to be closed to Title: Pandemic influenza preparedness: an ethical framework to guide decision-making", "Passage: Let us take the issue of targeting and prioritizing populations for vaccine and antivirals to illustrate how the values in the ethical framework can help guide decision-making. The values of solidarity and protecting the public from harm would require that priorities be set to maximize the capacity to help society ensure that the ill are cared for during a pandemic. Furthermore proportionality would require that decision-makers consider who within the community are most vulnerable to the contagion as well as who are most likely to benefit from immunization. A well-informed public conversant with the values in the ethical framework and Title: Pandemic Influenza Planning in the United States from a Health Disparities Perspective", "Passage: be minimized through careful planning that considers and proactively addresses vulnerability at each level: exposure to disease, susceptibility to disease if exposed, and treatment of disease. Public offi cials should systematically consider the additional barriers faced by socially disadvantaged groups at each of these levels and then actively seek ways to address those barriers. Local service providers, leaders of community-based organizations and other organizations working with socially vulnerable groups, and leaders of labor unions representing low-wage service workers are likely to have valuable insights and should be included in the planning process. Plans calling for stakeholder involvement without explicitly emphasizing Title: Pandemic Influenza Planning in the United States from a Health Disparities Perspective", "Passage: On a US government website for pandemic infl uenza , a question asks which groups would be especially vulnerable during an infl uenza pandemic. The answer notes that people may be vulnerable for a variety of reasons, including limited access to healthcare; limited profi ciency in English; or being disabled, homeless, economically disadvantaged, or a single parent. The response calls for faith-based and community-based organizations to develop plans \"to care for dependent populations\" and to \"provide fi nancial aid to the poor who are unable to work and are in need of emergency income for housing, medicine, or other essential", "Title: Asthma in the elderly: what we know and what we have yet to know\nPassage: distinguish one from another . The major distinguishing clinical features between the two diseases are personal or family history of atopy and/or asthma with symptoms starting in childhood being more likely with asthma; cigarette smoking history and adult onset of symptoms being more likely in COPD; and increased biomarkers including fractional exhaled nitric oxide, peripheral and sputum eosinophil and serum total and specific IgE being more likely with asthma . However, exceptions are not unusual, and the LOA phenotype may not exhibit many of the distinguishing factors for asthma . Title: Asthma in the elderly: what we know and what we have yet to know", "Passage: The symptoms of asthma and COPD are very similar, if not identical. The major differences are the degree of reversibility is often greater in asthma and the persistence of dyspnea is greater in COPD. Both are characterized by exacerbations which respond to corticosteroids and bronchodilators, infections triggering exacerbations, episodic wheezing, cough with or without mucous production, improvement with chronic inhaled corticosteroids and bronchodilators, and decreased exercise tolerance. The chronic bronchitis phenotype of COPD as opposed to the emphysematous phenotype is more likely to be confused with asthma, but the variations of phenotypes in both diseases confounds simple measures to reliably Title: The Importance of Bacterial and Viral Infections Associated with Adult Asthma Exacerbations in Clinical Practice", "Passage: Eligible patients were aged over 18 years and had a clinical diagnosis of asthma supported by one or more other characteristics: variability in peak expiratory flow of more than 20%; airway reversibility by inhaled \u03b22 agonist; hyperresponsiveness to methacholine challenge; and recurrent dyspnea episodes with wheezing. Title: Asthma in the elderly: what we know and what we have yet to know", "Passage: Whereas younger patients with asthma often suffer from allergic rhinitis complaints, elderly patients with asthma often suffer from sinus symptoms, including nasal obstruction, loss of smell and facial pain/headache. A recent Europe-wide epidemiologic study on the prevalence of chronic rhinosinusitis did confirm the well-known association between allergic rhinitis and early-onset asthma, but also demonstrated a clear increased risk to suffer from late-onset asthma in CRS patients . CRS may be phenotyped as CRS without and with nasal polyps , based on symptoms , nasal endoscopy and CT scanning. From those phenotypes, CRSwNP has a clearly increased risk of asthma comorbidity", "Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking\nPassage: With the ability to directly bind to DNA and regulate the expression of adjacent genes, nuclear receptors are a class of ligand-inducible transcription factors. They regulate various biological processes, such as homeostasis, differentiation, embryonic development, and organ physiology . The NR superfamily has been classified into seven families: NR0 ; NR1 , NR2 , NR3 , NR4 , NR5 , and NR6 . Since they are involved in almost all aspects of human physiology and are implicated in many major diseases such as cancer, diabetes and osteoporosis, nuclear receptors have become major drug targets , along with G protein-coupled receptors Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking", "Passage: Text: With the ability to directly bind to DNA and regulate the expression of adjacent genes, nuclear receptors are a class of ligand-inducible transcription factors. They regulate various biological processes, such as homeostasis, differentiation, embryonic development, and organ physiology . The NR superfamily has been classified into seven families: NR0 ; NR1 , NR2 , NR3 , NR4 , NR5 , and NR6 . Since they are involved in almost all aspects of human physiology and are implicated in many major diseases such as cancer, diabetes and osteoporosis, nuclear receptors have become major drug targets , along with G protein-coupled Title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking", "Passage: Abstract: Nuclear receptors are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called \u201ciNR-Drug\u201d was developed. In the predictor, the drug compound concerned was formulated by a 256-D vector derived from its molecular fingerprint, and the NR by a Title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features", "Passage: Nuclear receptors are ligand-activated transcription factors that regulate the activation of a variety of important target genes, which are the most important drug targets in terms of potential therapeutic application. According to our results, secondary structure and polarizability play the major role in determining the drug-NRs interactions. The conservative motif of the NR is typically described as three stacked alpha-helical sheets. The helices that make up the ''front'' and ''back'' sheets are aligned parallel to one another. The helices in the middle sheet run across the two outer sheets and only occupy the space in the upper portion of the", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: Many interferons from the three classes have been tested for their antiviral activities against SARS-CoV both in vitro and in animal models. Interferon \u03b2 has consistently been shown to be the most active, followed by interferon \u03b1. The use of corticosteroids with interferon alfacon-1 appeared to have improved oxygenation and faster resolution of chest radiograph abnormalities in observational studies with untreated controls. Interferon has been used in multiple observational studies to treat SARS-CoV and MERS-CoV patients . Interferons, with or without ribavirin, and lopinavir/ritonavir are most likely to be beneficial and are being trialed in China for 2019-nCoV. This drug Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: The modulation of SARS-CoV pathogenesis, for example, was reported to be independent of all three types of interferon signaling mechanisms, with SARS-CoV ORF 3b, ORF 6, and nucleocapsid proteins identified to interfere with interferon signaling through various mechanisms . However, STAT1 has been shown by the same group to be crucial in activating innate immune signaling pathways during SARS-CoV infection, with a secondary role in the prevention of uncontrolled cell reproduction . In contrast, PRRSV appears to be receptive to both IFN-\u03b1 and -\u03b2 dose-dependent treatment ; however, pigs infected with PRRSV do not evoke significant IFN responses, with little Title: Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review", "Passage: IFNs are signaling proteins that are produced and secreted by host cells in response to pathogens or tumor cells. They are currently approved for the treatment of hepatitis C 64 as well as certain autoimmune disorders like multiple sclerosis. 65 During recent viral outbreaks, IFNs have been suggested as a potential treatment for emerging viral infections, such as the severe acute respiratory syndrome coronavirus. 66 The antiviral activity of IFNs appears to occur via the induction of IFNs-induced transmembrane proteins, which inhibit a broad range of viruses at different stages of the virus life cycle, including viral entry and fusion. Title: Influenza A Virus Inhibits Type I IFN Signaling via NF-\u03baB-Dependent Induction of SOCS-3 Expression", "Passage: The phosphorylated transcription factors dimerise and bind to IRF-9 . The newly formed heterotrimer, called IFNstimulated gene factor 3 , translocates into the nucleus and binds to IFN-stimulated response elements , to initiate gene transcription of ISGs. Treatment of cells with type I IFN upregulates expression of an array of genes including SP110, IRF-1 and many others . Among these ISGs the 29, 59oligoadenylate synthetase 1 , the Mx proteins and the dsRNA-activated protein kinase are described to directly interfere with viral replication . Both, PKR and the OAS1/ RNaseL system are capable of inhibiting cellular and viral translation.", "Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically: Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: Significance and potential impact of the study To provide greater insight into social network structures in resource poor settings, we propose to study social contact patterns within schools and households and compare and contrast patterns in the urban and rural setting exhibiting different demographic, economic, and socio-cultural characteristics. This will provide key data for use in transmission dynamic models for common respiratory viral and bacterial infections such as RSV and S. pneumoniae that are the leading cause of childhood morbidity and mortality in the SSA setting. We also seek to answer the question how we can optimize study design to", "Title: A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice\nPassage: adjuvants and normally elicit weak T cell responses. In contrast, MVA has been shown to be safe in thousands of human patients micro-neutralization assay and ELISA , respectively. Prime only MVA-GFP data is not shown because it does not differ with the prime & boost groups. Mice were monitored for 14 days following challenge for survival and footpad swelling . The first three days following challenge viremia levels were measured via TCID 50 . The dotted line indicates the limit of detection of the assay. doi:10.1371/journal.pntd.0002970.g002 Title: Viral vector-based influenza vaccines", "Passage: in the absence of any serious adverse events. 23 However, the use of MVA as a vaccine vector has multiple alternative advantages. Notably, MVA safety was confirmed in various in vivo models, including avian species and mammals with immunodeficiencies, leading to classification of MVA as a biosafety level 1 pathogen. Additional advantages of MVA as a vaccine vector include: easy insertion of antigens of interest into the viral genome, transient expression of heterologous antigens in vivo and induction of both humoral and cellular responses in animal models and humans. Finally, an interesting characteristic of MVA is that compared to VV, Title: Virus-Vectored Influenza Virus Vaccines", "Passage: magnitude of the antigen-specific effector functions . MVA is also a potent activator of early innate immune responses further enhancing adaptive immune responses . Between early smallpox vaccine development and more recent vaccine vector development, MVA has undergone extensive safety testing and shown to be attenuated in severely immunocompromised animals and safe for use in children, adults, elderly, and immunocompromised persons. With extensive pre-clinical data, recombinant MVA vaccines expressing influenza antigens have been tested in clinical trials and been shown to be safe and immunogenic in humans . These results combined with data from other clinical and pre-clinical studies support Title: Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines", "Passage: have a better safety profile than replication-competent vaccinia virus, a relatively large inoculum volume of 0.05 to 0.10mL and 0.5 to 1mL of MVA or recombinant MVA is typically used in small animal models and in non-human primates/humans, respectively. This often results in local reactions at the site of inoculation, including muscle ache, pain, and tenderness . In addition, the inoculation of prophylactic or therapeutic regimens with needles and syringes can be problematic for some people, a global problem commonly called needle phobia or fear of the needle in common phraseology. Although the use of needle-free injection devices such as", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Childhood pneumonia can also lead to significant morbidity and chronic disease. Early life pneumonia can impair longterm lung health by decreasing lung function . Severe or recurrent pneumonia can have a worse effect on lung function; increasing evidence suggests that chronic obstructive pulmonary disease might be related to early childhood pneumonia . A meta-analysis of the risk of long-term outcomes after childhood pneumonia categorized chronic respiratory sequelae into major and minor groups . The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Childhood pneumonia and clinically severe disease result from a complex interaction of host and environmental risk factors . Because of the effectiveness of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination for prevention of radiologic and clinical pneumonia, incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Improved access to health care, better nutrition and improved living conditions might contribute to further decreases in childhood pneumonia burden. The WHO Integrated Global Action Plan for diarrhea and pneumonia highlights many opportunities to protect, prevent and treat children . Breastfeeding rates can be improved by programs that combine education and counseling interventions in homes, communities and health facilities, and by promotion of baby-friendly hospitals . Improved home ventilation, cleaner cooking fuels and reduction in exposure to cigarette smoke are essential interventions to reduce the incidence and severity of pneumonia . Prevention of pediatric HIV is possible by providing interventions Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: odds of severe pneumonia by 2.7 times in low-and middle-income countries and 1.3 times in highincome countries. Markers of undernutrition are strong risk factors for pneumonia in low-and middle-income countries only, with highly significant odds ratios for underweight for age , stunting and wasting . Household crowding has uniform risk, with odds ratios between 1.9 and 2.3 in both low-and middle-income countries and high-income countries. Indoor air pollution from use of solid or biomass fuels increases odds of pneumonia by 1.6 times; lack of measles vaccination by the end of the first year of age increases odds of pneumonia by", "Title: Proper Distance Metrics for Phylogenetic Analysis Using Complete Genomes without Sequence Alignment\nPassage: A distance matrix for all the genomes under study is then generated for the construction of phylogenetic trees. This distance method to construct phylogenetic tree is referred to as the dynamical language model method . Finally, we construct all trees using the neighbour-joining method in the software SplitsTree4 V4.10 or in the Molecular Evolutionary Genetics Analysis software based on the distance matrices. Title: Proper Distance Metrics for Phylogenetic Analysis Using Complete Genomes without Sequence Alignment", "Passage: . These two methods were also used to analyze the complete chloroplast genomes . The SVD method was used to analyze mitochondrial genomes of 64 selected vertebrates . A correlation-distance method without removing the random background ) was used to analyze rRNA gene sequences as DNA barcodes . Title: Calculation of Evolutionary Correlation between Individual Genes and Full-Length Genome: A Method Useful for Choosing Phylogenetic Markers for Molecular Epidemiology", "Passage: In order to estimate the evolutionary relationship between two nucleotide sequences, we introduced the r-value for calculation using pairwise distance matrices. As the basic data for certain algorithms to construct the trees, the pairwise distances determine the tree topology . Therefore, the correlation coefficient between two distance matrices can be used to estimate the similarity of two trees . Here, we firstly used this statistical method to estimate the evolutionary correlation levels between genome sequences and individual gene sequences so as to choose the proper consensus region for inferring the exact genetic relationship between viral isolates. The calculation was performed Title: Proper Distance Metrics for Phylogenetic Analysis Using Complete Genomes without Sequence Alignment", "Passage: shown in Figure 4 , our distance-based analysis shows that the mitochondrial genomes are separated into three major clusters. One group corresponds to mammals; one group corresponds to the fish; and the third one represents Archosauria . The interrelationships among the mitochondrial genomes are roughly in agreement with the current understanding of the phylogeny of vertebrates revealed by the traditional approaches. For further biological discussion, one can refer to .", "Title: Estimating the number of infections and the impact of non-\nPassage: study have implemented all major non-pharmaceutical interventions. Title: Estimating the number of infections and the impact of non-\nPassage: interventions became effective. Title: Estimating the number of infections and the impact of non-\nPassage: interventions. Title: Estimating the number of infections and the impact of non-\nPassage: We estimate that major non-pharmaceutical interventions have had a substantial impact on the time-", "Title: Human adenovirus type 7 infection causes a more severe disease than type 3\nPassage: Laboratory findings for the HAdV-7-positive inpatients were also significantly different from those infected by HAdV-3 . Specifically, the HAdV-7-positive inpatients had lower white blood cell count , platelet count . In contrast, hemoglobin and C-reactive protein levels, and the percentages of lymphocytes, neutrophils and positive sputum culture were found to be statistically similar. Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: Although our results implicate a novel type-specific relationship between adenoviral infection, it has potential limitations. The data presented herein only interrogated virological differences; however, adenovirus infection is a very complex process that involves not only the structural proteins of the virus, such as fiber, hexon, and penton, but also includes host and environmental factors. Nonetheless, our data confirm that severe adenovirus infection was associated with HAdV-7 rather than HAdV-3. The significance of the study lies in that the pediatrician should be aware of the importance of early diagnosis and treatment of HAdV-7 infection in children in clinical practice. The findings Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: Previous studies by Johnson et al. and others have shown that the complement is strongly activated by a wide range of negative-strand RNA viruses, including parainfluenza virus 5 , Nipah virus , mumps virus ; c-e The number of total cells and the differential counting of cells in BALF. f-i Concentration of cytokine IL-1\u03b2, TNF-\u03b1, and IL-6 in BALF; n = 4; *,**,*** indicate P < 0.05, 0.01, and 0.001, respectively, compared with the mock group; #, ##, ### indicate P < 0.05, 0.01, and 0.001, respectively, compared with HAdV-3 group implicate the plasma level of C3a as a marker Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: The severity of adenoviral infection, as studied in Chongqing, China, may be correlated to human adenovirus type 7 instead of type 3 . Overall, strain of the HAdV-7 type caused a more severe pneumonia and an exacerbated cytokine response, which also paralleled their more robust replication in cell culture, as compared to HAdV-3. While the exact mechanism of the type-specific pathogenicity merits further investigation, these findings may eventually contribute to better control and treatment of adenoviral infection.", "Title: Note from the editors: novel coronavirus (2019-nCoV)\nPassage: Text: The situation has continued to evolve rapidly since then and just a few weeks later, as at 23 January, 614 laboratory-confirmed cases and 17 deaths have been reported including some cases detected outside mainland China . Meanwhile, on 7 January 2020, the novel coronavirus, currently named 2019-nCoV, was officially announced as the causative agent by Chinese authorities . In order to support public health action, viral genome sequences were released by Chinese researchers on 10 January and 2 days later, four further sequences were also made available on the Global Initiative on Sharing All Influenza Data . While more Title: Note from the editors: novel coronavirus (2019-nCoV)\nPassage: Date: 2020-01-23 Title: Note from the editors: novel coronavirus (2019-nCoV)\nPassage: DOI: 10.2807/1560-7917.es.2020.25.3.2001231 Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the", "Title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy\nPassage: We identified filamentous EBOV particles 20 microns or longer, with a well ordered internal structure, and a helical nucleocapsid giving an internal ''herring-bone'' appearance using cryo-EM and cryo-ET . The nucleocapsid, as observed within intact viral particles, has a uniform helical structure and is enveloped by a membrane coated by an external layer of GP spikes. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes to a resolution of 14 \u00c5 as measured by the Fourier Shell Correlation 0.5 criterion. Virions are rarely straight. Title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 \u00c5 resolution", "Passage: Data and materials availability. The 3-D electron microscopy structure of the GP spike has been deposited into the Electron Microscopy Data Bank, www.emdatabank.org . Title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 \u00c5 resolution\nPassage: and symmetrical relationships between GP and the matrix protein VP40 in the envelope, and the underlying nucleocapsid layer . Title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 \u00c5 resolution", "Passage: base of the stalk in Fig. 2a , the three heptad repeat helices at the base of GP2 fit neatly into three strands visible in our EM 3-D structure, that appear to penetrate the virion membrane . Also, when viewed from the top, each blade has a smaller nub closer to the 3-fold axis that protrudes distally . Using the 332 kDa contour level, these nubs correspond closely with the receptor binding site, covering most of the residues known to be involved in binding, as well as protruding adjacent to the glycan cap regions. Each propeller blade, which is known", "Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: The Trojan Chicken Study, Minnesota\nPassage: The study design was further limited in that we did not account for time after exposure when photographs were taken. Since participants could drop by any time of the day, the time after exposure and duration of exposure likely varied between participants. In both the feasibility and pilot studies, the return rate was low, and tracking down participants was difficult. If similar studies are conducted in the future, a reward system might be used to increase compliance. Title: Gain-of-Function Research: Ethical Analysis\nPassage: at issue.", "Title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications\nPassage: changes to serve as potential reference markers of the innate responses of influenza infection. Given that RNAseq functions by reading virtually all the RNAs present in the samples tested, we can also discern the magnitude of each RNA change and mark them as the canonical responses. In addition, as RNAseq is not constrained by probe usage as in microarrays, they are therefore more reliable in detecting novel interactions during influenza infections of hNECs. Hence, RNAseq analysis will further augment the transcriptomic data established previously by microarray analysis. The augmented baseline can then be applied to future clinical studies and practice Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: studies in natural exacerbations and in viral-challenge models using RNA-sequencing or single cell RNA-seq on a range of time-points may provide important information regarding viral pathogenesis and changes induced within the airway of chronic airway inflammatory disease patients to identify novel targets and pathway for improved management of the disease. Subsequent analysis of functions may use epithelial cell models such as the air-liquid interface, in vitro airway epithelial model that has been adapted to studying viral infection and the changes it induced in the airway . Animal-based diseased models have also been developed to identify systemic mechanisms of acute exacerbation Title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications", "Passage: was generally higher than that of the microarray . In addition, RNAseq was also able to detect novel genes with expression changes of high magnitude that were generally higher than those found by microarray only . Genes such as HEATR9, PDCD1, IL4I1, ART3, and KCNH7 were altered to a higher magnitude than the 2.5-fold threshold. Hence, RNAseq-based transcriptomic analysis may augment transcriptomic findings to identify novel gene responses against influenza in the future. Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Alnylam pioneered the use of RNA interference which is a natural mechanism that regulates protein expression and is mediated by small interfering RNAs . Working with both groups, we manufactured an RSV Type A virus to GMP standard and titrated it in 35 human volunteers who we divided into five groups, each which was intranasally inoculated with increasing titre of the challenge virus. Intranasally. Overall, in this new model, 77% of volunteers consistently shed virus. Infection rate, viral loads, disease severity, and safety were similar between cohorts and were unrelated to the quantity of RSV received.", "Title: A High-Throughput Screening Approach To Repurpose FDA-Approved Drugs for Bactericidal Applications against Staphylococcus aureus Small-Colony Variants\nPassage: inhibits the \u2424-subunit of the bacterial RNA polymerase . Ketoconazole had the highest MIC, which is consistent with its inhibition of sterol synthesis, and is most effective in antifungal therapies. However, in regard to S. aureus, imidazole antifungals induce intracellular reactive oxygen species production . Yet, despite the different modes of action, no synergy between any of the 4 identified drugs was observed by fractional inhibitory concentration . Title: Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus", "Passage: and ofloxacin were 32 mg/L, 32 mg/L, 64 mg/L, 128 mg/L, and 4 mg/L, respectively, and these solutions were then serially diluted 2-fold with the same media. After a 24 h incubation at 37\u00b0C, the MICs were determined as described above. The fractional inhibitory concentration was calculated with a method previously described . FIC indexes of 0.5, >0.5 -4.0 and >4.0 were defined as synergy, no interaction and antagonism, respectively. Title: A High-Throughput Screening Approach To Repurpose FDA-Approved Drugs for Bactericidal Applications against Staphylococcus aureus Small-Colony Variants", "Passage: and plating serial dilutions on TSB agar. Scanning electron microscopy was also implemented to qualitatively assess the growth of the biofilm at 24 and 48 h. Growth control pegs were broken off, fixed in 2.5% glutaraldehyde/4% paraformaldehyde in 0.1 M cacodylate buffer, postfixed in 1% osmium tetroxide, dehydrated, and gold sputter coated prior to imaging. Gentamicin was compared against each of the validated hits at each tested concentration in a two-way ANOVA with Sidak's test for multiple comparisons. Differences were considered significant for P \u03fd 0.05. Testing was performed in triplicate. Title: Phenol-Rich Compounds Sweet Gel: A Statistically More Effective Antibiotic than Cloxacillin Against Pseudomonas Aeruginosa", "Passage: diameters of the inhibition zones were calculated. The standard anti-bacterial agent was cloxacillin. Data were evaluated using the IBM SPSS software program . The herbal extract groups and the control groups were compared at the 95% confidence interval, and the results were expressed as means \u00b1 standard deviations. Differences between the control group and the herbal extract groups were the criteria for the anti-bacterial activities. The t-test was used to detect differences between the treatment groups and the control group. A value of P < 0.05 was considered significant.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV was found and characterized because of its apparent association with severe, and therefore more obvious, illness in humans; we were the canaries in the coal mine. Sero-assays and prospective cohort studies have yet to determine the extent to which milder or asymptomatic cases contribute to MERS-CoV transmission chains. However, transmission of MERS-CoV is defined as sporadic , intra-familial, often healthcare associated, inefficient and requiring close and prolonged contact In a household study, 14 of 280 contacts of 26 MERS-CoV positive index patients were RNA or antibody positive; the rate of general transmission, even in outbreaks is around 3 % Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: of \"contact\" during these interviews has been defined for one study . Despite this lack of clarity, the WHO consider that evidence linking MERS-CoV transmission between DCs to humans is irrefutable . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first WHO case definition defined probable cases of MERS based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract involvement. It also included roles for contact with a probable or confirmed case or for travel or residence within the Arabian Peninsula. If strictly adhered to, only the severe syndrome would be subject to laboratory testing, which was the paradigm early on . From July 2013, the revised WHO case definition included the importance of seeking out and understanding the role of asymptomatic cases and from June 2014, the WHO definition more Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and", "Title: Nucleolus: the fascinating nuclear body\nPassage: participate in the early stages of rRNA processing, localize in the DFC, such as Wbrillarin and nucleolin along with the U3 snoRNAs , whereas proteins B23/NPM . The nucleolus is the gray structure surrounded by highly contrasted chromatin . Some chromatin Wlaments are also visible inside of the nucleolus . c, d Nucleolus of rat neurones in the day , and during the night which is the active period for the nucleolus of the rat. In the nonactive period , the nucleolus is reticulated with small FCs . In the active period, one giant FC is visible . Bar in Title: Nucleolus: the fascinating nuclear body", "Passage: region of chromosome 6 in Zea mays, this was the Wrst time the nucleolus was related to gene activity. In the 1950's the presence of RNAs in the nucleolus was demonstrated, and in the 1960's in situ hybridization techniques made it possible to identify ribosomal genes in the nucleolar organizer region . During the same period, mass isolation of nucleoli became possible leading to the biochemical characterization of nucleolar components. Based on these results it was proposed that ribosome biogenesis occurs in nucleoli. Given that the nucleolus became a subject of great interest, the \"International symposium on the nucleolus-its structure Title: Nucleolus: the fascinating nuclear body\nPassage: the cytoplasm. Title: Nucleolus: the fascinating nuclear body", "Passage: the cytoplasm. Title: Nucleolus: the fascinating nuclear body\nPassage: The nucleolus is the ribosome factory of the cell. In the nucleolus rDNAs are transcribed, the 47S precursor ribosomal RNAs are cleaved, processed and assembled with the 80 ribosomal proteins and the 5S RNA to form the 40S and 60S ribosomal subunits . This complex series of maturation and processing events, presently better characterized in yeast than in higher eukaryotes is under the control of about 150 small nucleolar RNAs and 2 large RNP complexes: the small subunit processome containing the U3 snoR-NAs and 40 proteins or Utps required for the 40S ribosomal subunit, and the large subunit processome required", "Title: Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome\nPassage: Of the HFRS-related complications, the frequencies of cardiac failure, ARDS and encephalopathy in the non-survivors were higher than those in the survivors , while the frequency of ARF in the survivors was higher than that of the non-survivors . There were no significant differences with respect to the frequencies of pneumonia, arrhythmia, gastrointestinal hemorrhage, hyperglycemia, concurrent bacteremia or secondary hypertension . Title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing", "Passage: dysfunction , hypervolemia, and blood electrolyte imbalance. The diuretic and convalescent phases are recovery stages that last for several weeks to months, and is characterized by progressive improvements in glomerular filtration rate, renal blood flow, and urine output control. A critical hallmark of HFRS is capillary leakage that results in edema and hemorrhage, suggesting that the vascular endothelium is damaged by cytokine storm against HTNV infection 19 . Hantavirus infections remain less understandable due to the lack of animal experimental models, difficulties in propagating the agent, and reverse genetic tools. Title: Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome", "Passage: The medical charts of 356 typical HFRS patients who were treated in the Center for Infectious Diseases, Tangdu Hospital, between January 2008 and August 2012 were selected randomly and reviewed. The diagnosis of HFRS was made based upon the detection of specific IgM and IgG antibodies to HTNV in acute phase serum specimens by enzyme-linked immunosorbent assay . Title: Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome", "Passage: In this study, the survivors tended to have prolonged hospital stays , which were consistent with the clinical course of HFRS. Generally, the hypotensive phase of HFRS usually occurs between day 3 and day 7 of the clinical course, and some critical patients even exhibit overlapping hypotensive and oliguric phases combined with various fatal complications. During this period, timely and systematically supportive treatment, including mechanical ventilation combined with continuous blood purification , vasoactive drugs and nutritional supplement, Abbreviations: r, correlation coefficient; ARDS, acute respiratory distress syndrome; ARF, acute renal failure; WBC, white blood cells; Scr, serum creatinine; PT, prothrombin time;", "Title: Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies\nPassage: From 'core groups' to 'superspreaders', epidemiologists have long recognized the immense potential of targeting high-risk groups for efficient control of infectious diseases . These groups are often described by the classic '80/20 rule' where 20% of the individuals drive 80% of disease transmission and thus dominate the overall pattern of disease prevalence. For sexually transmitted and blood-borne infections such as Hepatitis C , syphilis , and HIV-1 , superspreading is driven by high-risk sexual or needle-sharing behaviors. For many other pathogens, spanning a broad range of transmission modes and life histories, superspreading plays an important role in transmission dynamics but Title: Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever", "Passage: Super-spreaders are individuals who can infect a disproportionately large pool of susceptibles . Here, super-spreading events are identified and quantified by analyzing how the effective reproduction number is distributed. The distribution of the individual effective reproduction numbers for the Jos and Zorzor outbreaks, based on the 100 permutations of the duration of illness, is shown in Fig. 5 .A. Although 85% of the predictions for individual R Nos Ind v1, there is a fat tailed distribution, with extreme values of R Nos Ind v12. Similar patterns are observed for KGH cases for the individual effective reproduction number R Ind . Title: Enhancing genetic disease control by selecting for lower host infectivity and susceptibility\nPassage: designated super-spreaders. Title: Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies", "Passage: Targeting these superspreader subpopulations for therapeutic or preventive measures would tremendously increase the efficacy of disease control , while failure to target high-risk groups weakens efforts to achieve 'herd immunity' by vaccination and severely limits the ability to reduce disease at the population level . Unfortunately, identifying these crucial high-risk populations requires in-depth knowledge of the social or sexual networks that underlie disease spread, which is rarely attainable , as well as knowledge of as-yet unknown biological correlates of risk. Further aggravating the problem of targeting superspreaders are: nonhealthseeking behaviors in the key populations, such as injection drug users ;", "Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation\nPassage: To explore a possible function for the IFITM family in CD4 + T-cell activation or differentiation, we first measured expression of the Ifitm genes by RNA sequencing from CD4 + T cells for a 24 h time course following in vitro activation with anti-CD3 and anti-CD28 in Th0/Th1/Th2 skewing-conditions . This time-course analysis showed that Ifitm1 was expressed at low levels throughout the time course in all conditions. At the start of the experiment, Ifitm3 was most highly expressed of the three genes, but it was then rapidly downregulated after 4 h in response to the TCR/CD28 stimulus. In contrast, Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation", "Passage: Given the function significance of IFITM family deletion on the transcriptome of resting CD4 + T cells, we next investigated Ifitm expression in FACS-sorted na\u00efve WT CD4 + T cells by RNA sequencing, after anti-CD3/CD28 activation over a longer 30-h time course . At 30 h after activation, expression of Ifitm2 was more than tenfold higher than Ifitm1 and Ifitm3. As expected, expressions Ifitm5 and Ifitm6 were very low. Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation\nPassage: In tissue culture experiments, IFITM proteins enable cells to resist infection by both enveloped and nonenveloped viruses, and several distinct mechanisms have been proposed to explain their ability to increase cellular resistance to different viruses . Title: IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation", "Passage: Many studies have shown that the IFITM family provides cellular resistance to viral infection in vitro, and GWAS identified IFITM3 as a resistance gene for influenza in humans . However, we show here that deletion of IFITM proteins reduces the severity of Th2 inflammation in a mouse asthma model, suggesting an evolutionary balance between conferring cellular viral resistance and susceptibility to allergic disease. This study demonstrates that the IFITM family of proteins should be viewed not only as essential proteins for cellular resistance to viral infection but also as important regulators of CD4 + Th cell differentiation and function.", "Title: Epidemiology, Seasonality and Treatment of Hospitalized Adults and Adolescents with Influenza in Jingzhou, China, 2010-2012\nPassage: of patients were admitted to the ICU during their hospitalization. Corticosteroids such as lowdose hydrocortisone are only recommended for critically ill patients with suspected adrenal insufficiency or refractory septic shock ; since it is unlikely that a substantial proportion of our patients had these complications, corticosteroid treatment of both influenza positive and negative SARI patients was probably overused. Further studies, guidelines, and education of physicians about the harms of corticosteroid use in SARI and influenza patients are needed in China. Title: Host resilience to emerging coronaviruses", "Passage: SARS-CoV outbreak, many different treatment options were empirically tried on human patients. One immunomodulatory treatment that was tried during the SARS-CoV outbreak was systemic corticosteroids. This was tried with and without the use of type I IFNs and other therapies that could directly target the virus . Retrospective analysis revealed that, when given at the correct time and to the appropriate patients, corticosteroid use could decrease mortality and also length of hospital stays . In addition, there is some evidence that simultaneous treatment with IFNs could increase the potential benefits . Although these treatments are not without complications, and there Title: Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis", "Passage: above accounts, corticosteroids were used in 40 to 53% of patients with confirmed or probable H1N1 virus infection with various dose regimens , and about 22% of inpatient children with H1N1 were treated with corticosteroids . Corticosteroids were empirically used as a preferred or lifesaving treatment and were observed in more than 50% of the severe patients, including acute respiratory distress syndrome, during the pandemic influenza in 2009 . Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: that corticosteroid use was significantly associated with ICU mortality . Meta-analyses of observational studies have concluded that that corticosteroid treatment of hospitalized influenza patients does not result in better outcomes and may be associated with adverse outcomes including increased mortality . Similarly, a retrospective observational study conducted on critically ill children during the 2009 H1N1 pandemic found that high-dose corticosteroid treatment was associated with mortality in the ICU, although a causative relationship was not determined . A selection of individual observational studies in critically ill children and adults have also reported potential association between corticosteroid treatment and adverse influenza outcomes", "Title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations\nPassage: All sequences are available in GenBank from which whole genome data were retrieved and aligned, and ITR sequences extracted. This resulted in a data set of ITR sequences ranging from 116 to 209 bases, as lengths were variable among the types. A subset of sequences spanning the first 1-66 bases that included the conserved HAdV viral replication sequence motifs were selected for detailed analysis. Title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations", "Passage: Nasopharyngeal swab specimens were collected from both outpatients and inpatients who presented with flu-like symptoms, and are archived at Queen Mary Hospital . Adenoviruses were detected by PCR and were identified further by molecular typing using partial sequence data from the hexon and fiber genes, as previously reported . Then, 10 virus strains that were identified as type 4 were cultured in human lung cell lines , and genomic DNA was extracted using the Viral DNA Extraction Kit from Omega Bio-Tek, Inc. , as previously noted . Title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations\nPassage: Genome sequence data were accessed from GenBank. HAdV-E4 genomes include RI-67 or \"prototype\" ; CL68578 or \"vaccine\" ( Title: Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children", "Passage: genomic DNA was used for random amplification as previously described 22 , the amplified DNA was used as a template for Illumina HiSeq2500 sequencing , following the next-generation sequencing protocol of Beijing Berry Genomics. The complete genome of HAdV was assembled by SOAPdenovo 23 , SeqMan software and annotated based on the annotation of the HAdV-C prototype strain .", "Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus\nPassage: have confirm that N-terminal TAP-tag did not interfere with Tat function nor its localisation in Jurkat cells, when compared to untagged-Tat. Of note, Tat subcellular distribution can vary according to the cell type employed. While Tat is known to accumulate in the nucleus and nucleolus in Jurkat cells and other transformed cell lines, in primary T-cells, Tat was described to primarily accumulate at the plasma membrane, while trafficking via the nucleus where it functions . These differences remain to be characterised but could be related to different expression levels of transport factors in transformed cell lines versus primary cells, as Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: analysis . TAP-Tat displayed a prominent nuclear/nucleolar localization but could also be detected in the cytoplasm. These observations were further validated by immunofluorescence microscopy . Of note, Jurkat-tat presented similar patterns for Tat subcellular distribution as shown by immunofluorescence microscopy and subcellular fractionation followed by WB analysis . We next compared the growth rate and proliferation of the Jurkat TAP and TAP-Tat cell lines , which were equivalent . Similarly, FACS analysis confirmed that the relative populations in G1, S, and G2/M were similar for Jurkat TAP-Tat and TAP cells . Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: The mechanisms of Tat-mediated segregation and compartimentalisation of proteins in or out of the nucleolus may depend on factor inherent for each protein and the nature of their relationship with Tat, since subcellular fractionation combined with WB analysis showed that the pattern and extent of subcellular redistribution between proteins varied. We could observe cases where Tat upregulated the expression of proteins which resulted in a general increase of theses proteins throughout the cellular compartments including the nucleolus . Alternatively, Tat could trigger the nucleolar translocation of proteins directly from the cytoplasm or the nucleoplasm . Additionally, we observed cytoplasmic proteins Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: STAT3. The transcription factor signal transducer and activator of transcription 3 was significantly enriched in the nucleolar fraction by Tat constitutive expression. Furthermore, WB analysis indicated that Tat expression could promote the relocalisation of STAT3 from the cytoplasm to the nucleus, with a distinct enrichment in the nucleolus . Interestingly, previous studies have demonstrated Tat-mediated activation of STAT3 signaling, as shown by its phosphorylation status . Interestingly, STAT3 phosphorylation induced dimerisation of the protein followed its translocation to the nucleus .", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: 5. Health Commission of the People\u2019s Republic of China.. The notification of the trial Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: 4. Health Commission of the People\u2019s Republic of China.. The notification of the trial Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: for SARS and MERS were reported to be safe, well-tolerated and able to trigger the relevant and appropriate immune responses in the participants. In addition, we highlight six ongoing Phase I clinical trials identified in the ClinicalTrials.gov register ); Table S4 ) . These trials are all testing the safety and immunogenicity of their respective MERS-CoV vaccine candidates but were excluded as there are no results published yet. The trials are projected to complete in December 2020 ) and December 2021 ). Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Existing literature search did not return any results on completed 2019-nCoV trials at the time of writing. Among 23 trials found from the systematic review , there are nine clinical trials registered under the clinical trials registry for 2019-nCoV therapeutics . Of which five studies on hydroxychloroquine, lopinavir plus ritonavir and arbidol, mesenchymal stem cells, traditional Chinese medicine and glucocorticoid therapy usage have commenced recruitment. The remaining four studies encompass investigation of antivirals, interferon atomization, darunavir and cobicistat, arbidol, and remdesivir usage for 2019-nCoV patients . Seroconversion measured by S1-ELISA occurred in 86% and 94% participants after 2 and 3", "Title: Molecular Epidemiological Investigation of Porcine kobuvirus and Its Coinfection Rate with PEDV and SaV in Northwest China\nPassage: The genome of this genus consists of a single-stranded positive-sense RNA, ranging from 8.2 to 8.4 kb, including the poly tail . All kobuviruses share essentially the same genomic organization. Nonstructural protein L is encoded at the N-terminus of the polyprotein and is followed by three structural capsid proteins, VP0, VP3, and VP1 and seven nonstructural proteins, 2A, 2B, 2C, 3A, 3B, 3C, and 3D . Title: A Brief Review on Diagnosis of Foot-and-Mouth Disease of Livestock: Conventional to Molecular Tools", "Passage: The viral particle, or virion, contains a single-stranded RNA of positive polarity, approximately 8500 nucleotides long. It is an icosahedral particle with a smooth surface and a diameter of about 30 nm . The fine structure of the virus has been described by X-ray crystallography . There are 60 copies of each of the structural protein VP1, VP2, VP3, and VP4. While the first three structural proteins have surface components, the fourth is internal. The virion is also usually composed of one or two units of VP0, the precursor of VP2 and VP4 . The structural proteins, VP1-3 fold into Title: First Complete Genome Sequence of a French Bovine coronavirus Strain", "Passage: Text: B ovine coronavirus belongs to the Nidovirales order, the Coronaviridae family, the Coronavirinae subfamily, and the Betacoronavirus . Its genome is a single-stranded, linear, and nonsegmented RNA of around 31 kb. BCoV is responsible for respiratory and enteric diseases in cattle, particularly during winter . To date, the 19 complete BCoV genome sequences available in GenBank databases originated from the United States or Asia. Here, we report the first complete genome sequence of a BCoV detected in France. Title: Human Bocavirus: Lessons Learned to Date\nPassage: Recently, Zhao and colleagues showed that the genome of HBoV subtype 2 is circular . This circular nature of the genome raises the question of why the hairpin structures are different between the HBoV subtypes, and it should be determined whether these linker structures are of cellular or other origin.", "Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: and how these influence the process warrant a more in-depth examination. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: The health-evidence.ca registry was used to identify gaps and areas of wealth in the public health review literature. Each of the 21 Focus of Review topic areas were searched, and the quantity and proportion of reviews rated methodologically strong, moderate, and weak were identified. Three categories were used to define availability of reviews within each topic area: few, representing 1-150 reviews; moderate, representing 151-300 reviews; and, many, representing topic areas possessing greater than 301 reviews. Reviews that addressed multiple topics were accounted for within each topic area that they addressed . Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: The 21 Focus of Review topic areas were further broken down into 291 sub-topic categories. There were 34 sub-topics with no reviews available including: hormone replacement therapy, infertility, Norwalk virus, autism, and elder abuse, among others . The 21 Focus of Review topic areas that had sub-topics with no review included adult health, communicable disease/infection, dental health, environmental health, food safety and inspection, parenting, and senior health. The largest proportion of sub-topic with no review was observed within communicable disease/infection . Adult health was ranked sixth and communicable disease/ infection ranked tenth by registered users. Parenting was ranked as a Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: As of April 1, 2011 there were 2, 175 systematic reviews evaluating the effectiveness of public health and health promotion interventions indexed in the health-evidence. ca registry. Table 3 provides an overview of the availability of reviews within each of the 21 Focus of Review topic areas. Figure 3 depicts the relationship between registered users' interests, visitor searches, and available reviews within each of the 21 topic areas.", "Title: Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study\nPassage: In our series, BAL was performed in 89% of patients. Unlike a recent work showing that a lymphocytic BAL fluid was associated with better ICU survival in ARDS patients with no common risk factor, our study failed to identify any predictive role of BAL cytology on hospital survival. BAL fluid analysis does not seem a useful diagnostic tool for AS or aMDA-5 dermato-pulmonary syndromes, but should nevertheless be performed to rule out an alternative diagnosis, such as diffuse alveolar hemorrhage or active infection. Title: Coinfection and Mortality in Pneumonia-Related Acute Respiratory Distress Syndrome Patients with Bronchoalveolar Lavage: A Prospective Observational Study", "Passage: introducing 200 mL of a sterile, warm saline solution into a bronchial subsegment and aspirating it back in four 50-mL aliquots. The BAL samples were analyzed in the hospital's microbiology and pathology laboratories for the presence of bacteria, fungi, and viruses in accordance with normal practice. The bacteria analyzed included aerobic and anaerobic bacteria, legionella, Mycoplasma pneumoniae, and mycobacteria. Urinary antigen testing was performed for the detection of S pneumoniae and L pneumophila . The fungal analysis involved candida culture, an aspergillosis antigen and culture, and P jirovecii testing. The BAL samples were subjected to Giemsa and Gomori methenamine silver Title: Interstitial lung diseases in children", "Passage: In other pathological situations, BAL can usefully serve to direct further investigations. Accumulation of BAL T-lymphocytes with prevalence of CD4+ cells is suggestive of sarcoidosis, whilst prevalence of CD8+ cells is suggestive of hypersensitivity pneumonitis . Also, an increase in BAL eosinophils suggests pulmonary infiltrates associated with eosinophilia syndromes . Depending of the underlying diseases, a number of cellular and molecular investigations can be proposed including the studies of various surfactant components, phospholipids and apoproteins . Title: Interstitial lung diseases in children", "Passage: Bronchoalveolar lavage usefully provides specimens for cytological examination, microbial cultures, and molecular analysis. Besides infections, BAL can be of diagnostic value in several situations. In the context of pulmonary alveolar proteinosis, BAL abnormalities are characterized by milky appearance fluid, abundant proteinaceous periodic acid schiff positive material, and presence of foamy alveolar macrophages . BAL can also be diagnostic for pulmonary alveolar haemorrhage . This diagnostic is easy when the BAL fluid has a bloody or pink color, but its gross appearance may be normal. Microscopic analysis may then be of value by documenting the presence of red blood cells in", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: antigens has led to their inclusion with HA-based vaccines to improve immunogenicity and broaden breadth of both humoral and cellular immunity . However, as both CD8 + T cell and neutralizing antibody responses are generated by the vector and vaccine antigens, immunological memory to these components can reduce efficacy and limit repeated use . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Historically, the HA has not been widely considered as a universal vaccine antigen. However, the recent identification of virus neutralizing monoclonal antibodies that cross-react with many subtypes of influenza virus has presented the opportunity to design vaccine antigens to prime focused antibody responses to the highly conserved regions recognized by these monoclonal antibodies. The majority of these broadly cross-reactive antibodies recognize regions on the stalk of the HA protein . The HA stalk is generally less immunogenic compared to the globular head of the HA protein so most approaches have utilized -headless\u2016 HA proteins as immunogens. HA stalk vaccines have Title: Viral vector-based influenza vaccines", "Passage: To induce sterile immunity against influenza viruses, HA is the surface antigen of choice since it efficiently stimulates B-cell responses and the production of virus neutralizing antibodies in vivo. Therefore, MVA vector vaccines expressing HA of various subtypes have been constructed and tested in animal models. It should be noted however that most antibodies directed to HA are strain-specific and display poor cross-reactivity with HAs of alternative subtypes, or even with HA molecules from other viruses of the same subtype. Therefore, MVA-HA vaccines often offer protection from infection with the homologous influenza A virus, but not or poorly against infection Title: Synthetic carbohydrate-based vaccines: challenges and opportunities", "Passage: With the successful experience in monovalent vaccine development, Danishefsky and Livingston group developed multiple antigens in a one single TACA vaccine. In their Phase II clinical trial, the patients were coadministrated with GM2, Globo H, Lewis y , TF, Tn, STn Tn-MUC1 that was individually conjugated to KLH and mixed with adjuvant QS21 as a heptavalent vaccine. Eight of nine patients developed responses against at least three antigens. However, the antibodies titer was lower than the response from administration of a single corresponding vaccine . The over-dose carrier protein KLH may induce a strong immune response against itself and impair", "Title: Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies\nPassage: that were identified from natural infections, as well as in animal models and bnAb monotherapy human trials . For example,nearly all HIV-1 variants found in recent plasma samples from the original VRC01 donor are now resistant to VRC01 , as are the VRC01-resistant strains we previously identified in a chronically infected patient .Similar to what we found in the current study, the mutations responsible for such resistance are also confined to the area between residues 278 and 283 of Loop D, and to potential N-linked glycosylation sites between residues 458 and 467 of the \u03b223/loop V5/\u03b224 region. Analyses of rebound Title: Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies", "Passage: Collectively, signature mutations that confer resistance to the CD4bs antibodies were located on multiple regions within the CD4bs supersite. Mechanistically, those mutations could act by abolishing hydrogen bonds and/or salt bridges, as shown for mutations at position 97 of gp120 to non-lysine residues and at position 279 to non-Asn/Asp residues. Mutations could also act by imposing steric hindrance to antibody contact, as observed in mutations to amino acids with bulkier side chains from Ala at position 281, Thr at position 455 and Gly at position 471. Altering a potential glycosylation site is another mode of resistance as observed in many Title: Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41", "Passage: 200-fold more potent than the bNAb VRC01, T20, and CD4-Ig, respectively. Furthermore, they have shown higher stability and specificity and a lower aggregation propensity than CD4-Ig. Later, they constructed a 4Dm2m mutant with prolonged half-life in mouse serum . Most recently, we have tested the anti-HIV-1 activity of 4Dm2m in combination with several currently used ARDs, including Zidovudine , Efavirenz , or Saquinavir , and with the gp41-targeting peptides, including T20, T2635, or SFT. We found that all these combinations exhibited synergistic anti-HIV-1 activity against infection by laboratory-adapted and primary HIV-1 strains, including those resistant to NRTIs and peptide-based HIV-1 Title: Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies\nPassage: with quadruple mutations .", "Title: Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families\nPassage: Across the data set as a whole we found that all virus families displayed relatively large tree topological distances with nPH85 values of !0.6, suggesting that cross-species transmission is widespread, at least at the family-level . While all families showed distances at the upper end of the scale, the Hepadnaviridae had the shortest distance , indicating that this family experiences more frequent co-divergence than any other studied here. At the other end of the spectrum both the Rhabdoviridae and Picornaviridae displayed nPH85 > 0.97, indicative of frequent host switching and hence little evidence for virus-host co-divergence. Title: Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families", "Passage: extinction and host-jumping events . the number of viruses and hosts per family and the nPH85 under our tree distance metric, this result implies that sampling more viruses increases the likelihood of detecting host jumping events. In addition, we found that DNA viral families had, on average, a shorter nPH85 distance than families of RNA viruses . Note that there is no significant difference between the number of viruses in families of DNA viruses compared to those in RNA virus families. In this context it is striking that the five families with the shortest topological distances all possessed DNA genomes. Title: The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members", "Passage: PF04505 is a score of 20.6. The sequence datasets were controlled for annotated pseudogenes and transcript variants from the same gene. In the case of multiple transcript variants, the longest sequence was kept. The resulting non-redundant datasets were used for the analysis. The bacterial sequences were obtained by querying Uniprot for the Pfam ID . Thereafter, the sequence set was downloaded by browsing by taxonomy and restricting it to species with a full proteome set. To assure that no lineages were missing in the selection of proteomes the nr protein dataset from NCBI was downloaded. The nr datasets contained 15,322,545 Title: Human core duplicon gene families: game changers or game players?", "Passage: family in humans is located at the boundary of a common inversion polymorphism of approximately 970 kb at 17q21.31 . This has been shown to be a significant risk factor locus for the tangle diseases, including progressive supranuclear palsy , corticobasal degeneration , Parkinson's disease and Alzheimer's disease , and it is associated with microdeletion syndromes . LRRC37B, a member of the LRRC37 gene family is also a breakpoint for NF1 microdeletion syndrome .", "Title: Patterns of Positive Selection in Six Mammalian Genomes\nPassage: evolutionary time scales can allow phylogenetic methods to more accurately pinpoint the specific locations of functionally important substitutions. In some cases, phylogenetic methods also allow such substitutions to be mapped to particular branches of a phylogenetic tree, thereby providing useful insights about the evolutionary histories of the sequences in question. Title: Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families", "Passage: Another important aspect of assessing virus-host co-divergence is that the evolutionary time-scales of viruses and their hosts are consistent . Although such a comparison is valuable, it is problematic for the present study because high rates of evolution lead to substitutional saturation in virus genomes at a much faster rate than in cellular organisms. Indeed, it is likely that many of the cross-species transmission events implied here have occurred on timescales of many millions of years. As a result, temporal signal is rapidly lost, precluding accurate estimates of their long-term evolutionary time-scales, even though the topology is often accurately recovered Title: Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families", "Passage: here should be extended to a wider range of data sets as they become available, particularly because increased taxon sampling results in a larger tree space and increases the statistical power of these analyses. Title: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics\nPassage: Although we did not explicitly try to address the adequacy of lion subspecies designations , we provided strong evidence that there is no evidence of substantial genetic exchange of matrilines among existing populations as the AMOVA withinpopulation component was uniformly high in all distinct subdivision scenarios . Similarly, significant population structure was detected from nDNA , with low levels of admixture evident from Bayesian analysis . Therefore, employing a bottom-up perspective that prioritizes populations, rather than large-scale units , might preserve and maintain lion diversity and evolutionary processes most efficiently .", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Text: Coronaviruses are spherical, enveloped, and the largest of positive-strand RNA viruses. They have a wide host range, including birds, farm animals, pets, camels, and bats, in which they primarily cause respiratory and gastrointestinal disease. Belonging to the order Nidovirales, family Coronaviridae, and the subfamily Orthocoronaviridae there are four genera of coronaviruses-Alphacoronavirus, Betacoronavirus, Deltacorona virus, and Gammacoronavirus . Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir.", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Childhood pneumonia can also lead to significant morbidity and chronic disease. Early life pneumonia can impair longterm lung health by decreasing lung function . Severe or recurrent pneumonia can have a worse effect on lung function; increasing evidence suggests that chronic obstructive pulmonary disease might be related to early childhood pneumonia . A meta-analysis of the risk of long-term outcomes after childhood pneumonia categorized chronic respiratory sequelae into major and minor groups . The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: pneumonia. Because respiratory diseases affect almost 1 billion people globally and are a major cause of mortality and morbidity , childhood pneumonia might contribute to substantial morbidity across the life course. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Childhood pneumonia and clinically severe disease result from a complex interaction of host and environmental risk factors . Because of the effectiveness of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination for prevention of radiologic and clinical pneumonia, incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: to accessing health care is an important area with the potential to impact the survival and health of the most vulnerable children .", "Title: Viral vector-based influenza vaccines\nPassage: Several different vaccine formulations are available: trivalent or quadrivalent inactivated virus vaccines or live attenuated influenza virus vaccines . Most vaccines are produced in embryonated chicken eggs, but vaccines produced in mammalian or insect cells are also available. Inactivated vaccines are administered intramuscularly or sometimes intradermally and predominantly aim at the induction of serum antibody responses against the viral hemagglutinin and neuraminidase to a lesser extent. Protection from disease is mainly mediated by virus neutralizing antibodies against HA, but NA-specific antibodies also contribute to protective immunity. 1 Currently licensed LAIV are administered locally via nasal spray. Viruses are attenuated by Title: Confronting Potential Influenza A (H5N1) Pandemic with Better Vaccines", "Passage: After initial hesitation about using a wide-scale program of poultry vaccination, some European and Asian countries have begun vaccination. Inactivated vaccines are widely used in poultry but lack of critical potency testing, standardization, and quality control has led to variable and suboptimal immune responses. Moreover, a legitimate concern remains that the fowl vaccinated by attenuated live viruses may survive the disease but still carry the virus; thus, they would continue to spread infl uenza silently at the fl ock level or to humans who come into contact with them. Vaccination that resulted in low levels of seroconversion facilitated the emergence Title: Reverse Genetics Approaches for the Development of Influenza Vaccines", "Passage: Killed virus vaccines or IIV are generally administered intramuscularly and can be classified as whole virus vaccines or split vaccines . Whole virus vaccines were the first to be developed. The influenza virus is grown in embryonated chicken eggs, subsequently purified, concentrated and chemically inactivated with formaldehyde . Whole virus vaccines are safe and well tolerated, with an efficacy of 60%-90% in children and adults. On the other hand, the split-virus vaccine exposes all viral proteins and subviral elements upon dissociation of the virions by a nonionic detergent treatment step . Most influenza vaccines in the U.S. and Europe are Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Currently licensed influenza virus vaccines suffer from a number of issues. The inactivated vaccines rely on specific antibody responses to the HA, and to a lesser extent NA proteins for protection. The immunodominant portions of the HA and NA molecules undergo a constant process of antigenic drift, a natural accumulation of mutations, enabling virus evasion from immunity . Thus, the circulating influenza A and B strains are reviewed annually for antigenic match with current vaccines, Replacement of vaccine strains may occur regularly, and annual vaccination is recommended to assure protection . For the northern hemisphere, vaccine strain selection occurs in", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: the lung tissues of healthy, wild-caught field mice . The virus was later found to represent the type species of a new genus Hantavirus of the family Bunyaviridae, although it was later apparent that the first hantavirus to be isolated was the shrew-borne Thottapalayam virus . The categorization of hantaviruses as belonging to the family Bunyaviridae is due in part to the consistent presence of three RNA genomes that are circularized in vivo as a result of the presence of terminal complementary nucleotides that help fold the genome into a -hairpin\u2016 morphology, first described for the Uukuniemi phlebovirus . Table Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: cases of acute febrile disease with renal compromise were described from several Eurasian countries and Japan, often in association with military engagements . HFRS as a distinct syndrome, however, was first brought to the attention of western medicine in association with an outbreak that occurred among United Nations troops during the Korean conflict between 1951 and 1954, where more than 3,200 soldiers were afflicted . It took more than two decades until the etiologic agent, Hantaan virus , was isolated from the striped field mouse Apodemus agrarius, detected in part by the binding of antibodies from patient serum samples to Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Human infection by hantaviruses is thought to follow contact with secretions or excretions produced by infected rodents. In the United States, 538 human infections by hantavirus were reported through late December 2009 , with New Mexico, Arizona and Colorado exhibiting the highest case-loads. While the prototypical central American hantavirus in central America was Rio Segundo virus of Reithrodontomys mexicanus from Costa Rica, the first human disease appeared some years later in Panama, where Choclo virus arose as the etiologic agent and is believed to be responsible for all known cases of HCPS. The fulvous pygmy rice rat Oligoryzomys fulvescens has Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: of human hantavirus infections in Central America. In South America, the first largest identified outbreak occurred in the Chaco region in northwestern Paraguay during 1995-1996. Seventeen individuals were identified with SNV antibody or were antigen positive out of 52 suspected cases . Major outbreaks due to ANDV occurred in 1996 in southern Argentina ; in southern Chile clusters of patients presented with hantavirus illness in 1997 . In Brazil, the first outbreak was identified in the Brazilian Amazon in 2000, and involved small villages that resulted in a 13.3% prevalence of those tested .", "Title: Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset\nPassage: This, in conjunction with the small size of marmosets, their immune response to infection that is comparable to humans, and the ability to house more statistically relevant numbers within high containment, makes the marmoset an appropriate animal model for biodefense-related pathogens. Title: Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset\nPassage: This, in conjunction with the small size of marmosets, their immune response to infection that is comparable to humans, and the ability to house more statistically relevant numbers within high containment, makes the marmoset an appropriate animal model for biodefense-related pathogens. Title: Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset", "Passage: Marmosets have been used to model the infection syndrome caused by a number of public health pathogens including Lassa virus , Hepatitis C virus , Dengue virus , Herpesvirus , Junin virus Rift Valley Fever , and SARS . Marmosets have also been used to model a number of biodefense pathogens including Eastern Equine Encephalitis virus , Bacillus anthracis , Francisella tularensis , Burkholderia pseudomallei , Marburg haemorrhagic fever virus , Ebola haemorrhagic fever virus , and Variola virus . The utility of marmosets to assess medical countermeasures has also been demonstrated; a vaccine has been tested for Lassa fever Title: Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset", "Passage: Marmosets have been used to model the infection syndrome caused by a number of public health pathogens including Lassa virus , Hepatitis C virus , Dengue virus , Herpesvirus , Junin virus Rift Valley Fever , and SARS . Marmosets have also been used to model a number of biodefense pathogens including Eastern Equine Encephalitis virus , Bacillus anthracis , Francisella tularensis , Burkholderia pseudomallei , Marburg haemorrhagic fever virus , Ebola haemorrhagic fever virus , and Variola virus . The utility of marmosets to assess medical countermeasures has also been demonstrated; a vaccine has been tested for Lassa fever", "Title: Viral vector-based influenza vaccines\nPassage: Alphaviruses are single-stranded RNA viruses with a positive sense genome of the Togaviridae family. Several alphaviruses are being developed as vaccine vectors, including semliki forest virus , sindbis virus and Venezuelan equine encephalitis . These vectors often are replication deficient replicons that do not encode viral structural proteins, as these regions of the genome are replaced by transgenes of interest. Viral RNAs are self-replicating and are capable of transgene expression at high levels. 98 As an added advantage, when using alphavirus replicons pre-existing immunity to the vector should not pose a problem and multiple sequential vaccinations are a possibility. Furthermore, Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Alphaviruses are positive-sense, single-stranded RNA viruses of the Togaviridae family. A variety of alphaviruses have been developed as vaccine vectors, including Semliki Forest virus , Sindbis virus, Venezuelan equine encephalitis virus, as well as chimeric viruses incorporating portions of SIN and VEE viruses. The replication defective vaccines or replicons do not encode viral structural proteins, having these portions of the genome replaces with transgenic material. Title: Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity", "Passage: for VSRs 26, 27 . Alphaviruses are member of arboviruses containing 27 recognised members 28 with a very wide geographic distribution and several geographical variants on the basis of which they have been classified as Old World and New World viruses 29 . Grouped into seven complexes based on serological cross-reactivity, they infect a variety of host including birds, fishes, mammals including humans and are maintained in natural cycles by transmission between susceptible vectors and vertebrate hosts 30 . Alphaviruses have a single plus-stranded RNA genome encapsulated by capsid proteins. The approx. 12 kb genome consists of two open reading Title: Viral vector-based influenza vaccines", "Passage: Another alphaherpesvirus of poultry, turkey herpesvirus has also been extensively studied as influenza vaccine vector in chickens. HVT encoding the HA gene of an A virus afforded protection from infection with various A viruses. Similarly, a recombinant HVT-H7 vaccine protected chickens against infection with the homologous A virus. 125 Since chickens are often vaccinated at very young age , maternal antibodies against the vector or against the protein encoded by the transgene could influence vaccine efficacy. Interestingly, HVT was shown to be immunogenic even in the presence of these maternal antibodies. 126 Marek's disease virus , an alphaherpesvirus closely related", "Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?\nPassage: The pneumococcus is a typical colonizer of the human nasopharynx. About 20-50% of healthy children and 8-30% of healthy adults are asymptomatically colonized . Pneumococci cause diseases ranging from mild, i.e., sinusitis, conjunctivitis, and otitis media, to more severe and potentially life-threatening infections, including communityacquired pneumonia, bacteraemia, and meningitis . This bacterium is associated with high morbidity and mortality rates in risk groups such as immunocompromised individuals, children, and elderly . Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: The pneumococcus is a typical colonizer of the human nasopharynx. About 20-50% of healthy children and 8-30% of healthy adults are asymptomatically colonized . Pneumococci cause diseases ranging from mild, i.e., sinusitis, conjunctivitis, and otitis media, to more severe and potentially life-threatening infections, including communityacquired pneumonia, bacteraemia, and meningitis . This bacterium is associated with high morbidity and mortality rates in risk groups such as immunocompromised individuals, children, and elderly . Title: Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection\nPassage: average vaccination coverage with pneumococcal conjuagate vaccine is estimated to be 60-65% through the private market. Title: Vaccination against Paediatric Respiratory Pathogens", "Passage: In healthy children, nasopharyngeal colonization with respiratory bacteria is a prerequisite for the development of respiratory or invasive diseases . Asymptomatic transient nasopharyngeal colonization with bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, is common and decreases with age and the maturation of the immune system. Geographic region, ethnicity, season, day-care attendance, environmental factors and previous vaccinations are important determinants of bacterial colonization .", "Title: How necessary is a fast testkit for mitigation of pandemic flu?\nPassage: We measured the severity of the pandemic using two key indicators-total attack rate and peak attack rate . The total attack rate indicates the total number of people who display influenza-like symptoms due to the novel strain. It is not the same as the total number of people infected as there is a fraction of people who recover without showing any symptoms. The peak attack rate measures the highest number of people showing symptoms due to the pandemic virus infection. It is an indication of the maximum burden on the healthcare system, as well as a partial reflection of the Title: Quantifying social distancing arising from pandemic influenza", "Passage: Having estimated the values ofR\u00f0B\u00de andR\u00f0F\u00de, equation establishes a unique relationship between a and s. The reported clinical attack rate is the obvious first choice as an estimate of a, but may be biased for several possible reasons: it is conceivable that clinical cases may not have conferred solid immunity, cases that seroconvert may be asymptomatic, and illness may have been mistakenly attributed to influenza when it was in fact caused by another influenza-like illness . Hence, we explore the values of a to be an arbitrary 10% below and 10% above the reported clinical attack rate. The upper value Title: Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015\u20132016", "Passage: clinical attack rate was 39% in a typical household in Martinique . The overall attack rate of ZIKV in the island population was estimated at 50% Household Size . C) Observed and expected secondary clinical attack rate in households recruited in the study as a function of household size in the data and for the baseline and the frequency-dependent models. D) Expected secondary clinical attack rate in a typical household in Martinique, as function of household size . The secondary clinical attack rate is the proportion of household contacts who exhibit symptoms. Predictions are given for the baseline and the Title: Quantifying social distancing arising from pandemic influenza\nPassage: Setting the serological attack rate to the observed clinical attack rate of 0.366 estimates the initial susceptible proportion to be sZ0.912 andR 0 Z 1:76 .", "Title: Networks and the Epidemiology of Infectious Disease\nPassage: In general, networks are not necessarily connected; in other words, all parts of the network are not reachable from all others. The component to which a node belongs is that set of nodes that can be reached from it by paths running along edges of the network. A network is said to have a giant component if a single component contains the majority of nodes in the network. In directed networks , a node has both an in-component from which the node can be reached and an out-component that can be reached from that node. A strongly connected component is Title: Networks and the Epidemiology of Infectious Disease\nPassage: of the next-generation matrix Title: Networks and the Epidemiology of Infectious Disease\nPassage: that we expect from disease networks although it is unclear if such simple formulations can be truly representative. Title: Characterizing and controlling the inflammatory network during influenza A virus infection", "Passage: Construction of a rough network. Interactions between these 90 proteins were collected from four PPI databases, including the Biomolecular Interaction Network Database 51 , Human Protein Reference Database 52 , Biological General Repository for Interaction Datasets 53 and Search Tool for the Retrieval of Interacting Genes/Proteins 54 . Finally, we obtained a PPI network with 90 nodes and 412 edges .", "Title: Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study\nPassage: In this cohort, highest serum IP-10 levels were identified among patients with both several pathogen detected and severe pneumonia, suggesting a significant role of IP-10 on pneumonia pathogenesis. Indeed, high plasma levels of IP-10 have previously been reported in patients with sepsis 12 , and were associated with high mortality rate, especially among patients with CAP 34 . Additionally, the IP-10-CXCR3 axis has been related to acute immune lung injury and lymphocyte apoptosis during the development of severe acute respiratory syndrome 35, 36 . Moreover, an in vivo study that modeled influenza and pneumococcal superinfection in mice indicated that pro-inflammatory Title: Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study", "Passage: infections and IP-10 may play major, interconnected roles in the pathogenesis of pneumonia. Clinically, assessment and monitoring of induced IP-10 serum level may assist clinicians to improve diagnosis and patient management of severe community-acquired pneumonia. Title: Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study", "Passage: chemokines, including IP-10, play a crucial role in influenza-induced susceptibility to lung neutrophilia, severe immunopathology and mortality 37 . In this study, markedly elevated IP-10 combined with the highest PCT level were quantified in the serum sample of a child who died, in whom S. pneumoniae was identified in the blood and co-detected with Haemophilus influenzae type B in nasal aspirate. These observations suggest an interrelationship between co-detection, elevated serum IP-10 and the pathogenesis of pneumonia. Title: Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study", "Passage: pneumonia severity. Cases that died during the study, or who had at least one additional clinical signs including central cyanosis, dullness to percussion during chest examination, prostration/lethargy, pleural effusion observed on chest radiography were retrospectively included in the severe pneumonia group. Patients without any of these additional clinical signs were included in the non-severe pneumonia group. Table 4 . a IP-10 values are expressed in pg ml -1 . IP-10 concentration differences between groups were compared using unpaired Mann-Whitney tests; significant changes are in bold. Clinical and molecular analysis. Nasopharyngeal aspirates and whole blood samples were collected from children within", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: The spotting concentration of the capture antibodies varied from 0.2 to 0.0125 mg/ml . The efficacy of the spotting concentration of the capture antibodies was evaluated by virus culture detection, the proper spotting concentration was determined by a combination of minimized cross reaction and higher signal intensity. Figure 1 illustrates the array layout and Figure 2 demonstrates the result of the three spotting buffers and spot concentration of antibody 2B5 by TBE virus culture detection. Cross reaction detection was also conducted by applying JEV, YF, and DV cultures. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: When spotting, different spotting buffers and concentrations of capture monoclonal antibodies were evaluated to optimize the ELISA-array assay. The optimization was evaluated by dot morphology and signal intensity. The tested spotting buffers included 1 \u00d7 phosphate buffer saline , PBS +20% glycerol, and 1 \u00d7 PBS + 20% glycerol+0.004% Triton-X100. A range of monoclonal antibody concentrations were compared. Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses\nPassage: ensure full sequence coverage of the protein. The results revealed that a concentration of 4 M yielded the highest sequence coverage . Thus, this concentration was used in the subsequent experiments using IgG samples. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: for printing than for coating ELISA plates. Coating of a single well in microtiter plate requires 100 \u03bcl of a 1 \u03bcg/ml antibody solution, which is equivalent to 100 ng of IgG. For the ELISA-array, only 30 nl of a 50 \u03bcg/ml antibody solution is required for each spot, which is equivalent to 1.5 ng of IgG. With the characteristics of ease of use, sensitivity, specificity, and accuracy, the ELISA-array assay would be widely accepted for clinical use.", "Title: Tight junctions in pulmonary epithelia during lung inflammation\nPassage: factor and monocyte chemotractant protein 1 . The response to proteolytically active allergens involves storeoperated Ca 2+ entry in epithelial cells , and it should be noted that bacterial exotoxins also activate store-operated Ca 2+ entry . Other factors, which belong to dangerassociated molecular patterns , like adenosine , prostaglandin or histamine , initiate IL-1\u03b2, IL-6, IL-8 and GM-CSF production and release. Further, stimuli for chemokine release from airway epithelial cells are inhaled air pollutants and cold . More recent investigations revealed airway epithelial cells as a source of IL-25, IL-33 and thymic stromal lymphopoieitin . This subset of cytokines Title: Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia", "Passage: Determination of GFP + epithelial cells in vitro. Epithelial cell sheets were fixed with 4% paraformaldehyde and washed in PBS. The Costar filter inserts were cut from the plastic support, placed onto a microscope slide, and mounted with Vectashield Mounting Media with DAPI. Using a Leica CTR6500 confocal microscope, images of six random fields from each filter were captured at \u00d720 magnification. Manual counts were performed by enumerating the blue nuclei and GFP + cells. All epithelial cells within these six fields were counted. For determining the percentage of positive cells, the numerator was the number of GFP + cells Title: Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia", "Passage: T he airway epithelium is a critical interface between the host and environment and a common site of genetic and acquired disease states such as asthma, chronic obstructive pulmonary disease, cystic fibrosis , and infectious diseases. Modifying airway epithelia with therapeutic proteins, gene expression cassettes, or genome-editing reagents offers great promise, but efficacious delivery is a common challenge. This is because the respiratory epithelium presents barriers through its specialized cell types, secreted host defense factors, and mucociliary transport 1 . While in vivo delivery with vector systems has advanced 2-7 , airway epithelia remain poorly transduced by many viral and Title: Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia", "Passage: Note that the two main surface epithelium cell types in the large and small airways of mice are ciliated cells and secretory club cells 1 . Goblet cells are very infrequent in healthy lab mice. We deduced that any surface epithelial cell that was GFP positive and not positive for acetylated alpha-tubulin or Muc5AC was a secretory club cell. Our analysis was for the total number of positive cells and we did not further enumerate the % of ciliated cells that were positive, the % of goblet cells that were positive, etc. Figure 3 , the authors delivered the CPP-ELD", "Title: DGV: Dengue Genographic Viewer\nPassage: Asian I was predominant in Thailand, whereas genotype Asian American was predominant in Cambodia and Vietnam . From 2001, Asian I increased in Cambodia and Vietnam until finally in 2007 Asian I became the predominant genotype in Indochina. The genotype Asian I viruses in Thailand seemed to be widely disseminated into Vietnam via Cambodia but did not reach Malaysia and Bangladesh . Thus, the Asian American genotype was replaced by Asian I in Cambodia and Vietnam between 1998 and 2011. This example also suggests the idea of genotype transition, which probably reflects the mosquito vector habitat and human activities in Title: DGV: Dengue Genographic Viewer", "Passage: We also found a timeline change in the predominant genotypes. From 1998 to 2007, the dominant genotype in Asia was Cosmopolitan, although India-Pakistan-Sri Lanka and Southeast-Oceania belonged to different lineages . The major genotypes in the Indochina countries were different from those of the other Asian countries; genotype FIGURE 4 | A screenshot of the DENV sequence similarity search. An Env sequence derived from an autochthonous case in Japan was used as a sample query. The query was assigned as the Env region of DENV-1 genotype I. Title: DGV: Dengue Genographic Viewer", "Passage: Intriguingly, when focusing on the genotype instead of the serotype, the data from 2000 to 2014 showed at least three potential geographical genotype distribution border lines in Asia . The first border is between the American continents and other regions , the second is located between Bangladesh and Myanmar for the genotype distributions of DENV-1 and -2 and India and Myanmar for DENV-3, and the third is located between Indochina and the Malay Peninsula . There seem to be differences in the DENV-1 and -3 distributions between Malaysia, Singapore and Indonesia; however, the border line is not clear because Malaysia Title: Dating the time of viral subtype divergence", "Passage: For the divergence between subtypes A-H3N2 and B, previous studies using the MCA generally place a time of divergence of several hundred years ago, ranging from the 16th to early 19th centuries. Other analysis have yielded estimates of 3600 years ago . In the current study, application of the MCA yielded estimates in the last half of the 18th century. However, applying the pairwise rate estimate developed above we find uniformly, across genes, that the divergence likely occurred in the very early 20th century. The discrepancy between these two measures is likely due to the increased modeling flexibility of the", "Title: Apoptotic signals induce specific degradation of ribosomal RNA in yeast\nPassage: corresponding fragments in the wild-type strain . In contrast, positions of cleavages at site +610-611 are not affected by mutations in the exosome . This suggests that the cytoplasmic exosome may contribute to rRNA decay by digesting 3 0 ends of at least some cleavage products. Title: Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection", "Passage: turnover rate are likely to be precluded. Mutations of a ribozyme's X-motif using error-prone PCR were used to generate a library of ribozyme mutants . Individual variants were compartmentalised into monodisperse droplets along with fluorogenic substrates. In FADS, each step is uncoupled which is suitable for directed evolution of most ribozymes working in intermolecular reactions or multiple turnover conditions . The selected ribozyme variant exhibited a 28-times greater activity than the original ribozyme. Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: The selected ribozymes were able to replicate, cleave, join, and form peptide bonds. They can polymerize progeny chemically, allow for mutations to occur and can evolve. One molecule serves as catalyst, the other one as substrate. Replication of ribozymes was demonstrated in the test tube . Ribozymes can form peptide bonds between amino acids . Thus, small peptides were available by ribozyme activity. Consequently, an RNA modification has been proposed as peptide nucleic acid , with more stable peptide bonds instead of phosphodiester bonds . Replication of RNA molecules can be performed chemically from RNA without polymerase enzymes. In addition, Title: Apoptotic signals induce specific degradation of ribosomal RNA in yeast", "Passage: Each of the applied apoptosis-inducing conditions resulted in a clear-cut pattern of the 25S degradation intermediates or products. This points to the endonucleolytic nature of the reactions, though exonucleolytic destruction, with certain RNA fragments temporarily protected by compact structures or tight interactions with proteins, cannot be excluded. However, mapping 5 0 and 3 0 boundaries of the major H 2 O 2 -induced cleavage product by primer extension and 3 0 RACE, respectively, confirmed that both ends strictly overlap and thus result from the endonucleolytic cut.", "Title: The immunoregulatory and allergy-associated cytokines in the aetiology of the otitis media with effusion.\nPassage: and secretion of the pro-inflammatory cytokines tumour necrosis factor -a, IL-1 and IL-8, 19 \u00c1 21 deactivate inflammatory macrophages and lead to suppression of acute inflammation. IL-4 can also induce switching of acute inflammation in the chronic stage owing to its ability to up-regulate expression of the mannose receptor on activated macrophages. 22 The mannose receptor promotes fusion of activated macrophages and formation of giant multinucleated cells in the zone of inflammation 23 that create the cellular background for manifestation of chronic inflammation. Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: As discussed, cytokines such as IL-4, IL-13 and IL-10 can boost protein production in mucin-secreting goblet cells. 54, 75, 76 There are several reports of correlations of cytokine levels with disease; however, limited research has been done on the direct effect of cytokines on protein biosynthesis. Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: discovered that cytokine regulation of cellular stress is common to multiple epithelial cell types including intestinal and respiratory epithelial cells. In contrast, cytokines, such as IL-10 and IL-22, suppress ER stress and UPR activation, leading to increased mucus production, improved barrier function and attenuated intestinal mucosal inflammation in experimental colitis models. 52, 54 Immunity regulates protein production and secretion by non-immune cells by indirectly modulating the UPR . As an instructive example of the ability of cytokines to modulate protein production, recent studies in our laboratory show that in chronic infection , the amount of ER stress and consequent Muc2 Title: Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response", "Passage: the proinflammatory cytokines IL-1\u03b2 and IL-6 is triggered by the ER stress inducers thapsigargin and tunicamycin or LPS in a GSK-3\u03b2-dependent manner. However, TNF-\u03b1 is regulated by IRE1\u03b1-mediated XBP1 splicing, independently of GSK-3\u03b2 . These findings provide evidence for previously uncharacterized functions for GSK-3\u03b2 on ER stress in the regulation of the immune response.", "Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection\nPassage: mice is shown in the lower right of each plot. Infected, untreated mice showed clear signs of sickness around day 4-5 after infection and perished by day 8-9. Prophylactic treatment is shown on the left for comparison. Antibody treatment conferred significant protection as determined by comparison of weights in untreated versus prophylaxis and at the time of treatment versus 12 d after infection . The log-rank test indicated significant survival as well . Figure shows one representative experiments of at least three independent repeat experiments. Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection", "Passage: mice showed clear signs of sickness \ue07a4-5 d after infection and perished by day 8-9. Figure shows one representative experiments of at least three independent repeat experiments. Antibody treatment conferred significant protection as determined by comparison of weights in untreated versus prophylaxis, and at the time of treatment versus 12 d after infection . The log-rank test indicated significant survival as well . seroconversion, or by the presence of highly potent antibodies, such as EM-4C04, whose activities were less likely to titer out. The highly specific nature of the response from this patient may have contributed to this advantage, ultimately Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection", "Passage: determine the therapeutic efficacy of the mAbs, mice were challenged with 3xLD50 of the mouse-adapted pandemic H1N1 virus. At various times after infection mice were treated intraperitoneally with 200 \u00b5g of the specific mAbs. All mice were monitored daily and the body weight changes were registered daily as described above. Title: Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid", "Passage: To determine the titre of antibody subclasses in mouse sera, the same procedure as described above was used until the detection step, where 100\u03bcl of rat anti-mouse IgG1 or IgG2a specific antibody was added to each well. ELISA plates were incubated with subclassing antibodies for 1 hour at 37C. Unbound antibody was removed by washing plates 10 times in PBST. Bound subclassing reagents were then detected by adding 100\u03bcl of goat anti-rat antibody, conjugated to HRP , to each well and incubation at 37C for 1 hour. Plates were then washed 10 times with PBST and developed as described above.", "Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: Other bacteria that were developed as DNA vaccine carriers include Listeria monocytogenes , Shigella spp. , and Yersinia enterolica . Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: in vivo was confirmed by the delivery of plasmid by L. lactis to murine epithelial membrane cells, and the protein was effectively expressed by the mammalian cell expression system . Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Briefly, as a DNA vaccine carrier, bacteria are divided into two major groups: non-pathogenic bacteria and attenuated pathogen bacteria. The attenuated bacteria that have been studied as the DNA vaccine carrier include Salmonella spp. , Yersinia enterocolitica , Shigella spp. , and Listeria monocytogenes . Pathogen bacteria target the mucous membranes as their infection route and as a result, they are suitable for mucosal administration. However, the main disadvantage includes the likelihood of causing infection, particularly in infants and immunocompromised patients . Therefore, non-pathogen bacteria such as lactic acid bacteria may be preferable for development as DNA vaccine carriers. A Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Briefly, as a DNA vaccine carrier, bacteria are divided into two major groups: non-pathogenic bacteria and attenuated pathogen bacteria. The attenuated bacteria that have been studied as the DNA vaccine carrier include Salmonella spp. , Yersinia enterocolitica , Shigella spp. , and Listeria monocytogenes . Pathogen bacteria target the mucous membranes as their infection route and as a result, they are suitable for mucosal administration. However, the main disadvantage includes the likelihood of causing infection, particularly in infants and immunocompromised patients . Therefore, non-pathogen bacteria such as lactic acid bacteria may be preferable for development as DNA vaccine carriers. A", "Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China\nPassage: The employed recombination detection methods revealed that SAIBK is a chimera virus, with recombination by the SC021202 strain as a major parent and the H120 vaccine strain as a minor parent. The first and second recombination regions were located at positions 7231 to 9126 and 13437 to 14473 in genes 1a and 1b, respectively. There were two other recombination regions detected at positions 951 to 1067 and 5393 to 5605 of SAIBK, which were recombined with the SC021202 strain as a major parent and the H52 vaccine strain as a minor parent. The recombination detection results suggested that SAIBK is Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China", "Passage: The genome sequence of SAIBK shows the highest identity to the Chinese IBV strain SC021202 and the lowest identity to two Chinese IBV strains, BJ and DY07 . It has lower nucleotide identities of 88.1%, 87.9%, and 87.7% to the most popularly used IBV vaccine strains, H120, H52, and M41, respectively. Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China\nPassage: Phylogenetic analysis of the complete genome results indicated that the SAIBK strain clusters into the same branch as the IBV YN strain and the SC021202 strain . The S1 subunit of the IBV genome is the major determinant of serotype , and S1 analysis indicated that the SAIBK strain has a 4/91-like serotype. Title: A barnavirus sequence mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis", "Passage: to that of MBV . Based on similar genome sizes, coding organizations, and P2-and P3-region sequence similarities, both MBV and RsBV1 appear to be most closely related to plant viruses in the unassigned genus Sobemovirus .", "Title: Species C Rotaviruses in Children with Diarrhea in India, 2010\u20132013: A Potentially Neglected Cause of Acute Gastroenteritis\nPassage: Total RNA from suspended diarrheic stool samples was isolated using Qiazol reagent following the manufacturer's protocol and quantified on a Nanodrop spectrometer . Extracted RNA was used to prepare a pool of first-strand cDNA by random-priming reverse transcription using recombinant MMLV-RT and random hexamer at 37 \u2022 C. Enzymatic activity of the MMLV-RT was stopped by keeping the cDNA reaction mixture at 80 \u2022 C for 3 min. Title: Species C Rotaviruses in Children with Diarrhea in India, 2010\u20132013: A Potentially Neglected Cause of Acute Gastroenteritis", "Passage: plasmid Miniprep kit . Positive recombinant clones were sequenced by the Bigdye terminator Sanger sequencing method in an ABI 3730 x l sequencer . The sequences were deposited in GenBank with Accession Numbers MG553198 , MG553199 and MG553200 . Title: Species C Rotaviruses in Children with Diarrhea in India, 2010\u20132013: A Potentially Neglected Cause of Acute Gastroenteritis", "Passage: The pair-wise similarity among the nucleotide/amino acid sequences were calculated for the VP6, VP4 and NSP4 genes after aligning the sequences by the Clustal V program in MegAlign software of the DNASTAR software package. For the genetic relatedness study, representative fulllength genes of human, cattle, pig, dog and ferret RVC strains were retrieved from the NCBI database . Phylogenetic analysis was performed using the maximum likelihood method in MEGA 6 software . The suitable dendrogram analysis model was identified as described earlier using the find best DNA/protein model tool available in MEGA 6 , confirmed with the FindModel online tool Title: Species C Rotaviruses in Children with Diarrhea in India, 2010\u20132013: A Potentially Neglected Cause of Acute Gastroenteritis", "Passage: The pair-wise similarity among the nucleotide/amino acid sequences were calculated for the VP6, VP4 and NSP4 genes after aligning the sequences by the Clustal V program in MegAlign software of the DNASTAR software package. For the genetic relatedness study, representative full-length genes of human, cattle, pig, dog and ferret RVC strains were retrieved from the NCBI database . Phylogenetic analysis was performed using the maximum likelihood method in MEGA 6 software . The suitable dendrogram analysis model was identified as described earlier using the find best DNA/protein model tool available in MEGA 6 , confirmed with the FindModel online tool", "Title: Introducing the Outbreak Threshold in Epidemiology\nPassage: as the fact that the incubation period is around 5 days, by which point it had easily caused more secondary cases. However, in subsequent outbreaks super-spreaders might not be infected early on, allowing more time to contain the spread. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: a) The mean incubation period was 5.2 days : 4.1-7.0) . We set the same value of the incubation period and the latent period in this study. Thus, \u03c9 P = \u03c9' P = 0.1923. b) There is a mean 5-day delay from symptom onset to detection/hospitalization of a case . The duration from illness onset to first medical visit for the 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days . In our model, we set the infectious period of the cases as 5.8 days. Therefore, \u03b3 P = 0.1724. c) Title: Nanorobot Hardware Architecture for Medical Defense", "Passage: Time for incubation of pandemic syndromes may vary from one contagious plague to another, and first symptoms can be predicted given clinical information and previous historic occurrences, using statistical models. The size of an outbreak is directly correlated and influenced by the delay for recognition about the contaminated area. The incubation period of disease is the time from exposure to the infectious agent to the onset of disease, and depending on the infection dose of influenza, it can vary about 2 to 5 days . For influenza, the contamination can happens through inhalation, ingestion, or direct contact through hand shaking Title: Estimation in emerging epidemics: biases and remedies", "Passage: time until recovery is assumed to be \u0393 and the time to death \u0393 . Furthermore, each individual has an incubation period which is assumed to be similar to the latent period, but with some variation. The incubation period is given by E times a uniformly distributed variable in the interval . It is assumed that a case is reported when symptoms arise. Finally, during the infectious period, new cases are produced with rate 0.34/day, resulting in R 0 = 0.34 \u00b7 5 = 1.7.", "Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features\nPassage: 90% of patients infected with H5N1 are less than 40 years old with a median age of 18 years . The mortality is highest among the 10-19 years age group and lower in people more than 50 years old. The reason for lower infection rate and mortality in older people has not been ascertained. Title: Global Mortality Impact of the 1957\u20131959 Influenza Pandemic", "Passage: Age-specific excess mortality rates were highest at both extremes of the age spectrum . However, when excess mortality was compared to baseline mortality rates, the age groups with highest relative burden were 15-24 years , followed by 5-14 years . In contrast, children aged <5 years and seniors aged \u226565 years only experienced a minor elevation over baseline . The sharp mortality elevation in schoolaged children and young adults was consistent throughout Europe , even though the all-age impact of the pandemic on mortality was generally low in this region. Title: Age- and Sex-Specific Mortality Associated With the 1918\u20131919 Influenza Pandemic in Kentucky", "Passage: The atypically young age distribution of influenza-related deaths in the recent 2009 pandemic of influenza A virus subtype H1N1 infection was more reminiscent of the 1918-1919 pandemic than of later pandemics . Comparison of the age-based mortality risk profiles of the 2 pandemics, however, reveals substantial differences, most notably a peak among adults aged 50-64 years in 2009 . These differences lend further support to biological hypotheses that are unique to the 1918 virus and its historical context. Further comparisons of agebased mortality profiles across pandemics putatively associated with antigenic recycling would be interesting but would require mortality data stratified Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: There were significant differences in the mean age of cases according to the virus type, with a higher prevalence of virus A in older patients and virus A pdm09 in younger patients with mean age of cases 66.9 and 46.8 years and those with death as outcome 78.8 and 60.2 years, respectively .", "Title: The patient voice: a survey of worries and anxieties during health system transition in HIV services in Vietnam\nPassage: Since October 2007, 1820 patients had registered for the Hanoi cohort, and 1348 were still enrolled and underwent follow-up in October and November 2018. All patients agreed to participate in the survey . Table 1 shows the respondents' characteristics. In all, 58.3% of participants were males. The median age was 40 years. Furthermore, 22.9% of participants had a history of IDU, and nearly 90% had been receiving HIV services at NHTD for 5 years or longer. Approximately one-third lived in provinces far from Hanoi . Title: Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study", "Passage: This is a retrospective study conducted at the ICU of the National Institute of Infectious Disease at Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Our institution has provided care to HIV-positive patients since 1986. There are currently over 3.300 HIVpositive adult under active follow-up at Outpatient Clinic. Cohort characteristics have been published elsewhere . We admit approximately 60-70 patients with HIV-related disease per year in the ICU. Title: Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study\nPassage: The nadir CD4 cell counts lower than 50 cells/mm 3 was independently associated with six-month mortality , p = 0.004), while recent HIV diagnosis was protective , p = 0.01) . We observed a lower six-month survival in patients with nadir CD4 cell counts lower than 50 cells/mm 3 . Title: Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study", "Passage: The main differences between survivors and nonsurvivors for six-month mortality were: nadir CD4 cell count, median time length between HIV-infection diagnoses and ICU admission, SOFA score, and neurological dysfunction. Twenty-one patients had a recent HIV diagnosis . The most recent median CD4 cell count was 36 cells/mm 3 in survivors ; with a median time between CD4 cell count and ICU admission -0.5 months .", "Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: R\u00e9union Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean . The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance , based on the surveillance system of mainland France . Influenza activity generally increases during austral winter, corresponding to summer in Europe . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Despite the distance of 9,300 km between R\u00e9union and France, the island is directly connected to Europe with four daily flights to France. These exchanges can impact respiratory pathogens circulation in southern and northern hemisphere. Results of this study can therefore be of interest to both Indian Ocean and Europe countries. Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: Reunion Island is a French overseas department located in the southwestern Indian Ocean, 700 km east of Madagascar and 200 km southwest of Mauritius. The first imported case of pH1N1/2009v was identified on 5 th July 2009 in a traveller returning from Australia. The first case indicating community transmission was detected on 21 st July . pH1N1/2009v became the predominant circulating influenza virus within four weeks of its first detection, its activity peaked during week 35 and ended at week 38 . Contrary to initial fears, the health care system was not overwhelmed, as morbidity and mortality rates were lower Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: the population of Reunion Island and a Chi2 test was used to analyse differences in age, sex and geographic location. Cumulative incidence rates of infection and seroconversion rates were standardized according to the age structure of the community source).", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: The spotting concentration of the capture antibodies varied from 0.2 to 0.0125 mg/ml . The efficacy of the spotting concentration of the capture antibodies was evaluated by virus culture detection, the proper spotting concentration was determined by a combination of minimized cross reaction and higher signal intensity. Figure 1 illustrates the array layout and Figure 2 demonstrates the result of the three spotting buffers and spot concentration of antibody 2B5 by TBE virus culture detection. Cross reaction detection was also conducted by applying JEV, YF, and DV cultures. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Spot morphology observation demonstrated that spotting buffer containing PBS with 20% glycerol produced tailed spot morphology; buffers containing PBS alone and PBS with 20% glycerol +0.004% Triton-X100 gave good spot morphology . Buffers containing PBS with 20% glycerol and PBS with 20% glycerol+0.004% Triton-X100 produced higher signal intensities than PBS alone. Thus, PBS with 20% glycerol+0.004% Triton-X100 was adopted as the optimized spotting buffer for subsequent experiments. Simultaneously, the spot concentration evaluation suggested that 0.05 mg/ml was optimal. At this concentration, the signal intensity was higher and the cross-reaction did not appear . Consequently, spotting concentration optimization of other capture Title: Linear Quantitative Profiling Method Fast Monitors Alkaloids of Sophora Flavescens That Was Verified by Tri-Marker Analyses", "Passage: b LOD: limit of detection c LOQ: limit of quantitation curves were established by plotting the peak area versus the injected mass of the standard marker compounds. Acceptable linearity was demonstrated for the three marker compounds in the concentration range suitable for sample analysis as shown in Table 2 . System repeatability was evaluated by the peak area of the three marker compounds following consecutive injections of the mixed standard solution. The relative standard deviation was found not to exceed 0.62, 1.15 and 1.10% for MT, OMT and SPR, respectively. The accuracy of the HPLC method was determined by recovery Title: Linear Quantitative Profiling Method Fast Monitors Alkaloids of Sophora Flavescens That Was Verified by Tri-Marker Analyses", "Passage: MT peak was selected as the reference standard, we can calculate the relative weight correction factor SPR/MT as Table 2 ) of trimarker. By taking those two factors into Eqs 1 and 2 respectively, we can get the changes for r and b within 1.2% that certainly can be ignored.", "Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity\nPassage: Text: The 2019 novel coronavirus , originally outbreaking from Wuhan China, has transmitted in an extremely short period to 25 countries and infected over 31 000 individuals as of Feb 06, 2020, causing an international alarm. Basic scientific research has achieved significantly in the investigation of viral origination , transmission and evolution , and unprecedented public health control actions in China have been activated and effectively prevented the otherwise dramatic spread. The 2019-nCoV virus seems more infectious in its public transmission capacity compared to the well-known 2003 SARS virus in spite of the unavailability of convincingly scientific evidence. The mechanism Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity\nPassage: Date: 2020-02-26 Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity\nPassage: DOI: 10.1080/22221751.2020.1732837", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: Koch recognized as early as 1891 that associating the presence of a certain agent with a certain disease is complex, and he therefore postulated guidelines that should be followed before an agent can be classified as a pathogen . His postulates can be summarized in three points: The microbe occurs in every case of the disease in question and under circumstances which can account for the pathological changes and clinical course of the disease; the microbe occurs in no other disease as a fortuitous and nonpathogenic parasite; and , after being fully isolated from the body and repeatedly grown in Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond", "Passage: been made to adjust the Koch's postulates specifically for viruses and the current methodologies deployed , fulfilling these postulates is still not feasible on most occasions due to the lack of an efficient cell culture system, difficulties in antigen synthesis and high levels of viral genetic diversity within viral groups, reviewed in the literature . Title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus\nPassage: for the new disease syndrome were unsuccessful, leading to the disease being temporarily designated mystery swine disease in North America. Koch's postulates for MSD were fulfilled in 1991 with a previously unidentified RNA virus discovered in Europe, named Lelystad virus . The discovery was quickly followed by isolation of the virus, initially referred to as swine infertility and respiratory syndrome virus or SIRS virus, in North America . Title: The social benefits of private infectious disease-risk mitigation", "Passage: The first two axioms imply that P is a matrix of conditional probabilities, and the third implies that it is symmetric.", "Title: Influenza activity in Europe during eight seasons (1999\u20132007): an evaluation of the indicators used to measure activity and an assessment of the timing, length and course of peak activity (spread) across Europe\nPassage: It is not surprising that there was a close relationship between the clinical and virological sentinel data. This relationship should be close, because the diagnosis of ILI or ARI and the subsequent collection of respiratory specimens is done by the same person . Sampling of specimens is also usually at its highest during the period of increased influenza activity, which will lead to increased numbers of positive specimens. Some of the non-matches of sentinel data occurred during the Christmas/New Year period when the clinical and virological surveillance systems are affected by holidays. Title: A systematic review of studies on forecasting the dynamics of influenza outbreaks", "Passage: peak time. Furthermore, during the 2012-2013 influenza season, estimates of influenza activity provided by Google Flu Trends did not match estimates provided by traditional influenza surveillance systems. 32 The challenge therefore remains for timely estimates of influenza activity for weekly forecasts at different geographical levels. Title: Worldwide transmission and seasonal variation of pandemic influenza A(H1N1)2009 virus activity during the 2009\u20132010 pandemic", "Passage: epicenter of a pandemic should consider using this time to implement early interventions that may help further delay the spread of pandemic viruses, as recommended by WHO. 16 Countries in temperate climates might need to plan for the highest levels of activity during the autumn-winter ; this is supported by findings from previous pandemics in countries like the United States., where peaks of activity occurred during the autumn/winter months. 6, 7, 17 Countries in tropical climates can expect influenza activity to be spread out over a longer period of time, with no evident pattern in the timing of their peak Title: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends", "Passage: Most of the influential observations occurred during the peak 2003-04 influenza season. This season was characterized by early and intense influenza activity, a large number of influenzaassociated pediatric deaths, and increased media attention to influenza . It is possible that during this influenza season, physician laboratory testing patterns or patient health care seeking behavior differentially affected the relationship between ILI rates and laboratory confirmation of influenza. Additionally, internet search behavior about respiratory infections during this period could have been different than during subsequent, more typical influenza seasons. These findings are relevant to the applicability of surveillance using internet key word", "Title: The Viruses of Wild Pigeon Droppings\nPassage: The mesivirus 59 UTR contained a highly conserved, 20 nucleotides long motif and apical ''8''-like structure 407 GGAGGTGGTGCTGAAATATTGCAAGCCACT 437 that were also seen in avian origin picornaviruses, including turkey hepatitis virus , duck hepatitis A virus-1 , quail picornavirus and pigeon picornavirus B . All these picornaviruses had type IV-like IRES , however, we could not draw the potential secondary structure of mesivirus IRES. The hypothetical cleavage map of the polyproteins of mesiviruses were derived from alignments with other known picornaviruses and NetPicoRNA prediction . Mesiviruses did not have a putative L protein preceding the capsid region. The P1 regions Title: Viral Interference and Persistence in Mosquito-Borne Flaviviruses", "Passage: through cellular and viral proteases into three structural and seven nonstructural proteins. The ORF is flanked at the 5 and 3 ends by two untranslated regions that are important in viral translation and replication . The virions are spherical and approximately 50 nm in diameter. The capsid protein interacts with the viral genome to form the nucleocapsid, which is surrounded by a lipid bilayer containing the membrane and envelope proteins . Title: Structural Proteomics of Herpesviruses", "Passage: As already mentioned, herpesvirus particles are composed of four morphologically recognized structures: the core, the capsid, a dense surrounding layer of proteins , and finally, the envelope composed of a host-derived membrane containing the viral genome encoded glycoproteins. A major goal of virus structural proteomics is to accurately define the composition of these different structures. The capsid composition can be analyzed using a nuclear capsid purification strategy . During virion production, capsid assembly starts through the interaction of the scaffolding protein and a major capsid protein forming the procapsid . After proteolysis of the scaffolding protein, the small capsid protein Title: Detection of a Fourth Orbivirus Non-Structural Protein", "Passage: The icosahedral orbivirus core-particle is constructed as two concentric protein shells, the sub-core layer which contain 120 copies/particle of the T2 protein , and the coresurface layer composed of 780 copies/particle of the T13 protein . VP1, VP4 and VP6 are minor enzymatic proteins that are packaged along with the ten genome segments within the central space of the virus core . The orbivirus outer-capsid layer is composed of two additional structural proteins , which mediate cell-attachment and penetration during initiation of infection. These outer-capsid proteins are more variable than the core proteins and most of the non-structural proteins, and", "Title: A Global Champion for Health\u2014WHO\u2019s Next?\nPassage: Instead of electing a new Director-General, Lorenz Von Seidlein of Mahidol University, Thailand, argued that \"the problems. . .are now so deeply ingrained that replacing the WHO with new, more appropriate organizations is the logical solution. . .at a fraction of current cost, free of cumbersome, archaic obligations and entitlements and an ability to respond to new problems.\" This viewpoint is indicative of the strength of feeling that WHO's deficiencies have come to evoke in some of those committed to the cause of improving the health of people in low-income and middle-income countries. But this perception acknowledges that an accountable Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: global body will always be needed to promote, set standards in, and evaluate progress toward better health for people in all countries. The next Director-General will need to heed critics of the organization and craft a process of streamlining and restructuring to produce a new WHO that is demonstrably effective in leading responses to threats to health, and efficient in doing so. As Gostin commented to PLOS Medicine, \"WHO urgently needs a bold reform agenda to fix long-standing problems recognized by every independent group that has evaluated the Organization.\" Political machinations and the enemy within, bureaucracy, are likely to impede Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: reform. For example, WHO's regional and country offices are seen by some as unaccountable, yet the agency of the future will need to be connected and responsive to the resources and needs of all constituent countries. As Gostin also noted, \" has failed to include civil society in its governance, unlike. . .newer organizations.\" Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: and focused organizations will be pragmatic. Large-scale infectious disease outbreaks are continuing, and noncommunicable diseases, including cancer, dementia, and mental illnesses, are growing in prevalence and increasing demand for treatment and care. The resources and ingenuity of researchers and clinicians will need to be harnessed, and interventions adapted to new settings, with much greater dynamism. The secular issues of population ageing, conflict, climate change, migration, and others will produce health problems that only an organization with a global reach, responsible to all, can hope to meet. We look forward to welcoming a new leader for WHO with the energy and", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Several national guidelines from high-income countries, as well as the WHO recommendations for low-and middleincome countries, recommend that chest radiography should not be routinely performed in children with ambulatory pneumonia . Indications for chest radiography include hospitalization, severe hypoxemia or respiratory distress, failed initial antibiotic therapy, or suspicion for other diseases or complications. However, point-of-care lung ultrasound is emerging as a promising modality for diagnosing childhood pneumonia . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Chest radiologic changes have been considered the gold standard for defining a pneumonia event because clinical findings can be subjective and clinical definitions of pneumonia can be nonspecific. In 2005, to aid in defining outcomes of pneumococcal vaccine studies, the World Health Organization's standardized chest radiograph description defined a group of children who were considered most likely to have pneumococcal pneumonia . The term \"end-point consolidation\" was described as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung. \"Other infiltrate\" included linear and patchy densities, peribronchial thickening, minor patchy infiltrates that Title: Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008", "Passage: A chest radiograph was performed in 17 and was abnormal in 16 patients. Reported radiological diagnoses were pneumonia , ARDS , pneumothorax , pleural effusion , mediastinal emphysema , pericardial effusion , and severe pulmonary haemorrhage . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The WHO radiologic case definition was not intended to distinguish bacterial from viral etiology but rather to define a sub-set of pneumonia cases in which pneumococcal infection was considered more likely and to provide a set of standardized definitions through which researchers could achieve broad agreement in reporting chest radiographs. However, despite widespread field utilization, there are concerns regarding inter-observer repeatability. There has been good consensus for the description of lobar consolidation but significant disagreement on the description of patchy and perihilar infiltrates . In addition, many children with clinically severe lung disease do not have primary end-point pneumonia: in", "Title: Development of a tool to assess oral health-related quality of life in patients hospitalised in critical care\nPassage: \u2022 Severity the sum of ordinal responses \u2022 Prevalence the percentage of participants answering one or more item with ordinal values 3 or 4. \u2022 Extent the number of items per subject answered with ordinal values 3 or 4 Title: Economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories", "Passage: The need for an unambiguous, extended definition of severity has been noted in the World Health Organization report on the handling of the 2009 pandemic , which highlights the impact pandemic severity has on health care provision and associated costs. In the absence of such definitions, an extended severity metric is presented. This extends the case fatality ratio severity scale devised by the CDC , with hospitalisation and intensive care unit data collected in Australia during the 2009 pandemic. These data have been used to generate a more extensive notion of pandemic severity, relating actual age-specific attack rates with agespecific Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Another important consideration for future clinical trials is the assessment of treatment effect based on predictions of exacerbation frequency and intensity. In other words, the collection of data such as the rate of onset and resolution of an exacerbation from longitudinal studies could be used to determine probabilities of second, third, fourth, etc., exacerbation events in individual patients . The alteration of such probabilities with an experimental treatment could be a more sensitive and reliable approach for assessing treatment effect in clinical trials than recording daily changes in symptoms or medical management. Title: Development of a tool to assess oral health-related quality of life in patients hospitalised in critical care\nPassage: We also assessed three summary variables: severity, prevalence and extent; in a similar fashion to that defined by Slade and co-workers and modified to suit the characteristics of our questionnaire:", "Title: Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides\nPassage: Text: Flavonoids are a class of plant secondary metabolites, which are chemically characterized by a 15-carbon backbone that consists of two phenyl rings and a heterocyclic ring. To date, over 10,000 flavonoids have been characterized from various plants, which are classified according to their chemical structure, i.e., the number and presence of hydroxyl groups and further functional group modifications into various subgroups, such as anthoxanthins, flavanones, and flavanonols . Title: Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides", "Passage: In recent years flavonoids have garnered much attention from various application domains because of the various beneficial effects on human health that have been attributed to them, such as anticancer and antioxidant to anti-inflammatory , antimicrobial and antiviral effects. As final step in their biosynthesis, flavonoids are often glycosylated which has a profound effect on their solubility, stability and bio-activity . For example, the best studied flavonol quercetin, which makes up to 75 % of our daily flavonoid intake, predominantly occurs as different glycosides. Over 350 different quercetin glycoforms have been reported to date with varying pharmacological properties . In Title: Isolation and characterization of a multifunctional flavonoid glycosyltransferase from Ornithogalum caudatum with glycosidase activity", "Passage: C-3\u2032 and C-4\u2032 hydroxyl groups of flavonoids, but not attack the hydroxyl group at C-5 position, consistent with the catalytic behavior towards chrysin . The catalytic results of OcUGT1 towards genistein and daidzein further attested the catalytic preference of C-4\u2032 and C-7 positions. Under the action of OcUGT1, both genistein and daidzein were glycosylated to yield a 4\u2032-monoglucoside and a 7-monoglucoside, respectively . Title: Isolation and characterization of a multifunctional flavonoid glycosyltransferase from Ornithogalum caudatum with glycosidase activity\nPassage: NMR, as described previously 23, 37, 40, 42 .", "Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: The data was further analysed with regard to the age distribution of virus infection . In infants up to 3 months old, RSV was by far the most common pathogen , followed by rhinovirus and PIV3 with 8.1% each. The incidence of RSV, however, decreases significantly with increasing age dropping to 13% in children older than 3 years old, while the reverse relationship is observed for Influenza A and B and HAdV. Rhinoviruses, HBoV and enteroviruses are most frequently observed in children from 4 months to 3 years of age. The age dependency of the virus incidence is visualized in Title: Development of a Symptom Score for Clinical Studies to Identify Children With a Documented Viral Upper Respiratory Tract Infection", "Passage: T he common cold is a ubiquitous feature of childhood. The average child develops up to 6 -8 colds per year, each lasting 7-9 d . Cold symptoms are an extraordinarily common reason for health care utilization in pediatric patients . Beginning in the 1950s, investigators discovered rhinovirus and other viruses that cause the common cold . Subsequently, the term \"viral upper respiratory tract infection\" has become virtually synonymous with \"cold\" for describing the illness. Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial\nPassage: 11-month age group and lowest in the >60month age group . Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: Passive surveillance was conducted from the day of first vaccination; parents were instructed to contact the study center within 24 hours after the child became ill. Active surveillance via scripted telephone contact was conducted from 2 weeks after first vaccination, and contact was made every 1-2 weeks through day 385. ILI was defined as fever by any route and at least 1 of the following: new/worsening cough, sore throat, nasal congestion, or rhinorrhea.", "Title: IL-1\u03b2, IL-6, and RANTES as Biomarkers of Chikungunya Severity\nPassage: CHIKF is an acute illness with abrupt fever, skin rash, arthralgia, and occasional involvement of the nervous system, heart and liver. Prolonged incapacitating arthralgia has sometimes been reported to persist for years . It is of concern that the re-emerged CHIKV has caused considerable morbidity and some fatalities, whereas previously CHIKF was considered as relatively benign. Despite the fact that the clinical features of recent acute CHIKV infections from several countries have been described , little is known about the long-term sequelae or the pathogenesis of arthropathy, and the acquisition of protective immunity remains unexplored. It has been proposed that Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: A study by Ng et al. showed biomarkers indicative of severe CHIKV infection . They found decreased levels of RANTES and increased levels of Interleukin-6 and Interleukin-1b that could be sued for CHIKV detection in patients as indicators of CHIKV-driven cytokine storm. Couderc et al. demonstrate another cytokine, type-I IFN, as a key player in the progression to CHIKV infection . Using an IFN-a/b null mouse model, they demonstrated evidence of muscles, joints, and skin as privileged CHIKV targets, which is consistent with human pathology. Although Ng et al. concluded that RANTES levels were significantly suppressed in severe CHIKF patients Title: IL-1\u03b2, IL-6, and RANTES as Biomarkers of Chikungunya Severity", "Passage: Chikungunya virus , which causes CHIKF, is an alphavirus of the Togaviridae family, with a 12,000-nucleotides linear, positive-sense, single-stranded RNA genome containing two large open reading frames . The first, ORF1, encodes 4 non-structural proteins while ORF2 encodes structural proteins that include 1 capsid protein , 2 major envelope surface glycoproteins and 2 small proteins . CHIKV is transmitted by Aedes mosquitoes . Title: Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity", "Passage: For detection of CHIKV antigens in primary human cells , staining was done as described previously using a commercially available anti-alphavirus mAb 37, 47 . For whole blood and human MDMs, CHIKV infection was directly quantified by the detection of Zs-Green signal under the FITC channel. For detection of CHIKV antigen in RAW264.7 cells, staining was performed with rabbit anti-CHIKV nsP2 antibodies followed by secondary staining with Alexa Fluor 488-conjugated Goat anti-rabbit IgG . For primary human cells, an additional staining step was performed. Surface markers Pacific-Blue-conjugated mouse anti-human CD45, Qdot-605-conjugated mouse anti-human CD19, PerCP Cy5.5 mouse anti-human CD14 and", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: Therefore, the BHRP model was simplified as RP model and is shown as follows: Title: Testing Modeling Assumptions in the West Africa Ebola Outbreak\nPassage: What Makes the Data Collapse? In the SI model, 100% of individuals are eventually infected, therefore, to find agreement with data, our model has to assume a small proportion of individuals in each division are susceptible to the disease. This seems implausible; more likely, all individuals are susceptible and, as they become aware of an infection, they reduce their interactions or otherwise reduce the overall disease transmissibility. To demonstrate this hypothesis, we created a more realistic, although still simplistic, disease model, in which susceptible individuals can become infected , but then recover or are removed 17 . In our data, Title: A Lattice Model for Influenza Spreading", "Passage: The simplifications adopted in the transmission model are numerous. First, we do not consider the time of exposure to the infection. Therefore, short episodes of contacts are on the same footing as long standing contacts. This simplification is quite reasonable for viral diseases, as influenza, for which even short contacts can be sufficient for the transmission process. For other kind of infections, as the bacterial ones, the time of exposure is relevant for the transmission and thus one should properly include it in the model. Moreover, in the present study, the infectivity of the individuals is assumed to be constant Title: Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning\nPassage: reducing the apparent attack rate. The proportion immune within a particular population determines the effective reproductive number by the relationship:", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity . Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: stem loop. Bat SARS-related CoV ZC45 did not have the SARS-COV SL6-like stem loop. Instead, it possessed two other stem loops in this region. All three strains had similar SL7 and SL8. The bat SARS-like CoV ZC45 also had an additional stem loop between SL7 and SL8. Overall, the 5 \u2032 -UTR of 2019-nCoV was more similar to that of SARS-CoV than the bat SARS-related CoV ZC 45. The biological relevance and effects of virulence of the 5 \u2032 -UTR structures should be investigated further. The 2019-nCoV had various 3 \u2032 -UTR structures, including BSL, S1, S2, S3, S4, L1,", "Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters\nPassage: Challenge with hantavirus. Female Syrian hamsters 6 to 8 weeks of age were anesthetized by inhalation of vaporized isoflurane using an IMPAC 6 veterinary anesthesia machine. For i.m. challenges, anesthetized hamsters were injected with 80 PFU ) of virus diluted in phosphate-buffered saline delivered with a 1-ml syringe with a 25-gauge, fiveeighths-inch needle. For i.n. challenges, anesthetized hamsters were administered 50 l delivered as 25 l per naris with a plastic pipette tip . Groups of 8 hamsters were typically used for experimental treatments, unless otherwise stated. All work involving hamsters was performed in an animal biosafety level 4 laboratory. Title: Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters", "Passage: Five-week-old Syrian golden hamsters were infected intranasally with 10 6 PFU/animal of virus or placebo medium in 100 uL. Four days post infection, the nasal turbinates and lungs were harvested from 4 animals per group, homogenized and titered by plaque assay in Vero cells. On day 28 post infection, immunized hamsters were challenged with an intranasal dose of 10 6 PFU/animal of wthMPV/NL/1/00. Four days post-challenge, the nasal turbinates and lungs were harvested and assayed for challenge virus replication by plaque assay. Title: Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters\nPassage: by collecting blood 4 weeks after infection of 8-10 week old ferrets with 6.0 log 10 wthMPV/NL/1/00 administered intranasally. Title: Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host", "Passage: Thereafter, we inoculated litters of 3 and 7-day old NIH-Swiss mice intracerebrally with either 100 or 400 PFU of sSBV, SBVDNSs, SBVp32 or cell culture media as a control . All mice inoculated with sSBV died within 7 days post-inoculation, with the exception of the litter of 7-day old mice inoculated with 100 PFU where 100% mortality was reached at day 9 postinoculation . All control mice were healthy until the end of the experiment. SBVDNSs showed an attenuated phenotype. There was a clear delay in the time of death in the groups inoculated with SBVDNSs and 40-60% of the", "Title: Viral vector-based influenza vaccines\nPassage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adenovirus vectors are attractive as vaccine vectors because their genome is very stable and there are a variety of recombinant systems available which can accommodate up to 10 kb of recombinant genetic material . Adenovirus is a non-enveloped virus which is relatively stable and can be formulated for long-term storage at 4 \u00b0C, or even storage up to six months at room temperature . Adenovirus vaccines can be grown to high titers, exceeding 10 1\u00b0 plaque forming units per mL when cultured on 293 or PER.C6 cells , and the virus can be purified by simple methods . Adenovirus vaccines Title: HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach", "Passage: Adenoviral vectors have been used for a variety of vaccine applications including cancer and infectious diseases . Ad vectors have been utilized as vaccine vectors because of several attributes. This broad utility profile has derived from several key attributes: the viral genome is readily manipulated allowing derivation of recombinant viruses; replication-defective Ads can be derived and propagated easily in complementing cell lines making production of large scale vaccines feasible; Ads infect a broad range of target cells ; they possess a large gene delivery payload of up to 8kb; and the vector can achieve unparalleled levels of in vivo gene Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: both CD4 + and CD8 + T cell responses . The adenovirus vector is another of the most widely evaluated vectors to date to express heterologous antigens, due to ease of production, safety profile, genetic stability, the ease of DNA genome manipulation, and the ability to stimulate both innate and adaptive immune responses and induce both T and B cell responses . They have been extensively examined as a delivery vector in several preclinical and clinical studies for infectious diseases such as anthrax, hepatitis B, human immunodeficiency virus -1, influenza, measles, severe acute respiratory syndrome , malaria and tuberculosis M.", "Title: Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies\nPassage: addition, our more recent understanding of the complex integrated pro-and anti-inflammatory responses to injury has also led to the acknowledgement of a protracted form of immune dysregulation, termed persistent inflammation-immunosuppression and catabolism syndrome . Title: Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the \"bad guy\"?", "Passage: Based on the delicate balance between protection and harm, the posttraumatic inflammatory response has been rightfully termed a \"double-edged sword\" . The present review will outline the current understanding of complement activation and regulation after major trauma, with a focus on specific injury patterns, including musculoskeletal trauma, ischemia/reperfusion, chest and brain injuries. We will furthermore discuss potential new pharmacological strategies related to the targeted inhibition of complement, which may shed some hope into the design of new immunomodulatory treatment modalities for severely injured patients in the future. Title: Role of Antioxidants and Natural Products in Inflammation", "Passage: Inflammation is a vital response of human immune system. Nevertheless, the state of chronic inflammation can have several secondary consequences in biological response associated with enhanced risk of chronic diseases and disorders. Chronic inflammation in tissue usually happens when inflammatory responses are in the absence of an actual stimulus. It usually occurs through infections that are not resolved either within endogenous protection mechanisms or via some other resistance mechanism from host defences . They can also happen from physical or chemical agents, which cannot be broken down, as well as from some kind of genetic susceptibility. Persistence of foreign bodies, Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders", "Passage: Thus it is apparent that obesity and inflammation play major role in the development of T2DM and its associated complications and therefore therapeutic regimens may be targeted towards ameliorating these effects. The control of obesity is recommended in the MedlinePlus 159 site also.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: and August 2013 may have been triggered by an index case becoming infected through DC contact . Sequencing MERS-CoV genomes from the 2013 Al-Ahsa hospital outbreak indicated that multiple viral variants contributed to the cases but that most were similar enough to each other to be consistent with human-tohuman transmission. Molecular epidemiology has revealed otherwise hidden links in transmission chains encompassing a period of up to five months . However, most outbreaks have not continued for longer than two to three months and so opportunities for the virus to adapt further to humans through co-infection and sustained serial passage have Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The first known MERS human-to-human transmission event was one characterized by acute LRT disease in a healthcare setting in Jordan. In stark contrast, a sero-survey of HCW who were sometimes in close and prolonged contact with the first, fatal MERS-CoV case in 2012 , found none of the HCW had seroconverted four months later, despite an absence of eye protection and variable compliance with required PPE standards .", "Title: Estimating the number of infections and the impact of non-\nPassage: lag in observing the effect of interventions on deaths since there is a 2-3-week period between Title: Estimating the number of infections and the impact of non-\nPassage: occurred several weeks prior, allowing for the time lag between infection and death. Title: Estimating the number of infections and the impact of non-\nPassage: lag between infections and deaths, continued rises in daily deaths are to be expected for some time. Title: Estimating the number of infections and the impact of non-\nPassage: Given the lag of 2-3 weeks between when transmission changes occur and when their impact can be", "Title: Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia\nPassage: Annual immunization is the most important preventive measure . However, two classes of antiviral drugs are available and play an important role in the treatment and prevention of influenza : the neuraminidase inhibitors , oseltamivir and zanamivir, which are active against both influenza A and B viruses; and the M2 inhibitors, amantadine and rimantadine, which are active against all influenza A strains, but have no activity against influenza B viruses. In general, the duration for therapy with an NI is 5 days, and with the M2 inhibitors is three to 5 days. Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Treatment of severe influenza presents multiple challenges. The mainstay of therapy for patients with influenza is initiation of antiviral medication as soon as possible after illness onset . Currently available FDAapproved antiviral medications include neuraminidase inhibitors ; cap-dependent endonuclease inhibitor ; and adamantanes . NAIs and baloxavir have activity against both influenza A and B viruses. Adamantanes only have activity against influenza A viruses and are not recommended for treatment of influenza due to widespread resistance among currently circulating strains of seasonal influenza A viruses. Notably, FDA-approved antiviral medications for treatment of influenza are approved for early treatment of uncomplicated Title: Travellers and influenza: risks and prevention", "Passage: Another potential preventive strategy for influenza is the use of antivirals either prophylactically or for early treatment. Currently, the most effective anti-influenza drugs are the neuraminidase inhibitors . 49 M2 inhibitors are rarely used since they suffer from rapid development of virus resistance and virtually all currently circulating seasonal influenza A viruses have pre-existing resistance. 50 Furthermore, M2 inhibitors do have considerable side effects and are not effective against influenza B viruses. Although influenza viruses can develop resistance to individual NIs quite rapidly, the risk of resistance development to the whole class of drugs is unlikely and lower than with Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Data on optimal dosing and duration of therapy with neuraminidase inhibitors are limited in critically ill influenza patients. Enterically administered oseltamivir is the preferred treatment for most hospitalized patients, given the lack of data for intravenous peramivir in this population. The use of inhaled zanamivir is not recommended in in critically ill patients due to the lack of data in hospitalized patients and the risk of bronchospasm in patients with underlying lung disease. Studies indicate that oseltamivir administered orally or via oro/naso-gastric tube is well absorbed in critically ill patients and reaches plasma levels comparable to those in ambulatory patients", "Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers\nPassage: Text: The virus family Arenaviridae consists of only one genus, but most viruses within this genus can be divided into two different groups: the Old World arenaviruses and the New World arenaviruses . The differences between the two groups have been established through the use of serological assays. Most of the arenaviruses cause persistent infection in rodents without any symptoms, and humans acquire a variety of diseases when zoonotically infected. Lymphocytic choriomeningitis virus is the only arenavirus to exhibit a worldwide distribution, and causes illnesses such as meningitis . Congenital LCMV infections have also been reported . Most importantly, viral Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: Abstract: The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World and New World complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: other Old World arenaviruses . Similarly, rabbit anti-sera generated against JUNV-NP show cross-reactivity to the LASV-rNP and LCMV-rNP, although the reaction is weak. However, rabbit anti-sera against LASV-NP and LCMV-NP show a negative reaction to the JUNV-rNP , indicating that rabbit antibodies against JUNV NP might cross-react with the Old World arenavirus NP, whereas antibodies against Old World arenavirus NPs may not be able to react with pathogenic New World arenavirus NPs. Title: Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors", "Passage: The focus of this article is on the OW and NW mammarenaviruses. Phylogenetically, changes in the viral polymerase of the mammarenaviruses may be more associated with older adaptive events dating to the speciation of NW arenaviruses , while more current adaptation, at least with the OW Lassa virus , appears to more prominently associate with the viral surface glycoproteins . This observation is recapitulated when comparing the genetic similarity of the four arenaviral proteins . The arenaviral polymerases have less homology between OW and NW viruses as well as among OW and NW strains compared to the other 3 arenaviral", "Title: Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets\nPassage: Another reason these probes are important in our understanding of Ub chain binding to DUBs, is that DUBs containing S2, S1, and S1 0 sites could potentially bind diUb modules in any of these sites. When looking at a single type of probe, either targeting S1-S2 or S1-S1 0 , this may obscure the results; for example, non-productive binding of a diUb to S1-S2 may inhibit the cleavage of diUb in the S1-S1 0 site. For OTUD2 and OTUD3, it is likely that the S1-S2 sites are the main determinants for polyUb binding and cleavage. We observed that reaction rates Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: The M2 antibody results are shown in Figure 3 . Using 3 units as the threshold of positivity as defined by others , 60 of 136 donors were positive on SWM2 at baseline, and 92 of 136 were positive on HM2. For SWM2, the median level in positive donors was 6.3 units for age <40 and 10.6 units for age \u226540 . Regarding cross-reactivity of individual sera on HM2 and SWM2, approximately half recognized both forms. Of the rest, more donors recognized only HM2, and a few recognized only SWM2. Title: Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets", "Passage: two linked Ub modules can covalently trap DUBs that bind Ub in an S1-S1 0 -directed fashion . Although Ub -based active site-directed probes and activity reagents have proven excellent tools to both identify and characterize DUB activity and specificity for S1-S1 0 cleavage, reagents designed to study S1-S2 site binding and cleavage at the proximal end of a diUb module have been lacking so far. Although it is currently not known whether DUBs can specifically recognize multiple Ub elements to cleave a chain off a substrate at the proximal end, for some human and viral DUBs a specific S2 Title: Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets", "Passage: the OTUD2 OTU constructs process the substrate much more efficiently than the S1 and S2 mutant OTUD2 OTU constructs, whereas the C160A construct does not show any activity at all . These results clearly show that our diUb reagents target the S1 and S2 sites on OTUD2. Likely, OTUD2 utilizes all available Ub-binding pockets to increase specificity for K11-and K33linked polyUb chains.", "Title: Year in review 2012: Critical Care - respiratory infections\nPassage: pathogen isolated in both study groups, but there was a higher prevalence of MDR pathogens in patients with risk factors compared with those without . Of all the risk factors, hospitalization in the preceding 90 days 1.90 to 12.4, P = 0.001) and residency in a nursing home were independent predictors of infection with a resistant pathogen and mortality, emphasizing the fi nding that not all of the studied risk factors contributed equally to the risk of infection by MDR pathogens. Th e authors developed a clinical prediction score for determining the risk of MDR, using four variables . A Title: What we can do? The risk factors for multi-drug resistant infection in pediatric intensive care unit (PICU): a case-control study", "Passage: The cases were reviewed in the microbiology and inspection laboratory database by searching for at least 2 positive cultures. And the medical records of the cases were obtained from the medical record archives. The demographics-related information, regarding clinical care, microbiologic data, treatments provided, and outcomes of the patients with were reviewed and collected. Main contents including the name, gender, age, the length of ICU stays, infection site, operation, invasive operation, antibiotic use, and drug sensitivity were collected. All the data were analyzed after double-entry check. Title: What we can do? The risk factors for multi-drug resistant infection in pediatric intensive care unit (PICU): a case-control study\nPassage: as being statistically significant. Title: What we can do? The risk factors for multi-drug resistant infection in pediatric intensive care unit (PICU): a case-control study", "Passage: It must be mentioned that the findings of our study should be interpreted with the consideration of potential limitations. Firstly, it should be acknowledged that, due to the innate limitations of retrospective studies, a significant proportion of the children had more than one incidence of infection, but only one incidence per patient was analyzed. Secondly, there is ample room for improvement in the explanation of the rationale to include cases, and specially, for the justification of choosing a case: control ratio of 1:1, when the customary ratio is to have at least 2 controls for each case. The relatively limited", "Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: e literature shows that MERS-CoV infects males more than females . e casefatality rate of men is higher than that of women . Males with a history of serious medical conditions are highly susceptible to this infection. Moreover, the mean age of infection in adults is 60 years . e mode of transmission is not entirely understood yet ; however, human-to-human and zoonotic sources of transmission have been documented in many studies. Dromedary camels are the major animal source of MERS-CoV transmission to humans. Interhuman transmission of the virus did not occur easily, but it is seen mainly in patients' Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: of infection among males were found to be twice as high as that of females with suspected cases. Title: The impact of sex, gender and pregnancy on 2009 H1N1 disease\nPassage: suggesting that additional factors are contributing to the increased incidence of infection. In contrast, in Asia, the majority of reported H1N1 cases have been male . In China, males : 1.94, 95% CI: 1.07-2.66) also shed the 2009 H1N1 virus in pharyngeal and nasopharyngeal samples for a longer duration than females suggesting that the transmission potential may be higher in males. Other countries reported no male-female differences in the number of cases of 2009 H1N1, but did not analyse the data stratified by both age and sex . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: female, aged 18, presenting in winter will be less likely to be diagnosed than a male, aged 45, presenting in the summer, or, to give another example, a 60-year-old male who is presenting MERS-CoV signs with a negative lab result may need retesting.", "Title: Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa\nPassage: In 2014, West Africa was heavily affected by an epidemic of Zaire Ebola virus that was unprecedented in its magnitude . Earlier epidemics in the east and middle of the African continent were usually confined to a limited area and brought under control within a few months . Similarly, the West African epidemic began in a rural area around Gu\u00e9ck\u00e9dou, Guinea at the end of 2013, but started to deviate from the typical pattern when cases were observed first in Gu\u00e9ck\u00e9dou City and later in the large urban area of capital Conakry. Around the same time the infection spread from Title: Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa", "Passage: the border area around Gu\u00e9ck\u00e9dou into Liberia, followed by Sierra Leone two months later. Their capitals Monrovia and Freetown were infected shortly after these incursions, allowing the virus to spread in highly urbanised populations with limited health care facilities. In July 2014, the WHO recognised the Ebola epidemic as a public health emergency of international concern. While aid programs were being extended and implemented, the epidemic reached its peak in the autumn of 2014, when hundreds of cases were reported weekly. Subsequently, incidence rates started to decline, bringing the epidemic gradually under control. All countries were declared free of Ebola Title: Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa", "Passage: to introductions in Sierra Leone and Liberia by necessity, because the epidemic origin lies in Guinea. Sierra Leone seems to contribute most to cross-border introductions, mainly in Guinea and some in Liberia. On the other hand, the contribution of Liberia to introductions in other countries, is negligible. Title: Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa\nPassage: at some point in 2015, but transmission seems to be ongoing at a low level as evidenced by the sporadic observation of new cases.", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: through routine surveillance, and thus pose a threat to other people. In contrast, we found viral antibodies in near all patients, indicating serology should be considered for 2019-nCoV epidemiology. A possible shift from oral positive during early infection to anal swab positive during late infection can be observed. This observation implied that we cannot discharge a patient purely based on oral swabs negative, who may still shed the virus by oral-fecal route. Above all, we strongly suggest using viral IgM and IgG serological test to confirm an infection, considering the unreliable results from oral swabs detection. Title: Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats", "Passage: , and ebolavirus antisera tested against marburgvirus antigen . A Pearson's Product-Moment Correlation revealed that there was a statistically significant, strong positive correlation between percent filovirus serological cross-reactivity and percent filovirus amino acid identity . Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case", "Passage: The correlation between viral load and quantitative proinflammatory factors profile was analyzed by Pearson's correlation test using Instat software . Differences were considered significant at p,0.05. Figure S1 The distribution of viral load in selected tissue samples. The viral HA gene and b-actin gene copies in tissues were determined by quantified real-time RT-PCR. The ratios between HA and b-actin gene copies which was showed by logarithm presented the viral-load level in different tissue. Found at: doi:10.1371/journal.pone.0013315.s001 Title: Comparative Serological Assays for the Study of H5 and H7 Avian Influenza Viruses", "Passage: As shown by our earlier study, the emergence of an Egypt H5N1 drift variant exhibited significantly decreased crossreactivity by haemagglutination inhibition and microneutralization assays against the Mexican vaccine seed strain . This evidence, together with previous observations, has raised the important question of the mechanism of antigenic drift under vaccine pressure. Additionally, the key role of an active serological postvaccination surveillance for the assessment of vaccine efficacy and evaluation of crossneutralizing capability of the vaccine concurrent with incremental virus escape from neutralizing antibodies is important .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: The phage particle is self-adjuvanting through multiple mechanisms. Host cell wall-derived LPS enhances the virion's immunogenicity, and its removal by polymyxin B chromatography reduces antibody titers against phage coat proteins . The phage's singlestranded DNA genome contains CpG motifs and may also have an adjuvant effect. The antibody response against the phage is entirely dependent on MyD88 signaling and is modulated by stimulation of several Toll-like receptors , indicating that innate immunity plays an important but largely uncharacterized role in the activation of anti-phage adaptive immune responses. Biodistribution studies of the phage after intravenous injection show that it is cleared Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: The phage particle is self-adjuvanting through multiple mechanisms. Host cell wall-derived LPS enhances the virion's immunogenicity, and its removal by polymyxin B chromatography reduces antibody titers against phage coat proteins . The phage's singlestranded DNA genome contains CpG motifs and may also have an adjuvant effect. The antibody response against the phage is entirely dependent on MyD88 signaling and is modulated by stimulation of several Toll-like receptors , indicating that innate immunity plays an important but largely uncharacterized role in the activation of anti-phage adaptive immune responses. Biodistribution studies of the phage after intravenous injection show that it is cleared Title: A self-aggregating peptide: implications for the development of thermostable vaccine candidates", "Passage: On the other hand, an important finding was the adjuvant effect of the PH peptide. Adjuvants are primarily designed to improve the presentation of antigens, increase the immune response, as well as reduce doses . In PH GFP particles a robust immune response was observed without the need for adjuvant. We found antibodies for the antigen and for PH as expected. However, many adjuvants generate immune responses and. Title: A self-aggregating peptide: implications for the development of thermostable vaccine candidates\nPassage: The use of only PH GFP particles without adjuvant achieved the same response as that achieved with aluminum hydroxide . The antibody titers remained high for more than 14 weeks. This finding highlights the adjuvant effect of the PH GFP particles.", "Title: The origins of the great pandemic\nPassage: The 1918 pandemic was caused by an H1N1 virus . Those whose first exposure had been to a putative H3N8 virus that emerged in 1889 were at high risk of death . Crucially, because children born several years prior to a newly emerged IAV strain can experience that virus as their first IAV infections, one should not expect a clean demarcation of increased risk to coincide with the year of emergence of that H3N8 strain. Although the young-adult mortality rate from the 1918 virus has a sharp peak in those born very near 1889, it stretches back to include those Title: 1918 Influenza: the Mother of All Pandemics\nPassage: 1918 pandemic to produce an attenuated H1N1 Virus? Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: shown that an H3 subtype influenza virus may have been responsible for the 1889 influenza pandemic, which circulated until the emergence of the 1918 pandemic virus, leaving those individuals who had not been exposed to an H1 subtype virus highly susceptible to the pandemic virus . It has also been suggested that the generation of an excessive inflammatory response in healthy, young adults infected with the 1918 virus may have contributed to the excess mortality seen within this age group . Recent in vivo studies with the 1918 virus have shown a marked upregulation of inflammatory cytokines, along with the Title: 1918 Influenza: the Mother of All Pandemics\nPassage: with the previously circulating human H1N1 strain.", "Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically: Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: Significance and potential impact of the study To provide greater insight into social network structures in resource poor settings, we propose to study social contact patterns within schools and households and compare and contrast patterns in the urban and rural setting exhibiting different demographic, economic, and socio-cultural characteristics. This will provide key data for use in transmission dynamic models for common respiratory viral and bacterial infections such as RSV and S. pneumoniae that are the leading cause of childhood morbidity and mortality in the SSA setting. We also seek to answer the question how we can optimize study design to Title: Protocol for development of a risk assessment tool for planning and management of religious mass-gathering events of India\u2014a health system-strengthening initiative", "Passage: A community-based cross-sectional study will be conducted to achieve the last objective of the research study. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: Parents who attend the engagement sessions at the school will be refunded travel expenses. We anticipate that this will not exceed USD 2 . Participating households will also benefit from health talks that focus on prevention of communicable diseases such as pneumonia and diarrhoea. This will include talks on importance of washings hands , use of handkerchiefs or disposable tissues when sneezing or coughing, and a demonstration of proper hand washing techniques. Each household will then receive two bars of hand-washing soap at the end of data collection.", "Title: Vaccines for the future: learning from human immunology\nPassage: Although the RV144 trial has shown the benefit of a primeboost strategy for a preventive vaccine against HIV, it is still not clear which are the effector mechanisms elicited by the vaccine that protected some of the subjects from HIV infection. For difficult intracellular pathogens such as HIV and HCV, protection probably arises from the integration of different effector mechanisms of the appropriate quality. Therefore, correlates of protection are not easily measured by simple antibody or T cell assays, but require more complex readouts. With the progress of genomics it is possible to generate a lot of high-throughput data from Title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?", "Passage: readily measured also play key roles in protection . It is likely that the mechanism of protection and protective level of a particular immune component may well differ in an experimental model in NHPs, challenged in a manner that may not accurately reflect natural exposure and in humans exposed to natural infection. This highlights the importance of not being over-reliant on immunological correlates derived from pre-clinical testing. Clearly, different vaccine delivery methods induce qualitatively different immune responses; induction of long-lasting humoral immunity in the absence of T cells seems unlikely, so the ability of prime-boost regimens to induce durable CMI Title: Clinical vaccine development", "Passage: example . These kinds of vaccines brought dramatic improvement in vaccine safety, mitigating the risk of using purified inactivated antigens obtained from infected patients. Title: A Novel Vaccine against Crimean-Congo Haemorrhagic Fever Protects 100% of Animals against Lethal Challenge in a Mouse Model\nPassage: Most clinical CCHF immunity studies have examined serum antibody levels against the nucleoprotein . Patients with a fatal outcome have a weak or absent antibody response, and Ozturk et al found significant differences between IgM and IgG levels in fatal vs. non-fatal cases . However, other studies were unable to find a significant relationship between the presence of IgM and IgG antibodies and clinical outcome, but found that viral load was a better predictor of prognosis . Virus titres decreased in survivors during the first week of disease, independently of antibodies, suggesting a critical role of innate or cellular immune", "Title: Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population\nPassage: apply to the general population in case of a pandemic. It is possible that the discomfort in wearing associated with a certain type of masks will lead to reduced adherence and thus to a loss in overall protectiveness . Indeed a review among health care workers could not determine whether personal respirators conferred better protection for the health care workers than surgical masks . Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: infection control policies directed that gloves, gowns, goggles, and masks be used when caring for these patients. Use of N95 masks was initially recommended in all hospitals, although hospital 1 changed to surgical masks after June 16, 2009 . Hand hygiene with an alcohol-based product and respiratory etiquette were promoted at all hospitals. Title: Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population", "Passage: With a potential influenza pandemic looming, governments need to decide how they can best use available resources to protect their people against severe illness and death, and to mitigate health and social effects for society as a whole. Much research is being devoted to develop optimal strategies for the use of pandemic vaccines and of anti-virals. There are only limited data to assess the potential effectiveness of non-pharmaceutical interventions to reduce the risk of transmission, including the effect of different kinds of face-masks worn by the general public or by patients. Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: At the individual level, surgical face masks have often been a particularly visible image from affected cities in China. Face masks are essential components of personal protective equipment in healthcare settings, and should be recommended for ill persons in the community or for those who care for ill persons. However, there is now a shortage of supply of masks in China and elsewhere, and debates are ongoing about their protective value for uninfected persons in the general community.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: The complete genome sequence of 2019-nCoV HKU-SZ-005b was available at GenBank . The representative complete genomes of other related \u03b2CoVs strains collected from human or mammals were included for comparative analysis. These included strains collected from human, bats, and Himalayan palm civet between 2003 and 2018, with one 229E coronavirus strain as the outgroup. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Abstract: A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe", "Title: Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines\nPassage: bias of the T cell responses they elicit, resulting in a qualitatively different Tfh response . Title: Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults", "Passage: CD4 and CD8 T cell responses to H1 were assessed by intracellular cytokine staining for IL-2, TNF-\u03b1 and IFN-\u03b3, and by IFN\u03b3 ELISpot as previously described . Vaccine-induced T cell responses were detected by ELISpot, using a commercially available ELISpot Kit . Results were expressed as mean spot-forming cells per million PBMC. A response was considered to be positive if it met the following criteria: the number of spots per 1x10 6 cells minus the background exceeded 100 SFC/10 6 PBMC, and the non-background corrected mean was at least four fold greater than the mean negative stimulation for the sample. Title: Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines", "Passage: interest to replicate our experiments using adoptively transferred transgenic T cells. Nonetheless, clear responses were detectable under most conditions using our assays. Title: Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines\nPassage: Total Tfh responses to the viral vector platforms were greater than those to the protein-in-adjuvant vaccines . For all platforms, the proportion of total Tfh cells, which detectably bound MHC-II tetramers was typically ,5%; nonetheless, Agspecific Tfh responses were clearly detectable above background levels. OVA-specific Tfh responses were significantly higher in adenovirus-vaccinated mice than in other groups . This difference was no longer apparent at day 10, consistent with findings from our kinetic analysis suggesting that at this time point, when the Tfh response in protein/adjuvant immunized mice reached its peak, the response in adenovirus-immunized mice had begun to decline", "Title: Progression of the Radiologic Severity Index predicts mortality in patients with parainfluenza virus-associated lower respiratory infections\nPassage: The use of mortality as a primary endpoint in clinical trials of antimicrobials has been hotly debated due to difficulty in the determination of attribution . The FDA recommended in 2009 that investigators consider clinical response or failure as an endpoint in trials of pneumonia . Radiologic progression is considered a component of clinical failure . However, while some studies of pneumonia have found that radiologic progression or delayed radiologic resolution may be associated with adverse outcomes , other studies have failed to demonstrate this relationship . In other words, equipoise exists as to whether radiologic progression is clinically meaningful. Title: Progression of the Radiologic Severity Index predicts mortality in patients with parainfluenza virus-associated lower respiratory infections", "Passage: Systematic quantification of radiological severity could allow for a valid and reliable score that can serve as a biomarker of mortality. While thoracic computed tomography and chest X-ray are important clinical tools for evaluating pneumonia , few studies have sought to quantify pneumonia severity radiologically . Precise, quantitative imagebased assessments of pneumonia may add prognostic value to existing clinical risk assessment tools , and changes in radiologic severity may predict adverse outcomes after pneumonia . The development of a validated quantitative assessment of radiological severity would allow investigators to measure pneumonia progression or resolution with greater precision and reliability than Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Widespread use of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination has decreased the incidence of radiologic pneumonia. In a review of four randomized controlled trials and two case-control studies of Haemophilus influenzae type B conjugate vaccination in high-burden communities, the vaccination was associated with an 18% decrease in radiologic pneumonia . Introduction of pneumococcal conjugate vaccination was associated with a 26% decrease in radiologic pneumonia in California between 1995 and 1998 . In vaccine efficacy trials in low-and middle-income countries, pneumococcal conjugate vaccination reduced radiologic pneumonia by 37% in the Gambia , 25% in South Africa and Title: New aspects in the management of pneumonia", "Passage: Meijvis et al. 2011 Bicenter RCT in Netherlands Reduction in length of stay in dexamethasone group compared with the placebo group Dexamethasone versus placebo Patients with CAP Chen et al. 2011 Meta-analysis Accelerated the resolution of symptoms or time to clinical stability and decreased the rate of relapse of the disease Patients with pneumonia Nie et al. 2012 Meta-analysis Corticosteroids did not significantly reduce mortality in the general population . The protective effect of corticosteroids on radiographic progression could be interpreted as an effect preventing the development of ARDS or blocking the Jarisch-Herxheimer-like reaction . No significant difference was observed", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Spike glycoprotein comprised of S1 and S2 subunits. The S1 subunit contains a signal peptide, followed by an N-terminal domain and receptor-binding domain , while the S2 subunit contains conserved fusion peptide , heptad repeat 1 and 2, transmembrane domain , and cytoplasmic domain . We found that the S2 subunit of 2019-nCoV is highly conserved and shares 99% identity with those of the two bat SARS-like CoVs and human SARS-CoV . Thus the broad spectrum antiviral peptides against S2 would be an important preventive and treatment modality for testing in animal models before clinical trials . Though the S1 Title: Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels", "Passage: the structure of SARS virus S2 protein 34 as a search probe . Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Here, we developed sM2 consensus derived from the analysis of sequences of H5N1, H1N1 and H9N2 subtypes in the database. Considering the previous findings that extracellular domain particularly is highly conserved among the influenza virus subtypes and recognized as epitope for the induction of monoclonal antibodies, which could protect influenza virus infection , sM2 backbone sequence from the H5N1 virus were used. For the possible homology among other subtypes we changed at the position of 14 and 18 and kept unchanged the conserved epitope . As shown in sequence alignment, sM2 of consensus sequence has 0-8 mismatches among the subtypes Title: Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice", "Passage: Here, we developed sM2 consensus derived from the analysis of sequences of H5N1, H1N1 and H9N2 subtypes in the database. Considering the previous findings that extracellular domain particularly is highly conserved among the influenza virus subtypes and recognized as epitope for the induction of monoclonal antibodies, which could protect influenza virus infection , sM2 backbone sequence from the H5N1 virus were used. For the possible homology among other subtypes we changed at the position of 14 and 18 and kept unchanged the conserved epitope . As shown in sequence alignment, sM2 of consensus sequence has 0-8 mismatches among the subtypes", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: may be safely targeted via host-oriented therapies to impose devastating informational and fitness barriers on escape mutant selection. Furthermore, since MMHPs are often conserved targets within and between virus families, MMHP-targeting therapies may exhibit both robust and broadspectrum antiviral efficacy. Achieving this through drug repurposing will break the vicious cycle of escalating therapeutic development costs and trivial escape mutant selection, both quickly and in multiple places. I also discuss alternative posttranslational and RNA-based antiviral approaches, designer vaccines, immunotherapy and the emerging field of neo-virology. 4 I anticipate international efforts in these areas over the coming decade will enable the tapping Title: Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides", "Passage: When we correlate these biophysical analyses with antiviral activity, data suggest that a synergic combined effect of the membranotropic behavior provided by the cholesterol addition and the increase in solubility conferred by PEG addition explains the antiviral pattern found for these compounds. The optimal peptide must have the correct balance between membrane tropism and solubility. Title: Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases", "Passage: In recent years, host cell-directed antivirals have experienced growing recognition as a new concept for the development of advanced generation antivirals with the potential to counteract the challenge of preexisting or rapidly emerging viral resistance . Novel automated genomics and proteomics analyses have greatly advanced our insight into host-pathogen interactions . These studies have underscored the notion that several cellular pathways are exploited for virus replication , supporting the hypothesis that a host-directed antiviral may enjoy an expanded viral target range, rendering it effective for the treatment of several related viral diseases. Title: Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides", "Passage: the kinetic rate constant of all peptides; only the most potent peptides interact well with membranes in the absence of cholesterol in the target membrane . We speculate that the linear membranotropic properties associated with the effective peptides also affect biodistribution and therefore in vivo efficacy, as they may circulate in association with RBCs. We assessed the serum and RBCs from peptide-dosed animals, and found that peptides are present both in the plasma and on the surface of the RBCs . Association with RBCs may be one mechanism whereby the lipid moieties enhance half-life in vivo. Addition of PEG linkers,", "Title: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics\nPassage: Text: Lion fossils trace to the Late Pliocene in Eastern Africa and the Early Pleistocene in Eastern and Southern Africa coincident with the flourishing of grasslands ,2-1.5 million years ago . By Mid Pleistocene , lions occupied Europe and by the Late Pleistocene lions had the greatest intercontinental distribution for a large land mammal , ranging from Africa into Eurasia and the Americas . Lions were extirpated from Europe 2,000 years ago and within the last 150 years from the Middle East and North Africa. Today, there are less than 50,000 free-ranging lions that occur only in sub-Saharan Africa and Title: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics", "Passage: SER-II, and SER-III, suggesting that lions likely colonized West Asia from the East Africa refugia . Such an expansion may have been favored by the start of a warmer and less arid period in Africa 130,000-70,000 years ago . This ''out-of-Africa event'' would have occurred much later than the initial lion expansion through Eurasia based on fossils . It is likely that multiple lion expansions occurred in the Pleistocene, as occurred with humans . Title: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics", "Passage: A second, more recent lion expansion probably occurred at the Pleistocene/Holocene transition, this one from Southern Africa toward East Africa . This is reflected in the mtDNA linage IV, where haplotypes present in Southern lions are basal to those found in the East. Overall, mtDNA population nucleotide diversity decreases from Southern to East Africa , a finding supported by pairwise mismatch analysis . The fixation of mtDNA haplotype H11 in BOT-I suggests that the colonizing lions expanded northwards from the Kalahari Desert, which included bush, woodland and savannah habitats during the climatic fluctuations of the Pleistocene . This expansion would Title: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics", "Passage: Based on patterns of genetic diversity and phylogenetic analysis of lion nDNA/mtDNA and FIV Ple markers, we propose a scenario of a period of refugia/isolation in the Late Pleistocene followed by two major lion expansions across Africa and Asia. The first expansion, supported by the mtDNA NCPA , was a long-distance colonization of mtDNA lineage-III around 118,000 years ago , with subsequent fragmentation of haplotypes H5-H6 into Central and North Africa and haplotypes H7-H8 into West Asia . Support for this initial expansion is also found in nDNA. The ADA haplotype A5 fixed in GIR in also present in KEN,", "Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo\nPassage: Mapping neuronal connectivity in the central nervous system of even simple organisms is a difficult task. Recombinant viruses engineered to trace synaptic connections and express transgenes promise to enable higher-throughput mapping of connections among neurons than other methods, e.g., serial reconstruction from electron micrographs . The Pseudorabies and Rabies viruses have been the best characterized and most utilized circuit tracing viruses to date . RABV was recently modified by Wickersham and colleagues such that it can travel across only one synapse, allowing for a straightforward definition of monosynaptic connections . This strategy permitted the first unambiguous identification of retrogradely connected Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: A particular advantage of retrograde viral tracers is the ability to label CNS neurons projecting to peripheral sites. This has been a powerful application of both RABV and PRV . To test if rVSV could also perform this function, we examined the innervation of the dura surface by neurons of the trigeminal ganglion, a neuronal circuit thought to be involved in migraine headaches . These neurons have axons, but not canonical dendrites, and send projections into the spinal cord and brainstem. Therefore, the only way trigeminal neurons could become labeled from viral application to the dura is through retrograde uptake Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: A particular advantage of retrograde viral tracers is the ability to label CNS neurons projecting to peripheral sites. This has been a powerful application of both RABV and PRV . To test if rVSV could also perform this function, we examined the innervation of the dura surface by neurons of the trigeminal ganglion, a neuronal circuit thought to be involved in migraine headaches . These neurons have axons, but not canonical dendrites, and send projections into the spinal cord and brainstem. Therefore, the only way trigeminal neurons could become labeled from viral application to the dura is through retrograde uptake Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: Text: Mapping neuronal connectivity in the central nervous system of even simple organisms is a difficult task. Recombinant viruses engineered to trace synaptic connections and express transgenes promise to enable higher-throughput mapping of connections among neurons than other methods, e.g., serial reconstruction from electron micrographs . The Pseudorabies and Rabies viruses have been the best characterized and most utilized circuit tracing viruses to date . RABV was recently modified by Wickersham and colleagues such that it can travel across only one synapse, allowing for a straightforward definition of monosynaptic connections . This strategy permitted the first unambiguous identification of retrogradely", "Title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus\nPassage: BRM delivery should be guided by immune system \"compartmentalization\" to ensure they elicit balanced immune responses. Ideally, mucosal delivery deposits BRMs that reduce viral titers at the site of IAV replication; however, systemic delivery of certain BRMs might be required to dampen dysregulated responses. This not only depends on the BRMs used but also on the timing of their administration. Moreover, the duration of treatment with BRMs must be considered because sustained inhibition of certain inflammatory responses can result in an immune status that increases susceptibility to secondary opportunistic infections. Title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus", "Passage: Local microenvironment within a given tissue can dictate the quality and intensity of an immune response. Inhibition or activation of critical signaling pathways expressed in both respiratory tract epithelial and immune cells by BRMs can have opposite and unintended consequences. As discussed above, TRAIL regulates immune cell-mediated apoptosis of infected cells and several studies have shown that blocking TRAIL signaling by genomic deletion or depletion by monoclonal antibody administration can improve infection outcome in IAVinfected mice. Indeed inhibition of TRAIL signaling in alveolar macrophages and other monocytes limits their ability to induce apoptosis in alveolar cells, prevents lung tissue damage Title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus", "Passage: Repurposing of clinically approved drugs could potentially be used as BRMs for the treatment of severe IAV infectious and should be explored . Considering that susceptibility to severe IAV infections is influenced by host genetics and hostspecific immune responses, selection of therapeutic BRMs should be carried out using in vivo model systems that are representative of the immune status spectrum and underlying conditions of high-risk influenza patients . Using these model systems will increase the likelihood of identifying BRMs with clinically relevant antiviral and immunomodulatory potentials. Title: Is the risk of multiple sclerosis related to the \u2018biography\u2019 of the immune system?", "Passage: The temporal sequence of infections, especially initial and early ones, is crucial to the development of patterns of immune reactivity as prior contacts with other antigens may have induced cross-reactive T-helper cells competing with T reg s. As a consequence T reg s normally induced by the second pathogen may be marginalized or even eclipsed. The latter phenomenon, also known as lateral inhibition, has many parallels in biology, particularly in neurology. The locking of an immune response into an eclipsed state seems to involve an active deletion of clones of T-cells occurring as a result of reinfections or reactivations .", "Title: Quantifying the value of surveillance data for improving model predictions of lymphatic filariasis elimination\nPassage: More recently, attention has also focused on the notion that a model essentially represents a conditional proposition, i.e. that running a model in a predictive mode presupposes that the driving forces of the system will remain within the bounds of the model conceptualization or specification . If these driving forces were to change, then it follows that even a model well-calibrated to a given historical dataset will fail. New developments in longitudinal data assimilation can mitigate this problem of potential time variation of parameters via the recursive adjustment of the model by assimilation of data obtained through time . Apart Title: Mapping the drivers of within-host pathogen evolution using massive data sets", "Passage: 1) The model. Overall, the model is well described and mostly well motivated. I do have some modest concerns however. Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: 1) The model. Overall, the model is well described and mostly well motivated. I do have some modest concerns however. Title: Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database\nPassage: to bring a virtuous cycle for the entire system, whereas TBI researchers might obtain more resources for further study.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: It was proposed that the S gene from bat-derived CoV, unlike that from human patients-or civetsderived viruses, was unable to use human ACE2 as a receptor for entry into human cells . Civets were proposed to be an intermediate host of the bat-CoVs, capable of spreading SARS CoV to humans . However, in 2013 several novel bat coronaviruses were isolated from Chinese horseshoe bats and the bat SARS-like or SL-CoV-WIV1 was able to use ACE2 from humans, civets and Chinese horseshoe bats for entry . Combined with evolutionary evidence that the bat ACE2 gene has been positively selected at the Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: The pathogenicity of these viruses is typically species-dependent, as is the severity of infection; they infect mainly their natural hosts and/or species that are closely related. Certain virus infections, however, can cross the species barrier, with the prime example being the zoonotic SARS-CoV, a novel coronavirus that is thought to have originated from bats before it adapted to its intermediate host, civet cats, and finally to humans . Bat colonies, which are scattered worldwide, are widely known to play host to a variety of coronaviral and adenoviral pathogens while acting as natural wildlife reservoirs of these viruses . Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies", "Passage: Bats are the natural reservoirs of both SARS-CoV and MERS-CoV. SARS-CoV crossed the species barrier into palm civets and other animals in live animal markets in China, which then infected human, while a MERS-CoV ancestral virus crossed species barrier into dromedary camels. Abundant circulation of MERS-CoV in camels results in continuous zoonotic transmission of this virus to human, while SARS-CoV was not found to circulate in the intermediate reservoirs, explaining SARS being a one-off outbreak and MERS a continuing zoonotic disease . Aerosolgenerating procedures such as intubation were associated with increased viral transmission of both CoVs resulting in nosocomial outbreaks Title: Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans", "Passage: Bat-borne zoonotic viruses have been responsible for several important emerging zoonotic infectious disease outbreaks in the last two decades including Hendra virus, Nipah virus, Ebola virus, SARS and MERS coronaviruses . It is important to note that, almost in all of the cases, an intermediate host has been identified to play a crucial role in amplifying and transmitting the virus from bats to humans such as horses for Hendra virus, pigs for Nipah virus and palm civets for SARS-CoV . With multiple reports of PRV presence in bats in many parts of Asia and a higher than expected prevalence in", "Title: Current and Novel Approaches in Influenza Management\nPassage: LAIV viruses in the nasopharynx elicit immune response that epitomizes a natural influenza infection. For this reason, LAIV has shown some superiority over the IIV in terms of the induction of mucosal immunity via secreted immunoglobulin A . Use of the LAIV has proven to be safe in children and immunocompromised persons . The most spelt-out advantage is the \"non-invasive\" capacity of the attenuated viruses and this had made it suitable to use for all categories of vaccines, although LAIVs are not recommended for people with underlying chronic medical conditions . A typical setback to the use of the LAIV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: in humans . Currently, NA-specific antibody responses are not considered a correlate of protection . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx . LAIV immunization induces serum antibody responses, mucosal antibody responses , and T cell responses. While robust serum antibody and nasal wash antibody responses are associated with protection from infection, other immune responses, such as Title: Virus-Vectored Influenza Virus Vaccines", "Passage: February and then manufacturers begin production, taking at least six months to produce the millions of vaccine doses required for the fall . If the prediction is imperfect, or if manufacturers have issues with vaccine production, vaccine efficacy or availability can be compromised . LAIV is not recommended for all populations; however, it is generally considered to be as effective as inactivated vaccines and may be more efficacious in children . While LAIV relies on antigenic match and the HA and NA antigens are replaced on the same schedule as the TIV , there is some suggestion that LAIV may Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: Overall, birds in the LAIV-LAIV group showed consistently high mucosal antibody responses across all three ELISA tests . The LAIV-IIV group also showed a good level of antibody response that was somewhat biased toward IgG response despite the fact that the IgA response observed in this group was not significantly different from the LAIV vaccinated groups . The single vaccination regimens administered at 3 weeks of age showed a trend that was similar to the 1-day-old vaccination result: no differences in anti-NP or IgG antibodies and higher IgA responses in LAIV groups compared with IIV groups .", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: access areas for medical personnel and a dressing area for technologists. The clean area Title: Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center\nPassage: in the ICUs group. The overall daily hospital bed occupancy rate was approximately 92% during the study period. In the busy surgical wards, if the surface is not visibly dirty, it may not receive attention or wiping. It is important to simplify the cleaning workflow and strengthen wiping of the hightouch surfaces in a timely manner. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: , semicontaminated , buffer , and clean areas Title: Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center", "Passage: Phase 1 served as a baseline phase, during which there were no additional interventions. At this medical center, routine disinfection of the surfaces in specific areas close to patients, such as bed rails and overbed tables, are disinfected daily in the ICUs and weekly in the general wards. Areas distant from patients, only light switches, door knobs and bathrooms are disinfected daily in all types of wards. The disinfectant is 600 ppm sodium hypochlorite that diluted by the ESWs according to the manufacturer's instructions for routine disinfection and terminal cleaning/ disinfection.", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: The increase in access to early information from diverse sources including media and social media adds an important dimension to identifying and tracking new events globally and is a key part of the overall epidemic intelligence system. However, it is also a potential source of disinformation. When, as has been seen in this outbreak, the volume of information coming in exceeds any capacity to collate and analyse it and to attempt to cross-reference and verify separate items, there is a risk that the information fuels speculation and media and public concern. Again there is a fine balance between information that Title: Incorporating media data into a model of infectious disease transmission", "Passage: Public reaction to common or seasonal diseases can be limited , even though such diseases are often deadly. Using data from the 2014-2015 influenza season in Washington, DC, we explored the role of media in a typical, seasonal outbreak and demonstrated that the low level media interest exhibited during the influenza season was associated with only a small reduction in the number of cases. Media may be a tool for public health officials to communicate preventive measures to the public during disease outbreaks. Therefore, the effect of significantly increasing the volume of media coverage was explored. It was found that Title: The impact of media coverage on the transmission dynamics of human influenza", "Passage: Media simplifications can lead to overconfidence in the idea of a vaccine as a cure-all. The result is not just a vaccinating panic and a blow-out epidemic, but a net increase in the endemic equilibrium. Thus, media coverage of an emerging epidemic can fan the flames of fear and also implicitly reinforce an imperfect solution as the only answer. Title: Crisis Communication in Public Health Emergencies: The Limits of \u2018Legal Control\u2019 and the Risks for Harmful Outcomes in a Digital Age", "Passage: events involving H1N1 influenza, SARS and more recently the Ebola outbreak in West Africa. 26 In each of these instances economic harm was caused because of incorrect information that had been disseminated by various agencies. 27 Unfortunately for those concerned, the harms caused were capable of continuing long after incorrect information had been corrected. This is because of a 'genie out of the bottle effect' whereby once it has been disseminated, false information can not simply be retracted and will likely be further disseminated by private individuals and actors.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: phage populations in tandem with the relative abundance of free-living heterotrophic bacteria . Environmental metagenomics efforts are just beginning to unravel the composition of viral ecosystems. The existing data suggest that filamentous phage comprise minor constituents of viral communities in freshwater and reclaimed and potable water but have much higher frequencies in wastewater and sewage , with the caveat that biases inherent to the methodologies for ascertaining these data have not been not well validated. There are no data describing the population dynamics of filamentous phage and their host species in the natural environment. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: phage populations in tandem with the relative abundance of free-living heterotrophic bacteria . Environmental metagenomics efforts are just beginning to unravel the composition of viral ecosystems. The existing data suggest that filamentous phage comprise minor constituents of viral communities in freshwater and reclaimed and potable water but have much higher frequencies in wastewater and sewage , with the caveat that biases inherent to the methodologies for ascertaining these data have not been not well validated. There are no data describing the population dynamics of filamentous phage and their host species in the natural environment.", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: areas. In these areas, new systematic review literature is needed to inform practice and policy decision making. It is unclear at this time whether gaps pertain only to reviews lacking in these topic areas, or whether there is a corresponding lack of primary studies as well, hindering the production of reviews. In some instances it may be necessary to first develop the primary study base in order for studies to be available for synthesis in a systematic review. Future reviews should be conducted on these broad topic areas for which review-level evidence on the effectiveness of interventions is lacking. Funding Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: There are promising indicators of demand for reviews, including actions being taken to promote the use of reviews , an awareness of sites providing access to review-level evidence and an increasing number of groups generating summaries of reviews . Despite this heightened activity, given the gaps, a greater investment is needed to provide an evidence base that can meet demand and determine how to apply existing good quality systematic reviews in different contexts . Organizations involved in the conduct of systematic reviews should direct synthesis funding to areas lacking in review content, or should consider higher-level reviews of reviews , Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: this lack of review-level evidence doesn't necessarily indicate a lack of evidence . There may be primary research or other forms of evidence that can inform decisions but which may not yet have been synthesized. In cases where there are no eligible studies available to be reviewed for a particular topic, the result can be an \"empty review\", meaning that no studies were located which met the inclusion criteria to answer the question for review. Empty reviews can go unreported but may in fact be useful since empty reviews indicate interest in an area, highlight gaps, and offer a snapshot Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: of the state of research evidence at the time of publication . Even in light of a lack of evidence, or poor reporting of the evidence, decision makers can and should take an informed approach to having insufficient evidence . An informed approach may be needed in topic areas that demonstrated a lack of review-level evidence, such as dental health, environmental health, food safety and inspection, and seniors' health, and particularly for public health priority areas such as healthy communities and social determinants of health. Consequently, the best literature may be sparse or of low quality in these particular topic", "Title: Host genetics determine susceptibility to avian influenza infection and transmission dynamics\nPassage: The ability to sustain a chain of infection of LPAI among resistant Line 0 birds correlates with cloacal shedding and is dependent on viral strain. We compared the profile of viral shedding of directly infected and close-contact sentinel birds with H7N7 and two H9N2 LPAI strains and A/Turkey/Wisconsin/1/66 , Fig. 6 ). H7N7-infected birds showed the characteristic pattern of viral shedding, transmission of infection and serological responses previously described . Title: The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries", "Passage: 2.1.1. Outbreak of H7N1 in Italy in 1999/2000 Northern Italy has experienced a number of avian influenza outbreaks from 1997 onwards . These all occurred in an extremely dense poultry production area and involved a significant number of farms keeping turkeys, a species known from experimental studies to be highly susceptible to avian influenza . Furthermore, in this region there are many wetlands and resting sites for migratory waterfowl in close proximity to the poultry industry, which likely lead to multiple introductions from the wild bird host. Title: Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses", "Passage: high sequence identities of the viruses from the patients and the LPMs further confirmed the linkage between the human infections and LPM exposure. Multiple basic amino acids were present at the cleavage site between HA1 and HA2, which indicated that these viruses were highly pathogenic in chickens . Mutations in HA related to an enhanced human-like receptor binding ability were detected in the human and environmental viruses . The I368V mutation at PB1, which has been reported to be associated with increased transmissibility in ferrets, was detected in the present study. Title: Poultry farms as a source of avian influenza A (H7N9) virus reassortment and human infection\nPassage: patient's poultry farm .", "Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China\nPassage: Shandong province has a population of 94 million. It is a relatively developed province with a per capita GDP 1.6 times of the national average in 2010 . The prevalence rate of TB in Shandong was lower compared with the average rate of China in 2000 . Population representative samples were drawn in Shandong in the surveys of 2000 and 2010 using similar methods. The study aimed to estimate the TB prevalence in Shandong based on the 2010 survey, and compare results of the two cross sectional surveys. Title: Travel Patterns in China", "Passage: By contrast, Guangdong province has a rapidly growing population and is now the largest province by population; it is also the richest province. Shenzhen city is a Special Economic Region, meaning it is more open to trade and commerce than other parts of China. Since it was established in the early 1980s, it has grown to a population officially recorded as 8.6 million at the end of 2007 with an average population density of 4200 people/ km 2 . Shenzhen is a major manufacturing centre in China, but industries also include finance and high-tech enterprises. The population can be divided Title: Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China", "Passage: A stratified multi stage random sampling was used to select the 35 clusters within 17 prefectures in Shandong province. The number of clusters was randomly allocated in proportion to the provincial population at the prefectural, county/district and township levels. A cluster was defined as a community with a population of 1250 to 1750 adults . If the community contained less than 1250 adult residents, the neighboring community to the north was annexed. If the community or combined communities containing more than 1750 adults, we randomly selected households and then included all adults in the household for the survey until the Title: Travel Patterns in China\nPassage: Anhui is a mainly agricultural and relatively poor province. Huangshan city has a population of 1,470,000, comprising both urban and rural areas. The population density overall is 180 people/km 2 .", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Within a year, the E1-A226V mutation was present in La Reunion Island, and Ae. albopictus apparently vectored the large epidemic infecting 34% of La Reunion Island's population . All of the CHIKV strains isolated from Mayotte carried the E1-A226V mutation, and the mutation was also found in Madagascar in 2007 . The E1-A226V mutation was not present at the beginning of the Indian Ocean Islands outbreak . However, more than 90% of later viral strains found there had incorporated the mutation , indicating a genotype switch during the winter season . Title: Influenza A Virus on Oceanic Islands: Host and Viral Diversity in Seabirds in the Western Indian Ocean", "Passage: Of the 227 samples that tested ELISA positive, 156 were further tested for the identification of HA-specific antibodies with the VN or HI assays. The remaining 71 samples could not be tested because of the limited volume of serum available. For the same reason, not all samples were tested for all 16 described IAV HA subtypes. In total, 147 samples were tested for H1-H9, H11-H12 and H14-H15, 103 were tested for H10, and 88 for H13 and H16. Title: Influenza A Virus on Oceanic Islands: Host and Viral Diversity in Seabirds in the Western Indian Ocean\nPassage: the Western Indian Ocean, and this may have resulted in underestimating subtype prevalence. Thirdly, failure to isolate viruses from positive samples precluded the sequencing of the full genomes of the H2 IAVs from Reunion Island, therefore limiting possible inferences on their phylogenetic and geographic origins. Title: Influenza A Virus on Oceanic Islands: Host and Viral Diversity in Seabirds in the Western Indian Ocean\nPassage: positive .", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: SARS to novel coronavirus \u2013 old lessons and new lessons", "Passage: Text: On 29 December 2019 clinicians in a hospital in Wuhan City, China noticed a clustering of cases of unusual pneumonia with an apparent link to a market that sells live fish, poultry and animals to the public. This event was reported to the World Health Organisation on 31 December . Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the", "Title: A bibliometric analysis of IL-35 research from 2009 to 2018\nPassage: further analysis. Title: Estimating the number of infections and the impact of non-\nPassage: main analysis. Title: Dynamic variations in the peripheral blood lymphocyte subgroups of patients with 2009 pandemic H1N1 swine-origin influenza A virus infection\nPassage: Statistical analysis SPSS 13.0 statistical package was used for data processing. Measurement data were indicated as mean \u00b1 standard deviation or percentages. Comparisons among groups were carried out using one-way ANOVA or \u03c7 2 test. Differences with P < 0.05 were considered statistically significant. Correlation analysis among the detection indicators were conducted using Spearman's rank correlation analysis. Title: Dynamics of the Developing Chick Chorioallantoic Membrane Assessed by Stereology, Allometry, Immunohistochemistry and Molecular Analysis", "Passage: Data analysis. Statistical analysis was performed to pick differences among the volumes of CAM as well as the proportions of the various CAM components and their absolute volumes at selected time points. To achieve this, Microsoft Excel 2010 was used to perform single factor ANOVA to detect significant differences. Scheffe's test was used to perform posthoc analysis of the targeted values using Graphad Software free online at: .", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: The pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination have been effective tools to decrease pneumonia incidence, severity and mortality . However, equitable coverage and access to vaccines remains sub-optimal. By the end of 2015, Haemophilus influenzae type B conjugate vaccination had been introduced in 73 countries, with global coverage estimated at 68%. However, inequities are still apparent among regions: in the Americas coverage is estimated at 90%, while in the Western Pacific it is only 25%. By 2015, pneumococcal conjugate vaccination had been introduced into 54 countries, with global coverage of 35% for three doses of pneumococcal Title: Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985\u20132008", "Passage: Better access to proven public health interventions, including vaccines, is needed in the public sector in China. Vaccines against Haemophilus influenzae type b , Streptococcus pneumoniae, and influenza are not part of routine childhood vaccination programs in many countries worldwide ; none of these vaccines are included in the routine childhood immunization schedule in mainland China. However, Hib and influenza vaccines are commonly available in many parts of China through vaccination clinics, and Hong Kong SAR is the first region in China, as well as Asia, where pneumococcal conjugate vaccine will be included in their routine childhood immunization program starting Title: Annual influenza vaccination: coverage and attitudes of primary care staff in Australia", "Passage: coverage than PNs from the Australian Capital Territory . 29 The Australian National Influenza & Pneumococcal Survey provides the earliest available influenza vaccination coverage estimates for GPs in Australia. 16 Results of this survey found coverage for NSW GPs was the lowest of any jurisdiction, with 29% vaccinated in 1998, and just over 20% for the preceding 3 years. Comparing these rates to those observed in our study, influenza vaccination coverage amongst GPs in NSW appears to have risen substantially from 1998 to 2008. Title: A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations", "Passage: as very young children, the elderly and those suffering from chronic lung or heart diseases are at risk for serious influenza complications, e.g. bacterial pneumonia . Influenza reaches peak prevalence in winter in the Northern hemisphere -as well as in the Southern hemisphere and circulates yearround in the tropics . Seasonal influenza vaccination is an effective prevention strategy and is therefore routinely recommended for special risk groups . Of note, the seasonal influenza vaccine recommendations of the U.S. Centres for Disease Control were recently expanded and include now about 80% of the population .", "Title: Antiviral immunity is impaired in COPD patients with frequent exacerbations\nPassage: with positive virus detection. Frequent exacerbators had significantly reduced sputum cell expression of IFN\u2424, IFN2/3, and IFN1 mRNAs at exacerbation presentation . Sputum 2'-5=OAS mRNA expression was also significantly reduced at exacerbation presentation in frequent versus infrequent exacerbators with no differences observed for viperin or Mx1 expression . Frequent exacerbators also had reduced sputum concentrations of the interferon-inducible cytokine CXCL10/IP-10 at exacerbation onset and 2 wk after onset . Title: Host susceptibility to severe influenza A virus infection", "Passage: Susceptible hosts may have impaired intracellular controls of viral replication , defective interferon responses , or defects in cell-mediated immunity with increased baseline levels of systemic inflammation . In the context of any of these susceptibility mechanisms, failure to clear the virus is an expected consequence, indicating that a full course of effective antiviral therapy is likely to benefit this population. In the future, understanding the biological mechanisms of susceptibility to severe IAV may yield therapeutic targets to modify the biology of the susceptible hosts in critical care and render them resilient. Title: Antiviral immunity is impaired in COPD patients with frequent exacerbations", "Passage: corroborate these data with medical records due to the heterogenous nature of locations at which these exacerbations will have been reported and managed , preventing a systematic approach to data retrieval. It is also important to note that a relatively short follow-up period was adopted in this study. Since exacerbations may be influenced by seasonal variation in influenza rates, a longer-term follow-up period may offer more accurate information. This short follow-up in our study makes it unsuitable for testing the hypothesis of whether baseline deficiency in antiviral immunity predisposes to subsequent increased frequency of virusinduced exacerbations. An adequately powered study Title: Antiviral immunity is impaired in COPD patients with frequent exacerbations", "Passage: predispose such patients to greater risk of acquisition of pathogenic viruses and bacteria and/or promote a greater likelihood of developing an exacerbation following an infection. . Patients with COPD also have increased virus loads and enhanced exacerbation severity when experimentally infected with rhinovirus . However, defects in antiviral immunity have not been shown universally with other studies reporting the opposite effect of augmented ex vivo antiviral responses in COPD . The discrepancy between these COPD studies suggests that defective immunity may not be present in all patients with a number of confounding competing factors, such as disease severity and medications", "Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: There were four potential limitations to our study. First, we only conducted a cross-sectional study in Study 3, whereas it would be preferable to measure Chikui likelihood earlier and then track the material and mental benefit of our participants years later. In the absence of a longitudinal study, our findings are suggestive but do not prove causality, and the following two questions therefore remain unaddressed: we are unable to confirm whether the correlation found in Study 2 means that it is the belief that boosts both financial and psychological well-being, rather than the reverse . Only a longitudinal study can Title: Chinese journals: a guide for epidemiologists", "Passage: results. However, subsequent studies found little evidence supporting this assertion. Pham et al. found that language bias led to an under-estimation of the protective effect of intervention in RCTs in complementary and alternative medicine systematic reviews but not in that of conventional medicine . Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: A classic human study found that, in donors lacking neutralizing antibodies, pre-existing cytotoxic T-cell levels against influenza correlated with reduced virus shedding but not reduced symptoms after influenza virus challenge . Epidemiological studies of the 1957 pandemic, an H1N1 to H2N2 shift, suggested cross-protection, but these studies were too small for statistical significance or lacked laboratory confirmation of self-reported symptoms . A human challenge study found a correlation of CD4 memory with reduced illness duration, viral shedding, and symptom severity . Title: Associations of hand-washing frequency with incidence of acute respiratory tract infection and influenza-like illness in adults: a population-based study in Sweden", "Passage: or less confined population segments have yielded a similar overall pattern of results with a mix of positive studies and studies with non-significant effects on the primary outcome but some positive findings in subgroup analyses . Almost unavoidable limitations, including Hawthorne effects and outcome information bias, make the results unpersuasive. Graphs showing crude data of disease occurrence over time in positive studies are unconvincing . Hospital-based case-control studies of SARS and severe influenza, limited by their inherent uncertainty as to the controls' representativity of the population strata that generated the cases, and the possibility of recall bias, provide the most", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: On the other end of the spectrum, viruses that induce strong type 1 inflammation and cell death such as IFV and certain CoV , may not cause prolonged inflammation due to strong induction of antiviral clearance. These infections, however, cause massive damage and cell death to the epithelial barrier, so much so that areas of the epithelium may be completely absent post infection . Factors such as RANTES and CXCL10, which recruit immune cells to induce apoptosis, are strongly induced from IFV infected epithelium . Additionally, necroptotic factors such as RIP3 further compounds the cell deaths in IFV infected epithelium Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: responses, driving chronic airway inflammatory diseases and exacerbations . In addition, Spalluto et al. also showed that antiviral factors such as IFN\u03b3 epigenetically modifies the viral resistance of epithelial cells. Hence, this may indicate that infections such as RV and RSV that weakly induce antiviral responses may result in an altered inflammatory state contributing to further viral persistence and exacerbation of chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Finally, viral infection can result in enhanced production of reactive oxygen species , oxidative stress and mitochondrial dysfunction in the airway epithelium . The airway epithelium of patients with chronic airway inflammatory diseases are usually under a state of constant oxidative stress which sustains the inflammation in the airway . Viral infections of the respiratory epithelium by viruses such as IFV, RV, RSV and HSV may trigger the further production of ROS as an antiviral mechanism Aizawa et al., 2018; Wang et al., 2018) . Moreover, infiltrating cells in response to the infection such as neutrophils will also trigger respiratory Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Another mechanism that viral infections may use to drive acute exacerbations is the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. Infection with a multitude of respiratory viruses causes disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells. For example, IFV infection was found to induce oncostatin M which causes tight junction opening . Similarly, RV and RSV infections usually cause tight junction opening which may also increase the infiltration rate of eosinophils and thus worsening", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: role of the RNA methylation machinery in controlling inflammatory mRNA stability. These activities take place in various subcellular compartments and are differentially regulated during infection. In this way, mRNA-destabilising RBPs constitute a 'brake' on the immune system, which may ultimately be toggled therapeutically. I anticipate continued efforts in this area will lead to new methods of regaining control over inflammation in autoimmunity, selectively enhancing immunity in immunotherapy, and modulating RNA synthesis and virus replication during infection. Title: Identification of RNase L-Dependent, 3\u2032-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells", "Passage: The main protective mechanism against 3=-5= degradation is a 2=-O-methylation on the 3= proximal ribose, which prevents degradation by exoribonucleases and thus helps to stabilize small RNAs such as miRNAs and siRNAs in plants, piRNAs in animals, and siRNAs in Drosophila melanogaster . This suggests that RNA modification could have evolved as a response to protect the anti-pathogen small RNAs during infections. Posttranscriptional RNA modifications represent an important but not yet fully understood system to regulate transcripts. Cellular RNAs contain many distinct posttranscriptional modifications at thousands of sites. In the same way, RNA viruses take advantage of nucleoside modifications on Title: Focus on Translation Initiation of the HIV-1 mRNAs", "Passage: HIV-1 infection is associated with an increase of adenosine methylation of both cellular and viral mRNAs that drives opposite effects on viral expression and replication. Lichinchi et al. have characterized 14 distinct sites of methylation found in the 5 UTR, the coding regions, and within the RRE element. The silencing of the two METLL3 and METLL4 writer proteins or the ALKBH5 eraser significantly decreases and increases HIV-1 replication, respectively, indicating that m 6 A modifications are needed. A focus on the impact of m 6 A residues located in the RRE showed that methylation controls the interaction between RRE and Title: The Structure-To-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and Their Contributions to Viral Pathogenesis", "Passage: spectrometry, DNA-seq or RNA-seq; Examples of deep-sequencing based mapping techniques that are used to address the four most common epitranscriptomic modifications in RNA. The N 6 -methyladenosine is detected with individual-nucleotide-resolution cross-linking and immunoprecipitation methodology. Here, immunoprecipitation and UV crosslinking with m 6 A-specific antibodies is coupled with reverse transcription and deep-sequencing, and the sites of modification are detected as either misincorporation of base-pairs or truncation. Pseudouridine is detected by CMC-derivatization, where sodium carbonate removes the CMC derivative from non-pseudouridine modifications. The 5-methylcytosine uses bisulfite conversion that causes non-methylated cytosines to be converted to guanine. The N 1 -methyladenosine ,", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: of movement restriction that was in place from 5 February onwards. Figure 1 shows the epidemic curve by contact history and type of membership. The highest incidence of illness onset was observed on 7 February. The epidemic curve in a latter half period was dominated by crew members whose movement was not strictly controlled due to the need to continue service on the ship. The second dominating group was passengers with close contact history. The last illness onset date on board of a passenger without close contact was on 14 February. Estimating the incidence of infection, the peak incidence was Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Abstract: To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus . The epidemic curve of a total of 199 confirmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Text: An outbreak of novel coronavirus disease has occurred on a cruise ship, the Diamond Princess . The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a", "Title: Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers\u2019 Understanding to Improve Health Care\nPassage: Our study suggests that junior healthcare workers should also be focused and educational program must be designed to target this group to increase their knowledge about JE. Title: Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers\u2019 Understanding to Improve Health Care", "Passage: A self-administered questionnaire was designed and used as an instrument to collect data from the participants. A thorough literature review was done initially by two of the authors and relevant research papers were shortlisted for further discussions among authors . After all the selected papers were comprehensively reviewed by the authors, an initial draft of the questionnaire was designed. The questionnaire was then subjected to content validity and face validity. The draft was sent to 3 pharmacy and medical academicians responsible for delivering lectures relating to infectious diseases for their opinion on the contents of the questionnaire. The suggestions given Title: Assessing dengue control in Tokyo, 2014\nPassage: 2014. Title: Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers\u2019 Understanding to Improve Health Care", "Passage: The strength of this study is that it has explored an area where not much research has been done. Additionally, this study would help the stakeholders in India to design customized interventions to optimize the knowledge and attitudes of HCWs towards JE. However, this study also has some limitations like any other study. The results should be interpreted with cautions as the convenience sampling approach utilized in this single centre study may not be generalizable to the whole state or country. Additionally, we cannot ignore the tendency of participants to provide more socially desirable responses. However, despite of these limitations,", "Title: Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines\nPassage: Abstract: Inovirus-associated vectors are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or Title: Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines", "Passage: The easy genetic manipulation of inoviruses and the possibility of inserting random oligonucleotides into their genome set the foundation for inovirus display technology . Expression of these genetically modified inoviruses results in the presentation of oligopeptides as fusion proteins on the surface of the virion and are herein termed IAVs for inovirus-associated vectors. IAVs can be modified to express an oligopeptide on either all or on some copies of a particular capsid protein. One possibility is to insert an oligonucleotide sequence of interest in the viral genome to create a fusion with capsid protein gp3, gp7, gp8 or gp9, so Title: Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines", "Passage: vaccinated mice could neutralize five out of ten pseudoviruses from a panel . All the above experiments clearly show that the inoviruses are capable of inducing a specific cellular immune response: the ability of the inoviral vectors to induce both arms of adaptive immunity is unique and it could prove to be valuable in the development of a successful HIV-1 vaccine. Title: Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines\nPassage: spots on the surface of a frequently mutating virus such as HIV-1 and therefore, their identification and further study could lead to new drug therapies or vaccine targets. This review focuses particularly on the applications of inovirus display technology that utilizes capsid proteins gp3 and gp8, as those have been used in vaccine development.", "Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort\nPassage: Chest radiograph appearances were recorded as lobar consolidation in 43.7%, patchy localised consolidation in 25.0% and diffuse, bilateral changes in 29.3%. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Chest radiologic changes have been considered the gold standard for defining a pneumonia event because clinical findings can be subjective and clinical definitions of pneumonia can be nonspecific. In 2005, to aid in defining outcomes of pneumococcal vaccine studies, the World Health Organization's standardized chest radiograph description defined a group of children who were considered most likely to have pneumococcal pneumonia . The term \"end-point consolidation\" was described as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung. \"Other infiltrate\" included linear and patchy densities, peribronchial thickening, minor patchy infiltrates that Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Several national guidelines from high-income countries, as well as the WHO recommendations for low-and middleincome countries, recommend that chest radiography should not be routinely performed in children with ambulatory pneumonia . Indications for chest radiography include hospitalization, severe hypoxemia or respiratory distress, failed initial antibiotic therapy, or suspicion for other diseases or complications. However, point-of-care lung ultrasound is emerging as a promising modality for diagnosing childhood pneumonia . Title: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan\nPassage: Pulmonary infiltrates were seen on chest X-ray in 127 patients. Thoracic CT-scan excluded a CAP diagnosis in 16.5 % of these 127 patients; on the contrary, thoracic CT-scan revealed a parenchymal infiltrate in 27 % of the 73 patients without infiltrate on chest X-ray.", "Title: Tracking social contact networks with online respondent-driven detection: who recruits whom?\nPassage: past 12 months . Less than half of all seeds reported at least one symptom, while more than half of the recruits reported symptoms. Of all participants, 8.3 % self-reported they had influenza of which 32.3 % had received the influenza vaccine, resulting in an OR of 0.64 0.42-0.95] for self-reported influenza by vaccinated individuals . Title: Detecting a Surprisingly Low Transmission Distance in the Early Phase of the 2009 Influenza Pandemic", "Passage: Although schools remained closed during summer , they had a major role in the spread of infection. In particular, considering the whole pandemic, we estimated that 17.8% of the infections are linked to contacts at school -this is remarkable considering that the fraction of school-age individuals in England corresponds to only 20% of the population. Moreover, we estimated that 34.7% of infections occurred in households, and 47.5% in 'other settings' . Title: Rapid detection of pandemic influenza in the presence of seasonal influenza", "Passage: case, about 25% and a slightly lower than 50% detection levels were achieved by the WCR method within the first 4 and 5 weeks while the Mov-Avg Cusum and the threshold methods still trailed below the 25% detection level. The same trend was observed when, for the fixed specificity of 99%, the case reporting rate \u03b1 was raised from 0.5% to 1% to 5% . At the elevated reporting rates, decrease in specificity further increases the detection level for all methods. But the increase in pandemic detection within the first few weeks of pandemic is more pronounced for our method Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: population; we would know who was infected and who was not , with high confidence. The reporting rate is the ratio of reported cases over the number of seropositive individuals. It was statistically evident that increasing in reporting was likely, and thus it should be considered in the future investigation of this outbreak.", "Title: A systematic review of barriers to data sharing in public health\nPassage: purposes such as outbreak detection. Data preservation or archiving is often not prioritized, especially in situations of limited capacity and resources . Even if data have been preserved, data retrieval systems may be lacking. This is amplified by relocation of offices, staff turnover, physical damage to paper or electronic files, computer viruses, computer theft, etc. . 4. Language barrier. Routinely collected public health data are often recorded in local languages, limiting the possibility to integrate and use such data together with other data sets, particularly in an international context . 5. Restrictive data format. Despite major advances in computational resources Title: A systematic review of barriers to data sharing in public health", "Passage: These barriers for the most part are well understood as part of resilient challenges in health information system capacity and continue to form a major obstacle to the availability and use of public health data. Solutions to these barriers have been identified but sustainable implementation and political/financial commitment have been limited. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: the high cost of a doctor's appointment was definitely a deterrent to seeking treatment. The issue of trust is illustrated by this extract from a woman who believes she was misdiagnosed in the emergency department putting vulnerable family members at risk. Title: A systematic review of barriers to data sharing in public health", "Passage: We identified 20 unique real or potential barriers to data sharing in public health and classified these in a taxonomy of six categories: technical, motivational, economic, political, legal, and ethical barriers . These barriers and categories describe a landscape of challenges that is highly dynamic, interconnected, and hierarchical. Although most evidence was published in peer-reviewed sources, less than a quarter of all the documents reviewed was based on empirically derived evidence, indicating that a large volume of published expert knowledge has not yet been translated into scientific evidence.", "Title: Travellers and influenza: risks and prevention\nPassage: to the onset of symptoms. 48 Title: Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China\nPassage: According to the clinical data, the initial symptoms of A infection were primary fever, coughing, and fatigue. These findings are consistent with those of other published reports. The atypical symptoms recorded during the early stage of A patients were noteworthy. Two elderly patients were hospitalized due to neurological syndromes. The symptoms of A virus infection were covered up by the neurological syndromes which cause the delay for treatment. Given the high case fatality and features of patients in Guangzhou, it is important to remain on alert for those high risk people. Prior studies have suggested that the time of onset Title: The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS)", "Passage: The most commonly reported symptoms among episodes of disease were respiratory , including coughing, sneezing/runny nose, sore throat and dyspnoea, in decreasing order. Other disease episodes included: fever , headache , body aches , and digestive disorders , including diarrhoea and vomiting/nausea. Title: The Waiting Time for Inter-Country Spread of Pandemic Influenza\nPassage: presentation occurs some time after onset of symptoms and the bulk of infectivity occurs immediately after onset of symptoms the results on the effect of early presentation of cases are likely, in practical terms, to be similar to those found here. Given the variable nature of influenza symptoms, there is likely to be a difference between the onset of the first symptoms as measured in a clinical trial ) and the time that a person in the field first suspects that they may be infected with influenza virus. To fully resolve the issue of how effective very early presentation of", "Title: Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study\nPassage: Sample size determination. We estimated that a sample of at least 500 was required to achieve 80% power at an a = 0.05 to reject a model of the specified complexity if the model fit index Root Mean Square Error of Approximation exceeded 0.08 . To allow for a response rate ,60% in the follow-up and the baseline surveys, we need to target at least 1,389 subjects in the baseline survey. Title: Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh", "Passage: Considering an estimate of 50% knowledge level , with 5% precision of error, 95% confidence interval, and 80% power, the required sample-size was 384 for each arm. Taking into account a design effect of 2 and an estimate of 20% non-response rate, the sample-size was calculated to be 960 in each arm. Therefore, the total sample-size for three arms of the KAP survey was 2,880. Title: Association of Cytokines in Individuals Sensitive and Insensitive to Dust Mites in a Brazilian Population", "Passage: Sample size calculation was based on city demographic data from the 2013 Census, with a population of 386,000 inhabitants. Assuming a 10% margin of error, maximum prevalence of 50% and 95% confidence interval, a minimum sample of 96 participants was required. Considering a possible loss of 10%, the final sample size was estimated at 138 participants . Controls were defined according to the approximate number of cases, totaling 116 participants. Sample size was calculated using Statdisk version 8.4 . Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: to justify this sample size are given below. Given an average household size of 3.8, a study of 200 households will involve the enrolment of a total of 760 individuals .", "Title: Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia\nPassage: Annual immunization is the most important preventive measure . However, two classes of antiviral drugs are available and play an important role in the treatment and prevention of influenza : the neuraminidase inhibitors , oseltamivir and zanamivir, which are active against both influenza A and B viruses; and the M2 inhibitors, amantadine and rimantadine, which are active against all influenza A strains, but have no activity against influenza B viruses. In general, the duration for therapy with an NI is 5 days, and with the M2 inhibitors is three to 5 days. Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Treatment of severe influenza presents multiple challenges. The mainstay of therapy for patients with influenza is initiation of antiviral medication as soon as possible after illness onset . Currently available FDAapproved antiviral medications include neuraminidase inhibitors ; cap-dependent endonuclease inhibitor ; and adamantanes . NAIs and baloxavir have activity against both influenza A and B viruses. Adamantanes only have activity against influenza A viruses and are not recommended for treatment of influenza due to widespread resistance among currently circulating strains of seasonal influenza A viruses. Notably, FDA-approved antiviral medications for treatment of influenza are approved for early treatment of uncomplicated Title: Pharmacotherapy of Lower Respiratory Tract Infections in Elderly\u2014Focused on Antibiotics", "Passage: and serologically confirmed influenza in adults older than 60 years old . For the diagnosed Influenza, neuraminidase inhibitors , including oseltamivir , zanamivir , and peramivir , are effective against both influenza A and influenza B viruses. Title: Using Complementary and Alternative Medicines to Target the Host Response during Severe Influenza\nPassage: vaccines or antivirals.", "Title: Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection\nPassage: The clinical course and outcome of all patients are summarized in Figure 1 . In the analysis of 15 patients who visited the emergency department, the mean interval between symptom onset and emergency room visit was 1.7 days \u00b1 1.5 days . In the analysis of all 18 patients, the mean interval between symptom onset and the start of oseltamivir phosphate administration was 3.9 \u00b1 1.6 days . In addition, the mean interval between symptom onset and symptom improvement was 4.7 \u00b1 1.7 days . Title: Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China", "Passage: The median time from onset of illness to first medical care was 1 day . Time from onset to hospitalization was 4 days , and time from onset to confirmation was 7 days . Here, 24 cases received oseltamivir treatment after a median of 5 days from the onset of symptoms, with 5 patients receiving oseltamivir treatment within 48 h of onset. The 14 patients who died did so at a median of 10 days after onset. According to the Mann-Whitney test, there was no significant difference between the fatal and nonfatal groups with respect to time elapsed from onset Title: A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections", "Passage: 'Time from symptom onset' was defined as the duration from the appearance of the first presenting symptom till the time of blood sample collection. The distribution of 'time from symptom onset' in our cohort peaked at 2-4 days after the initiation of symptoms with substantial proportions of patients turning to medical assistance either sooner or later . Figure S7 . Distribution of time from initiation of symptoms . N/A -healthy controls or patients for which data was not obtained. Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies", "Passage: HIV infection. Median time from the onset of symptoms to enrollment was five days for patients enrolled in the general ward and 10 days for patients enrolled from an ICU. Eighteen patients developed ILI symptoms after being hospitalized for some other condition; the median time between admission and ILI symptom onset As would be expected, by most measures of disease severity assessed patients enrolled in the ICU had more severe illness than those enrolled from the general ward. Exceptions were a history of asthma/chronic obstructive pulmonary disease , cardiovascular disease , liver or renal disease, and exacerbations of other co-morbidities", "Title: A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs\nPassage: the necessity of having a picture as detailed as possible of molecules expressed by each cell type to understand its interactive network in a tissue. both coding and non-coding genes have an expression that is cell-to-cell dependent and support the necessity of having a picture as detailed as possible of molecules expressed by each cell type to understand its interactive network in a tissue. . Differences in lncRNA expression between cells at different stages of reprogramming. Some lncRNAs seem to be specifically expressed in the less specialized cells, suggesting that they might be involved with the maintenance of the pluripotency Title: A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs", "Passage: LncRNAs can interact with miRNAs to act as post-transcriptional regulators of protein expression. miRNAs are short non-coding RNAs that interact with target mRNAs for their cleavage or to simply repress their translation . LncRNAs that interact with miRNAs are classified as competing endogenous RNAs . This definition was proposed by Salmena and colleagues in 2011 . ceRNAs are also known as miRNA sponges and compete with mRNAs for miRNA binding . One example of ceRNA is the long intergenic non-coding RNA-Muscle Differentiation 1 . This is a muscle-specific transcript of about 500 nucleotides that contains numerous target sites for miR-133 Title: A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs\nPassage: LncRNAs can also be localized in a genomic region that overlaps protein-coding genes. These transcripts are called genic lncRNAs. Title: A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs", "Passage: the union of the molecules expressed from different cells composing the tissue identifies the 10,000 activated genes that are found using bulk samples. Moreover, most single-cell expression protocols are based on RNA retrotranscription using oligod as primers for the RT enzyme. This means that only RNAs having poly have been retrotranscribed losing information on RNAs without poly such as, for example, mature miRNAs, that are important non-coding RNAs involved in post-transcriptional gene regulation. Adaptor ligations to both 5 and 3 ends while using masking oligonucleotides to eliminate rRNAs may be an alternative method to evaluate the expression of non-polyadenylated RNAs", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: The use of mechanical ventilation and ECMO in patients with ARDS caused by HAdV-55 has not been detailed in previous studies. In our cohort, we found that severe HAdV-55 infection could cause a rapid progression of respiratory failure, with a very high failure rate for NPPV and IMV. This failure rate may be a result of the large area of consolidation that induced a severe shunt in the lung, which may lead to lack of response to positive pressure ventilation. For patients with severe ARDS, ECMO should be considered a better choice for oxygenation. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: The use of mechanical ventilation and ECMO in patients with ARDS caused by HAdV-55 has not been detailed in previous studies. In our cohort, we found that severe HAdV-55 infection could cause a rapid progression of respiratory failure, with a very high failure rate for NPPV and IMV. This failure rate may be a result of the large area of consolidation that induced a severe shunt in the lung, which may lead to lack of response to positive pressure ventilation. For patients with severe ARDS, ECMO should be considered a better choice for oxygenation. Title: A multicenter RCT of noninvasive ventilation in pneumonia-induced early mild acute respiratory distress syndrome", "Passage: Although more than half of mild ARDS cases \u2264 300 mmHg but > 200 mmHg) rapidly evolve to moderate or severe ARDS , many of these patients may not require invasive mechanical ventilation with the lower severity of mild ARDS. Our pilot study suggests that NIV for patients with mild ARDS reduced the need for intubation and the number of organ failures compared with conventional administration of oxygen through a Venturi mask. In this study, NIV also reduced the need for intubation in pneumonia-induced mild ARDS . However, because of the small sample size and the etiological heterogeneity of this Title: Noninvasive positive pressure ventilation for acute respiratory failure in children: a concise review", "Passage: The most challenging application of NPPV may be in patients with ARDS. Studies of NPPV for the treatment of ARDS in adult population have reported failure rates of 50-80% . A meta-analysis of the topic in adult population concluded that NPPV was unlikely to have any significant benefit . In children, the use of NPPV for the treatment of ARDS was associated with a failure rate of 78%, and 22% of them died . Therefore, NPPV use in such a patient group is rarely justified. However, if a trial of NPPV is initiated, patients should be closely monitored and promptly", "Title: Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control\nPassage: Other important considerations involved in setting up public private partnerships include establishing the correct balance between the variety of players that are involved as each may have different and often competing interests. If the correct balance is not initially established or is not continuously maintained, there is a potential to lose focus and the most urgent problems may not be addressed. The PRP has resolved these issues by setting up the organization in a similar manner as the GAELF . The PRP maintains a light governance structure, meeting biannually to discuss global issues regarding rabies prevention and control, identify gaps Title: Identification of MicroRNA-Like RNAs in Mycelial and Yeast Phases of the Thermal Dimorphic Fungus Penicillium marneffei", "Passage: protein. RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules involved in mitosis, while cytochrome P450 catalyses diverse reactions in fungal primary and secondary metabolism, and xenobiotic detoxification. As for PM-milR-M2, 20 potential targets were predicted, which include 13 transposon or transposable elements and seven conserved hypothetical proteins. Title: Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control", "Passage: human and animal public health principles, diagnostics and surveillance, education and advocacy, anthropology, social mobilization and community outreach, research and development, and program implementation and evaluation as well as funding options. The need for such comprehensive strategies has been clearly identified following the successful adoption of this approach in Latin America leading to dramatic impacts on human and animal rabies cases . The PRP was able to draw on global expertise to incorporate all of these aspects into a Blueprint for rabies prevention and control which is currently available online. . As a next step, the PRP is focusing on Title: Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control", "Passage: GARC is the first global nongovernmental organization focusing specifically on increasing awareness and advocacy for rabies prevention and control by supporting communityled interventions. Using the GAELF as an example, the PRP was established in 2008 and is comprised of an informal group of stakeholders working in the field of rabies prevention and control. This is the first time that a working group consisting of all key stakeholders in the field of rabies have joined to find workable solutions to rabies control, including timelines and deliverables. The PRP includes representatives from major international health organizations , Food and Agriculture Organization ,", "Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: HMPV is reported to have an important contribution to acute respiratory infections in Africa. For instance, HMPV-associated hospitalization was estimated at 6.5 per 1000 person years in infants in Soweto, South Africa ; at 4% in hospitalized children with severe ARI during a 2-year period in Cameroon ; and in rural western Kenya, incidence of HMPV associated with ARI cases in outpatient clinic visits was estimated at 0.43 per 100 person-years among outpatients . In Kilifi coastal Kenya, between January 2007 to December 2011, children under 6 months of age accounted for 44% of HMPV positive cases, while 74% were Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: HMPV is reported to have an important contribution to acute respiratory infections in Africa. For instance, HMPV-associated hospitalization was estimated at 6.5 per 1000 person years in infants in Soweto, South Africa ; at 4% in hospitalized children with severe ARI during a 2-year period in Cameroon ; and in rural western Kenya, incidence of HMPV associated with ARI cases in outpatient clinic visits was estimated at 0.43 per 100 person-years among outpatients . In Kilifi coastal Kenya, between January 2007 to December 2011, children under 6 months of age accounted for 44% of HMPV positive cases, while 74% were Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: children under 1 year, and 1.3% were children > 36 months . In Dadaab and Kakuma refugee camps in Kenya, HMPV was detected in 5.7% hospitalizations, and virus-positive crude hospitalization rate was 4 for HMPV . In Mali, contribution of HMPV to pneumonia had a population attributable fraction of 9% ; while in Morocco , 8 .9% of children < 5 years admitted with severe pneumonia were infected with HMPV. HMPV prevalence and incidence elsewhere globally, is indicated in Additional file 4: Table S1 . Of note is that the variations in incidence rates could be attributed to study population, Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: children under 1 year, and 1.3% were children > 36 months . In Dadaab and Kakuma refugee camps in Kenya, HMPV was detected in 5.7% hospitalizations, and virus-positive crude hospitalization rate was 4 for HMPV . In Mali, contribution of HMPV to pneumonia had a population attributable fraction of 9% ; while in Morocco , 8 .9% of children < 5 years admitted with severe pneumonia were infected with HMPV. HMPV prevalence and incidence elsewhere globally, is indicated in Additional file 4: Table S1 . Of note is that the variations in incidence rates could be attributed to study population,", "Title: 3\u2032,8\u2033-Dimerization Enhances the Antioxidant Capacity of Flavonoids: Evidence from Acacetin and Isoginkgetin\nPassage: The superoxide anion radical scavenging activity was determined using the improved pyrogallol autooxidation method . In brief, the sample was dissolved in methanol . The sample solution was mixed with Tris-HCl buffer containing Na 2 EDTA . Pyrogallol was added, and the mixture was thoroughly shaken at room temperature for 3 s. The absorbance of the mixture was measured at 325 nm every 30 s for 5 min. Tris-HCl buffer was applied as a blank. Title: 3\u2032,8\u2033-Dimerization Enhances the Antioxidant Capacity of Flavonoids: Evidence from Acacetin and Isoginkgetin\nPassage: where \u2206A 325nm, control is the increment in the absorbance at 325 nm of the mixture without the sample and \u2206A 325nm, sample is the increment of the mixture with the sample; T = 5 min. Title: 3\u2032,8\u2033-Dimerization Enhances the Antioxidant Capacity of Flavonoids: Evidence from Acacetin and Isoginkgetin", "Passage: To the above ABTS + \u00b7 working solution , the test sample and methanol were added to adjust the total reaction system to 100 \u00b5L. After incubating for 6 min, the absorbance of the 100 \u00b5L mixture was measured at 734 nm by using a microplate reader . The percentage inhibition was calculated based on the formula as follows: Title: 3\u2032,8\u2033-Dimerization Enhances the Antioxidant Capacity of Flavonoids: Evidence from Acacetin and Isoginkgetin", "Passage: The concentration response curves were analyzed using Origin 6.0 professional software . The IC 50 value was defined as the final concentration required for 50% radical inhibition . It was calculated by linear regression analysis and expressed as the mean \u00b1 standard deviation . The linear regression was analyzed using Origin 6.0. The determination of significant differences between the mean IC 50 values was performed by using one-way ANOVA analysis and the t-test. The analysis was performed using SPSS software 13.0 for Windows. p < 0.05 was considered statistically significant.", "Title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling\nPassage: Weekly respiratory virus identifications from September 1999 to August 2006 were obtained from the Respiratory Virus Detection Surveillance System , Public Health Agency of Canada . The RVDSS collects, collates, and reports weekly data from participating laboratories on the number of tests performed and the number of specimens confirmed positive for influenza, respiratory syncytial virus , para-influenza virus , and adenovirus. Specimens are generally submitted to laboratories by clinicians in the course of clinical care, and by clinicians participating in one of our national influenza surveillance programs, ). Indicators of influenza activity are reported year round on a weekly basis Title: Evaluation of Coseasonality of Influenza and Invasive Pneumococcal Disease: Results from Prospective Surveillance", "Passage: A national network of hospital and provincial laboratories submit weekly reports of numbers of tests performed and numbers of positive tests for influenza A and influenza B to the Public Health Agency of Canada. For the purpose of this study, the surveillance data of the province of Ontario from 1 January 1995 through 3 October 2009 were included in the analysis. Title: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends", "Passage: available Google Flu Trends historical ILI estimates and exclude the 2009 H1N1 pandemic which began during the 2008-09 influenza season. Analyses were performed by ''influenza season,'' defined as the period from July 1 through June 30 of the subsequent calendar year. As done in similar analyses , we restricted our analysis to the period during which CDC influenza surveillance is intensified, from calendar week 40 through calendar week 20 of the subsequent year. Title: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends\nPassage: during peak periods of influenza circulation, a substantial number of cases of febrile respiratory illness may have non-influenza etiologies. In the United States, during the spring wave of the 2009 H1N1 outbreak from March through August 2009, the proportion of positive influenza laboratory tests did not exceed 45% .", "Title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia\nPassage: important role in pathogenesis of bacterial infections as bacteria utilize Fe for survival, growth and proliferation; therefore, it is of paramount importance to control the Fe metabolism . It is well known that the abundance of Fe suppresses defense system leading host vulnerable to infections. There is a significant relationship between Hepcidin, Fe metabolism, inflammation, and the immune system. The fact that hepcidin plays an active role in the regulation of Fe release from macrophages and in the control of excessive Fe absorption from the duodenum is well documented . Hepcidin is a part of the natural defense mechanism, thus Title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia", "Passage: Hepcidin is a low molecular weight, antimicrobial peptide hormone and was first discovered in human urine . It is produced by the liver as a firstline response to inflammatory reactions and high Fe concentrations . Hepcidin plays a fundamental role in the regulation of Fe metabolism , which is a part of foundational cellular functions and thus of vital importance. On the other hand, by participating in redox reactions leading to the production of reactive oxygen species , Fe also causes oxidative stress. Therefore, Fe has been regarded as a potentially toxic element to cells . Fe also plays an Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: Hepcidin regulates iron metabolism by binding to ferroportin and causing its internalization and degradation. We therefore investigated the ferroportin levels in both whole lung tissue and alveolar macrophages. As expected, the ferroportin in the control mice was almost totally degraded, whereas a higher ferroportin level was observed in the hepcidin knockdown mice . Title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia", "Passage: by the presence of inflammation in the body, Fe storage, and erythropoietic activity in the bone marrow and plays a primary role in the homeostasis of Fe . The increase in tissue and plasma Fe levels stimulates the synthesis of hepcidin and reduces Fe release and enteric Fe absorption from macrophages and hepatocytes . Increased hepcidin concentrations during inflammation and infection reduce serum Fe levels by decreasing Fe release from macrophages and hepatocytes, and thus Fe required for microorganisms and tumor cells is restricted .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Innate immune mechanisms. The nature of interactions between hantavirus pathogen-associated molecular patterns with the pattern recognition receptors of susceptible endothelial cells are beginning to be clarified. The prototypical HTNV appears to be recognized by TLR-3 . Such an infection has consequences such as increased expression of HLA-DR in dendritic cells and differentiation of monocytes toward dendritic cells . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: be quickly cleared or rendered less competent in its replication so as to blunt any pathological response in the host . The anti-hantavirus innate response can in some cases be attributed to viral interaction as a ligand of TLR-3, but not in others, and in endothelial cells, it appears not to require more than the viral particle itself, even when introduced in replication-incompetent form . Proteins and mRNAs prominently induced by hantaviruses include MxA and IFIT-1 and others including some with known or suspected anti-viral activity. Those hantaviruses, often highly pathogenic strains, that fail to induce a potent antiviral response, Title: The role of viral persistence in flavivirus biology", "Passage: Hantavirus infections are another interesting example of viral persistence. Hantaviruses are segmented, RNA viruses that cause lifelong infections in their reservoir rodent hosts, despite high levels of neutralizing antibodies . Pathogen recognition receptors, such as RIG-I and TLR7, are not elevated in the lungs of infected rats, suggesting that evasion of viral recognition may contribute toward the establishment of a persistent infection. Perhaps, the reason for noninduction of RIG-I is the fact that hantaviruses do not produce detectable amounts of dsRNA . IFNs, such as IFN-b, IFN-k, MxA, and pro-inflammatory chemokines, cytokines, and transcription factor genes are elevated midway in Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters", "Passage: The role that immune cell types may play in disease pathogenesis may not be limited to direct antiviral responses or cytokines. As cells such as neutrophils, monocytes, and lymphocytes are recruited to sites of infection, they undergo the process of transendothelial cell migration, which is highly regulated by integrins, cadherins, and junctional adhesion molecules to prevent vascular leakage during the process . Hantaviruses inactivate and dysregulate beta 3 integrins and VE-cadherin , making it possible that infected endothelial cells may not be able to reform junctional complexes following paracellular diapedesis, leading to vascular leakage. Presumably, this would lead to visible", "Title: Viral vector-based influenza vaccines\nPassage: were capable of inducing protective immunity against infection with homologous viruses in mice. Although recombinant baculovirus vector vaccines were tested in mice, efficacy data in other animal models is still lacking. Short-term production of baculovirus-based influenza virus vaccines for use in clinical trials is therefore not likely. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Baculovirus has been extensively used to produce recombinant proteins. Recently, a baculovirus-derived recombinant HA vaccine was approved for human use and was first available for use in the United States for the 2013-2014 influenza season . Baculoviruses have also been explored as vaccine vectors. Baculoviruses have a number of advantages as vaccine vectors. The viruses have been extensively studied for protein expression and for pesticide use and so are readily manipulated. The vectors can accommodate large gene insertions, show limited cytopathic effect in mammalian cells, and have been shown to infect and express genes of interest in a spectrum of Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Baculovirus vectors have been tested as influenza vaccines, with the first reported vaccine using Autographa californica nuclear polyhedrosis virus expressing the HA of PR8 under control of the CAG promoter . Intramuscular, intranasal, intradermal, and intraperitoneal immunization or mice with AcCAG-HA elicited HA-specific antibody responses, however only intranasal immunization provided protection from lethal challenge. Interestingly, intranasal immunization with the wild type AcNPV also resulted in protection from PR8 challenge. The robust innate immune response to the baculovirus provided non-specific protection from subsequent influenza virus infection . While these studies did not demonstrate specific protection, there were antigen-specific immune responses and Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is growing data on the potential use of baculovirus or pseudotyped baculovirus as a vaccine vector, efficacy data in mammalian animal models other than mice is lacking. There is also no data on the safety in humans, reducing enthusiasm for baculovirus as a vaccine vector for influenza at this time.", "Title: Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift\nPassage: was likely to reflect the various influenza virus strains to which they were exposed to during their life, in children, it seemingly represents \"true\" cross-reactive antibodies. Title: Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift", "Passage: Interestingly, not all antibodies cross-reacted with each other. One possible way to explain this is that in all cases cross-reactive antibodies are generated but we did not detect these in our assays. Regardless of whether this is accurate or not, it is clear that protective cross- reactive antibodies were probably not generated in every individual. It is possible that the genetic background of the individuals dictated whether he will develop crossreactive antibodies. In this regard, it will be interesting to characterize the MHC class I and class II haplotypes of individuals who generated cross-reactive protective antibodies and to compare to Title: Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift", "Passage: antibody cross-reactivity could provide information essential for the design of broadly, cross-reactive vaccine. Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection\nPassage: of particular interest, as this epitope is a promising target for a broadly protective influenza vaccine . Furthermore, the cross-reactive antibodies carried highly mutated immunoglobulin genes, indicative of extensive affinity maturation. Together, these findings support a model in which infection predominantly activated broadly cross-reactive memory B cells that then underwent further affinity maturation. We propose that the expansion of these rare types of memory B cells may explain why most people did not become severely ill, even in the absence of preexisting protective antibody titers. Recent studies in mice strongly support the idea that consecutive immunizations with antigens from divergent", "Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: After 1 month, we retested this scale with a sample of 92 undergraduates , and the retest coefficients of the three subscales were 0.83 , 0.70 , and 0.64 . The retest coefficient of the total scale was 0.86. According to Hair, Babin, Money, and Samouel , the reliability of the scale is acceptable. Title: Human resource crises in German hospitals\u2014an explorative study", "Passage: The first item had to be answered on a five-point Likert scale . For the second and third item, the participants had to move a slider from 0% to 100%. The last item had to be answered on a seven-point Likert scale from absolutely not dangerous to extremely dangerous . Afterwards, the acquired causes of each crisis were introduced with the following sentence: \"How important do you evaluate this event for the occurrence of the crises?\" Answers were made using a seven-point Likert scale from 1 = absolutely unimportant to 7 = extremely important. Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak", "Passage: All articles were printed, scores were written in the margins for each article and later entered into an Excel spreadsheet . Two individuals scored each article; one author scored all articles while the second reading was divided among research assistants who scored a clean copy of the article to assure they were not influenced by the prior scoring. Inter-reader variation was calculated by taking the total number of topics and subtopics scored for agreement , subtracting the number of discordant topic points , then dividing by the total possible points. Scores were compared across readers and ranged from 95.4-100% inter-reader Title: Trajectories of School Recovery After a Natural Disaster: Risk and Protective Factors", "Passage: Scale Score. The raw scores of the TAKS taken by students were converted to scale scores. The TEA used the following formula to transform the raw score received by a student on a TAKS test to a scaled score: SSj \u00bc \u00fe T2, \"where SSj the scale score for student j, uj the Rasch partial credit model proficiency level estimate for student j, and T1 and T2 scale score transformation constants that establish the scale score system,\" . The T1 and T2 constants varied by subject and grade level for every year the TAKS was administered .", "Title: Key mechanisms governing resolution of lung inflammation\nPassage: t m a n n e r . M. tuberculosis-induced NETs were decorated with key ETotic markers such as histone H2A, H2B and NE and were able to trap but not kill M. tuberculosis . Granulomas are an important and hallmark feature of tuberculosis and are generally caused by mycobacterial or fungal infections. These prominent structures represent a key immune response to foreign material that is too large to be cleared by other immune defence processes. For an in-depth review of the role of ETosis during lung inflammation, refer to Cheng and Palaniyar . Interestingly, there appears to be a Title: Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype", "Passage: The course of M. tuberculosis infection in the standard \"mouse model\" is often contrasted with the diversity of TB-related disease that is apparent in other species. For example, while M. tuberculosis can replicate continually at some sites in the lungs of cynomolgus macaques, M. tuberculosis is efficiently killed in most of the granulomas . These studies are consistent with observations from human autopsies, which similarly suggest that M. tuberculosis is eradicated from many granuloma and only replicates in a minority of sites . In contrast, with the exception of a few susceptible substrains , M. tuberculosis infection of standard laboratory Title: Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics", "Passage: Pulmonary TB is characterised by granuloma formation, caseation and ultimately cavitation, reflecting a complex interplay between distinctive components of the innate and acquired immune response and the pathogen . Traditional serological analysis of single circulating proteins is notoriously unreliable for TB diagnosis . In contrast, patterns of circulating proteins could provide an accessible readout of pathophysiological status. Discovery of such discriminatory biomarkers could open the way for the development of new point-of-care tests based on a lateral flow format such as dipsticks. Title: Altered microRNA expression and pre-mRNA splicing events reveal new mechanisms associated with early stage Mycobacterium avium subspecies paratuberculosis infection", "Passage: by inhibiting SPARC expression. Proliferation of endothelial cells after MAP infection is one of the causes of granuloma formation 6 , which is a significant feature of JD in ruminants 1 . Granulomas mainly consist of MAP-infected macrophages and provide an organized and protected microenvironment within which MAP can establish a persistent infection in the host 41 . Although, no granulomas were histologically visible at one-month post-infection in our study , a previous study reported that granulomas were observed at 3 to 4 weeks after mycobacteria infection 42 . Nevertheless, this study revealed that MAP infection promotes endothelial cell proliferation", "Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic\nPassage: It has become accepted wisdom that serum hemagglutination inhibition titers \u22651:40 or, even better, \u22651:80, are correlates of protection against natural infection. Support for this idea comes from epidemiologic studies and from study of passive immunotherapy with immune serums in humans and experimental animals. Yet it is far from clear that HI antibody alone reliably prevents asymptomatic or symptomatic infection in humans. In experimental human challenge studies, HI antibody is not a reliable determinant of protection , and some persons with significant levels of HI antibody can be repeatedly infected by the same virus to which they have preexisting antibody Title: Virus-Vectored Influenza Virus Vaccines", "Passage: induction of humoral responses to the hemagglutinin protein, the major surface and attachment glycoprotein on influenza. Serum antibody responses to HA are measured by the hemagglutination-inhibition assay, and the strain-specific HI titer is considered the gold-standard correlate of immunity to influenza where a four-fold increase in titer post-vaccination, or a HI titer of \u22651:40 is considered protective . Protection against clinical disease is mainly conferred by serum antibodies; however, mucosal IgA antibodies also may contribute to resistance against infection. Split virus inactivated vaccines can induce neuraminidase -specific antibody responses , and anti-NA antibodies have been associated with protection from infection Title: High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults", "Passage: HI assays were performed in duplicate against the influenza vaccine strains in the 2015-2016 Northern Hemisphere influenza vaccine components according to the standardized protocol by the world health organization. Seroprotection was defined as an HI titer of \u2265 40. Subsequent flu infection was defined as either the detection of influenza RNA in a swab sample by RT-PCR or a 4-fold or greater rise in HI titer, with a second titer of at least 40. Title: Cross-subtype Immunity against Avian Influenza in Persons Recently Vaccinated for Influenza", "Passage: Human sera from the same donors were tested for HI activity against both vaccine and infl uenza preparations and for neutralization activity against infl uenza virus. Individual titers are reported in Figure 3 . A 4-fold rise in HA antibody titer is considered noteworthy, and after vaccination most donors showed a noteworthy rise of HI titers against vaccine preparation, as indicated by an asterisk . HI titers against infl uenza virus remained at undetectable levels after seasonal vaccination , but a rise of neutralization titer >20-fold over baseline was observed in 13 of 38 donors . All but 1 study", "Title: Impact of acyclovir use on survival of patients with ventilator-associated pneumonia and high load herpes simplex virus replication\nPassage: Overall, 66 of 89 patients were tested for CMV replication together with HSV. CMV replication could be detected in 14/66 patients but had no effect on median ICU survival . Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management\nPassage: is 65-fold more potent against AdV than CDV in vitro with a low risk of myeloidor nephrotoxicity, but gastrointestinal side effects are more common. 112 In a retrospective study of 13 immunocompromised patients given BCV for AdV disease after failing or intolerance to i.v. cidofovire nine patients demonstrated a virological response , which was defined as a 99% drop from baseline or undetectable AdV DNA in serum by week 8. Patients with VR had longer survival than those without VR . 113 Title: Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome", "Passage: On day 30 after study inclusion 52 patients had died, 209 The quantitative PCR results were calibrated according to the CMV WHO standard; viral loads greater than or equal to 1000 IU/mL were denoted 'high reactivation'. Viral loads of 100-999 IU/mL were denoted 'low reactivation', and undetectable loads or viral loads below 100 IU/mL were denoted 'no reactivation' were successfully weaned, and 10 remained still on mechanical ventilation . In crude analyses, patients with CMV reactivation had both a longer duration of mechanical ventilation vs. 8 days; p \\ 0.01) and higher mortality vs. 29 of 197 patients; p \\ Title: Cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis", "Passage: to demonstrate that immunocompetent critically patients with CMV infection could benefit from antivirus therapy. And there are a number of side effects of antiviral drugs, such as hematologic complications , renal dysfunction, mental disorders . Therefore, giving antiviral drugs to critically ill patients should be considered cautiously in terms of advantage-disadvantage ratio. To address this issue, there are two ongoing, blinded, randomized placebo-controlled clinical trials of an antiviral drug with activity against CMV in critically ill patients in the ICU .", "Title: Paediatric nurses\u2019 general self-efficacy, perceived organizational support and perceived professional benefits from Class A tertiary hospitals in Jilin province of China: the mediating effect of nursing practice environment\nPassage: The results of the proposed model showed that there was no negative variance and a large standard error in model, so the model did not violate the identification rules. This model' s fitness and the actual data were good from the whole index of the mode. The absolute fitness index, value-added fitness index and simple fitness index all met the adaptation standards . Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: such strong performance were found for the majority of our sendout or in-house tests by either of our two complementary approaches. Thus while the rules we found can inform clinical decision-makers, the information they provide rarely replaces the information obtained from actually performing these tests. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data\nPassage: of standard statistical techniques can turn this relationship into actionable decision-support rules-or whether progress toward better laboratory utilization might instead lie elsewhere. Title: Paediatric nurses\u2019 general self-efficacy, perceived organizational support and perceived professional benefits from Class A tertiary hospitals in Jilin province of China: the mediating effect of nursing practice environment", "Passage: The Perceived Organizational Support Scale was developed by Eisenberger and compiled by Chen ZX . Zuo HM appropriately modified the original scale for nurses. The scale contains 13 items, including 2 dimensions, namely, emotional support and instrumental support . On a 5-point scale, the responses ranged from 1 to 5 , and the total score was between 13 and 65 points. A higher score implies a stronger POS. The Cronbach's alpha coefficient was 0.921.", "Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies\nPassage: Text: Microtubule severing enzymes are a family of AAA-ATPase proteins that participate in fundamental cellular processes such as mitosis, ciliary biogenesis and growth cone motility. In neurons this family is known to control such processes as axonal elongation 1 and synaptic development. 2 In addition, mutations in microtubule severing enzyme genes SPG4, KATNB1 and KATNAL2 are associated with hereditary spastic paraplegia, cerebral malformations and autism, respectively, and mutations in Fign cause a range of phenotypes in mice. 7 Currently the microtubule severing enzyme KATNAL1 is poorly characterised and it is not yet understood how the enzyme functions in the nervous Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: Microtubule severing enzymes are a family of AAA-ATPase proteins that participate in fundamental cellular processes such as mitosis, ciliary biogenesis and growth cone motility. In neurons this family is known to control such processes as axonal elongation 1 and synaptic development. 2 In addition, mutations in microtubule severing enzyme genes SPG4, KATNB1 and KATNAL2 are associated with hereditary spastic paraplegia, cerebral malformations and autism, respectively, and mutations in Fign cause a range of phenotypes in mice. 7 Currently the microtubule severing enzyme KATNAL1 is poorly characterised and it is not yet understood how the enzyme functions in the nervous system. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: Microtubule severing enzymes play diverse roles in the nervous system. 1, 2 However, at present the microtubule severing enzyme Katnal1 is poorly defined in the context of CNS development and function. Here we present a detailed phenotypic analysis of Katnal1 1H and show that the mutation is associated with changes in circadian rhythms, sleep and behaviour. Furthermore we demonstrate that defects in brain histopathology, neuronal migration and neuronal morphology underlie these phenotypes. Finally we also demonstrate that Katnal1 1H causes a range of defects in the motile cilia of ventricular ependymal cells. The data we present here are the first Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: Microtubule severing enzymes play diverse roles in the nervous system. 1, 2 However, at present the microtubule severing enzyme Katnal1 is poorly defined in the context of CNS development and function. Here we present a detailed phenotypic analysis of Katnal1 1H and show that the mutation is associated with changes in circadian rhythms, sleep and behaviour. Furthermore we demonstrate that defects in brain histopathology, neuronal migration and neuronal morphology underlie these phenotypes. Finally we also demonstrate that Katnal1 1H causes a range of defects in the motile cilia of ventricular ependymal cells. The data we present here are the first", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: severe forms of HFRS and HCPS have begun to achieve sufficient mass as to induce, through PAMP-PRR interactions and other means, the expression of proinflammatory cytokines . For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed, and yet it is often not appreciated that the expected preferential tissue tropism of HFRS-associated viruses and their HCPS-associated counterparts for the renal and pulmonary beds, respectively, is not as one would predict through the manifestations of the two diseases. Title: Leave entitlements, time off work and the household financial impacts of quarantine compliance during an H1N1 outbreak", "Passage: This has implications both for power and the risk of Type II errors. Nonetheless, the response rate is comparable to that achieved in other similar school-based studies of pandemic influenza in the US and England and our study had the advantage of covering a larger number of affected schools than most other studies. As we showed in an earlier publication from this study, we received a disproportionately low level of response from less advantaged schools, reducing the generalisability of our findings and potentially biasing our results . It could be expected that non-responding households were less likely to have access Title: Paediatric nurses\u2019 general self-efficacy, perceived organizational support and perceived professional benefits from Class A tertiary hospitals in Jilin province of China: the mediating effect of nursing practice environment", "Passage: The Perceived Organizational Support Scale was developed by Eisenberger and compiled by Chen ZX . Zuo HM appropriately modified the original scale for nurses. The scale contains 13 items, including 2 dimensions, namely, emotional support and instrumental support . On a 5-point scale, the responses ranged from 1 to 5 , and the total score was between 13 and 65 points. A higher score implies a stronger POS. The Cronbach's alpha coefficient was 0.921. Title: Local risk perception enhances epidemic control\nPassage: is underestimated early in the epidemic and overestimated late in the epidemic. An H near one indicates that approximately one infection is averted for every vaccine given. Note that this is an average, and does not necessarily mean that every vaccination prevents infection of the recipient. If each vaccine averts, on average, greater than one infection , then the value of H corresponds to the level of indirect protection achieved by the decision strategy.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: eosinophilic infiltration in the asthmatic airway. The effect is also further compounded by the participation of Th1 and ILC1 cells in the COPD airway; and Th2 and ILC2 cells in the asthmatic airway. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Text: The prevalence of chronic airway inflammatory disease is increasing worldwide especially in developed nations . This disease is characterized by airway inflammation leading to complications such as coughing, wheezing and shortness of breath. The disease can manifest in both the upper airway and lower airway which greatly affect the patients' quality of life . Treatment and management vary greatly in efficacy due to the complexity and heterogeneity of the disease. This is further complicated by the effect of episodic exacerbations of the disease, defined as worsening of disease symptoms including wheeze, cough, breathlessness and chest tightness . Such exacerbations", "Title: Estimating the number of infections and the impact of non-\nPassage: modelled deaths are informed by an infection-to-onset distribution (time from infection to the onset Title: Estimating the number of infections and the impact of non-\nPassage: infection-to-death distribution is therefore given by: Title: Estimating the number of infections and the impact of non-\nPassage: 0.86. The onset-to-death distribution is also Gamma distributed with a mean of 18.8 days and a Title: Estimating the number of infections and the impact of non-\nPassage: to-onset) distribution and the time between onset of symptoms and death . The", "Title: Inference of Transmission Network Structure from HIV Phylogenetic Trees\nPassage: for sexually transmitted diseases very challenging. Title: Computational Approaches and Challenges to Developing Universal Influenza Vaccines", "Passage: The integration of protein functions and structures into evolutionary models has two main challenges: published viral protein structural and functional information may not be available or sufficiently resolved based on current studies; and The assumption of nucleotide site independence in the model cannot capture the biological reality that some sites are linked due to shared function . Some modeling approaches with a protein structure scoring system or partitioning schemes on the protein sequence can potentially overcome these challenges; for example, protein structure has been explored with coarse-grained models for structure prediction, prediction of protein interaction and molecular dynamics simulations of Title: HIV/AIDS prevention in China: A challenge for the new millennium", "Passage: Although positive steps have now been taken by the Chinese government in combating HIV/AIDS, numerous challenges remain. One issue is the structural inadequacy of China's current health care system that was graphically revealed during the SARS outbreak . Tuberculosis offers another pertinent example of how these shortcomings may compound the situation. China now has twice the level of multi-drug resistant tuberculosis of other countries . Providing affordable and accessible health care to the general public has also become increasingly difficult following the introduction of free-market reforms in 1978. In this manner, the rural health cooperatives that once provided health insurance Title: Computational Approaches and Challenges to Developing Universal Influenza Vaccines", "Passage: protein folding . This provides the statistical potential like a scoring system for sequence-structure compatibility, which can be used to evaluate the probability of fixation of a given mutation and improve the precision of ancestral reconstruction . However, few studies have incorporated protein structural information into the evolutionary analyses. Simple representations of protein functional and structural domains have been used so far. Hypothetically, novel models with a more complete representation with a full site mapping of the protein functions and structures would yield a better fit. But in a phylogenetic context, structurally informed models are still outperformed by some site-independent", "Title: Furin\u2010mediated protein processing in infectious diseases and cancer\nPassage: The prototypical and best-characterised member of the PCSK family is furin/PCSK3. Since it cleaves basic amino acid motifs, it has also been termed PACE . Furin is expressed by the FUR gene on chromosome 15. Although furin is ubiquitously expressed, its mRNA and protein levels vary depending on the cell type and tissue. High levels can be found in salivary glands, liver and bone marrow, whereas muscle cells express relatively low amounts of furin. 9 Three promoters , each harbouring an alternative transcription start site, have been described . However, the respective transcripts differ only in the first untranslated exon Title: Furin\u2010mediated protein processing in infectious diseases and cancer", "Passage: Although the therapeutic application of furin inhibitors may be full of pitfalls, it is certainly a promising approach that should be further pursued. Future studies will elucidate the role of individual PCSKs and their substrates in disease progression and a better understanding of cellular pathways regulating furin activity may uncover additional targets for therapeutic intervention. Title: Furin\u2010mediated protein processing in infectious diseases and cancer\nPassage: blood. However, this effect does not involve proteolytic cleavage of a specific substrate, but is mediated by a direct binding of PCSK9 to LDL receptors. 8 With two FDA-approved inhibitors for the treatment of hypercholesterolaemia, PCSK9 is also the prime example of a protease that is successfully targeted for therapy. 6 Title: Furin\u2010mediated protein processing in infectious diseases and cancer", "Passage: Furin is a member of the evolutionarily ancient family of proprotein convertases. Their similarity with bacterial subtilisin and yeast kexin proteases has coined the abbreviation PCSK . Humans encode nine members of this protease family , with PCSK3 representing furin . PCSKs are well known for their ability to activate other cellular proteins. The proteolytic conversion of inactive precursor proteins into bioactive molecules has already been described in the 1960s. 3 However, it took more than 20 years until furin was identified as the first mammalian proprotein convertase. 4, 5 To date, more than 200 cellular substrates of PCSKs have", "Title: Innate Immune Sensing and Response to Influenza\nPassage: NK cells possess unique natural cytotoxicity receptors such as NCR1 in mice, and NKp30, NKp44, and NKp46 in humans, involved in recognition of viral-and tumor-associated molecules and activation of NK cells . Influenza virus productively infects human NK cells in vitro . In mouse models of influenza virus infection, there is a substantial increase in the population of activated NK cells expressing CD107a and IFN-c in the lungs, which can lyse influenza virus-infected cells through granzyme B and perforin, and contribute to the virus control . Accordingly, NK cell-depletion or defects in NK cell activity resulted in delayed virus clearance Title: The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition", "Passage: NK cells are innate immune cells providing rapid responses against IAV infection in mice. Their action during the first days of infection has a major impact on survival of infected animals, since an early NK cell depletion induces an increased mortality . NK cells cytotoxicity and cytokine production are tightly regulated by the interplay between inhibitory and activating receptors. Activating receptors, such as Ncr1, have been demonstrated to be critical in the eradication of IAV in mice . Upon recruitment and activation within the lungs ), NK cells can directly kill IAV-infected cells after direct contact, through secretion of cytolytic Title: Innate Immune Sensing and Response to Influenza", "Passage: Consistent with this, in humans, NKp46 and NKG2D-mediated recognition of HA on influenza virus-infected cells induced NK cell-mediated cytolysis of target cells . However, in contrast to these in vitro findings, virus infection was associated with transient deficiency of circulating NK cells, particularly CD56 +++ NK cells, and downregulation of NK cell activity, especially with pandemic H1N1 2009 influenza patients . It is not clear whether the reduced number of NK cells in peripheral blood is a reflection of augmented recruitment of NK cells to the site of infection, the respiratory tract. However, the fatal cases of influenza virus infections Title: IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection", "Passage: for innate immune effectors including natural killer cells, which provide short-term control of viral replication prior to T cell activation . NK cells become activated following the loss of inhibitory signals coupled with positive activating signals resulting in direct or indirect target cell lysis . NK cells are vital in limiting influenza viral replication as depletion of NK cells dramatically increases morbidity and mortality in hamsters and mice , and in humans severe infections with the 2009 pandemic H1N1 virus positively correlated with reduced numbers of NK cells in the lungs . Studies have indicated that the natural cytotoxicity receptors", "Title: Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis\nPassage: We also observe positive selection for dinX on the branch leading to the pathogenic Mycobacteria in our d N /d S analysis . Most organisms use specialized DNA polymerases that are able to catalyze translesion synthesis across sites of damage, including the dinB group of Y family polymerases. There are two dinB-family polymerases in Mtb . Unlike in other bacteria, dinX and dinP expression are not dependent on recA, the SOS response, or the presence of DNA damage, and could therefore serve a novel yet uncharacterized role in Mtb . Title: Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection", "Passage: ranked much lower among the non-DNA damaging compounds , signifying a high specificity of ProTINA predictions . Equally important, ProTINA was able to accurately identify the direction of the drug-induced alterations caused by the DNA damaging compounds. The signs of protein target scores from ProTINA indicated drug-induced enhancement of CDKN1A, PCNA and GADD45A, and attenuation of CCNB1, AURKA and PLK1 , consistent with the expected response of these proteins to DNA damage in Figure 3 . Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders", "Passage: Retinopathy. In retinopathy, SYVN1, syniviolin 1, is involved in endoplasmic reticulum associated degradation. SYVN1 confers diabetic retinopathy resistance. Yang S et al. described this with expression analysis and found lower expression of SYVN1 in diabetic mice 127 . TXNIP, thioredoxin interacting protein, is a thioloxidoreductase. It protects cells from oxidative stress. TXNIP plays crucial role in the inflammation and retinal injuries in early stages of DR 128 . Title: Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection\nPassage: involved in the overall DNA damage repair and its associated pathways . As depicted in Figure 4B , ProTINA ranked these proteins much higher than De-MAND and DE analysis, with DE performing the poorest among the methods considered.", "Title: The Trojan Chicken Study, Minnesota\nPassage: The mean age of those who completed the enrollment questionnaire was 33 years. Eighteen participants were poultry exhibitors, who showed 1-10 birds each . Fifty-five participants of 82 were residents of farms. Title: A survey of knowledge, attitudes and practices towards avian influenza in an adult population of Italy\nPassage: The sample consisted of 683 individuals for a participation rate, defined as the number of completed questionnaires divided by the number of those randomly selected, of 67%. Socio-demographic characteristics of the respondents are reported in Table 1 . The average age was 40.7 years, two thirds were female, almost all were married, the majority had not reached college level education, more than half is inactive or housewife, and one-third has three or more children. Table 3 ). Title: Public awareness of risk factors for cancer among the Japanese general population: A population-based survey", "Passage: A total of 1,355 subjects responded to the survey, with a higher response rate in women than in men . Response rate was lower in the 20s age strata than in the other age groups, but no trend to an increase in response rate with increasing age was observed. Overall, no significant difference in area and age distribution was seen between the sampled population and survey respondents. Response rate tended to be lower among subjects who reside in the Kanto region and in cities other than the 14 metropolises than among other subjects . Title: Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015", "Passage: that of the adults of aged 25-60, and the influenza pandemic patterns appeared highly heterogeneous at each age scale. This phenomenon only appeared during the pandemic, but not in any other peak of the year, such as those in 2011 and 2013-2015. To compare the timing across various age groups, we calculated their phase angle difference for the annual cycle that was consistently observed throughout the study in Fig 3B. The 25-60 age group was found to follow the 0-5 group, with an average delay of 4.1 weeks, ranging from the delay of 2.0 to 6.4 weeks, and to follow", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences . N is also reported to interact with actin microfilaments, and the SUMO-1 protein . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in Title: Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment", "Passage: Despite living in different houses and neighborhoods, the tracked individuals showed a high degree of connectivity, with the largest network component accounting for 96.2% of all individuals and 97.8% of all edges . N ij was projected into its constituent affiliation networks: N L and N P . The degree distributions of N L and N P were best fitted by a truncated power-law distribution of the Table 1 . Glossary of network topology terms used in the manuscript. Title: A multidimensional classification of public health activity in Australia\nPassage: other investors; the links to employment and education; and public health investment by, and outcomes in, other sectors such as transport and housing. Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: It has also been observed that the N protein of several coronaviruses can localize in the nucleolus where it may perturb cell cycle activities of the host cell for the benefit of viral mRNA synthesis . IBV N, for example, appears to target CDK2, cyclins A and D1 for proteasomemediated degradation and cause the accumulation of hypophosphorylated retinoblastoma , resulting in the downregulation of CDK1, cyclins E and B1 .", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 , and 82% with human SARS-CoV BJ01 2003 and human SARS-CoV Tor2 . The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes were shown ). For all these 5 genes, the 2019-nCoV was clustered with lineage B \u03b2CoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: In summary, 2019-nCoV is a novel lineage B Betacoronavirus closely related to bat SARS-related coronaviruses. It also has unique genomic features which deserves further investigation to ascertain their roles in viral replication cycle and pathogenesis. More animal sampling to determine its natural animal reservoir and intermediate animal host in the market is important. This will shed light on the evolutionary history of this emerging coronavirus which has jumped into human after the other two zoonotic Betacoroanviruses, SARS-CoV and MERS-CoV. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The complete genome sequence of 2019-nCoV HKU-SZ-005b was available at GenBank . The representative complete genomes of other related \u03b2CoVs strains collected from human or mammals were included for comparative analysis. These included strains collected from human, bats, and Himalayan palm civet between 2003 and 2018, with one 229E coronavirus strain as the outgroup.", "Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example\nPassage: Thus \u03c8\u00f0t\u00de \u00bc e \u00c0l r t and \u00f0t\u00de \u00bc l r e \u00c0l r t are probability function that the time for an individual to be removed at time t and its corresponding probability density function respectively. The basic reproduction number can be written as the product of the expected excess degree and the expected transmissibility R 0 \u00f0t\u00de \u00bc z 2 z 1 T\u00f0t\u00de. Title: Estimating the number of infections and the impact of non-\nPassage: Averaged across all countries, we estimate initial reproduction numbers of around 3.87 , Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: totally susceptible population . When R 0 is greater than one, there is a likelihood that the infection will to continue to spread; however if R 0 is less than one, then the infection will eventually die out. For this reason, estimating the basic reproduction number is paramount for assessing the effectiveness of different intervention strategies. Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: are 66 and~2200, respectively, which are about 5 to 10% of the total number of laboratory confirmed cases in the whole epidemic. Using the excess degree of children and adults, the age specific R 0 can be estimated for both children and adults. We showed that R 0 for children is higher than that for adults , which is consistent with other studies ). This implies that school-aged children likely contributed more infections than adults.", "Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research\nPassage: research and requires that researchers reflect upon their own background and position, and how it will affect \"what they choose to investigate, the angle of investigation, the methods judged most adequate for this purpose, the findings considered most appropriate, and the framing and communication of conclusions\" :p483-4. This can entail, for instance, reflecting on how the researcher's status and role may have influenced what the informants disclose and how it is presented to the researcher . We found no explicit discussion of the primary study authors' background or position, including how their studies might have been influenced by these factors, Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust", "Passage: Academic researchers are to a great extent driven by the incentives of their profession, which reward publishing papers in peer-reviewed journals, regardless of whether or not the data are used to improve health outcomes. This necessarily influences the communication of results. High-level, multi-country comparisons have proven attractive to the editors of high-profile journals, The Lancet in particular . Publication in these journals in turn imbues academic estimates with a legitimacy that is not shared by data produced at the country level. Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research", "Passage: We regard this lack of information about and reflection on the context of the studies as a weakness in the studies and connect it to a lack of researcher reflexivity demonstrated by the primary study authors. The authors' contact information indicates that the majority of them held positions at medical faculties and that some of them were Ministry of Health employees. This suggests that they have approached their own study with a public health perspective, focusing on the achievement of herd immunity through patient compliance. The primary study authors' aim of increasing vaccine compliance appears to have influenced their recommendations Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: of homogeneity or assessment of similarity of results across studies was conducted and reported; 9) appropriate weighting of primary studies was conducted; and 10) the author's interpretation of the results were supported by the data . Each criterion is equally weighted and a final methodological score is tallied out of 10. Reviews with an overall rating of eight or more are considered strong, five to seven, moderate, and below four are considered to be weak in methodological quality.", "Title: Haunted with and hunting for viruses\nPassage: Tan and colleagues specifically focused on the newly-emerged MERS-CoV. The virus was identified in 2012 in the Middle East with some exported cases to Europe. In 2013 the virus has been re-emerging and expanding its borders to more European countries. In the initial diagnosis, the pan-coronavirus real-time reverse transcription polymerase chain reaction assay played a very important role for the identification of the causative agents. By using this method, scientists detected an expected-size PCR fragment for the corresponding conserved region of ORF1b of the replicase gene of a coronavirus. This is another example that molecular biology methods played for the Title: Temporal trends in the discovery of human viruses", "Passage: implications. Current trends are consistent with a pool of at least 38 undiscovered species that will be reported at an average rate of at least approximately one per year to 2020. In this context, it is worth noting that three new species were reported in 2007: two polyoma viruses, Ki and Wu, and a reovirus, Melaka . Other viruses may have been reported but not yet classified. In practice, future rates of discovery will, of course, be affected by any major advances in virus detection technology or by any major shifts in the effort expended on virus discovery programmes. Tissue Title: Viral infection detection using metagenomics technology in six poultry farms of eastern China", "Passage: The NGS sequencing data were compared with the GenBank non-redundant protein databases, and the results showed that one to four species of viruses excluding phage were detected in each pool of samples . AIV was detected in all the farms, and the results of the AIV subtype analysis using Rapid Typing and Analysis Software of Influenza A Virus are shown in Table 3 . Five H9N2 and one H3N8 AIVs were detected in the farms. IBV was detected in three farms . The chicken farm in Jiangsu province had the most kinds of viruses , and a BLASTx analysis of Title: DisCVR: Rapid viral diagnosis from high-throughput sequencing data", "Passage: A total of 48/89 of the samples had been shown to contain viruses by RT-PCR, and the remaining 41/89 lacked all viruses tested. Considering only the samples in the set of eightynine for which DisCVR identified 850 k-mers for the top hit, the following findings were made. DisCVR identified the viruses that were detected by RT-PCR in 32/48 of samples . It did not detect viruses in samples in which no viruses had been found by RT-PCR in 22/41 of samples . It detected viruses in samples in which no viruses had been detected by RT-PCR in 19/41 of samples", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: When biomedical innovations fall into the 'Valley of Death', patients who are therefore not reached all too often fall with them. Being entrusted with the resources and expectation to conceive, deliver and communicate dividends to society is both cherished and eagerly pursued at every stage of our careers. Nevertheless, the road to research translation is winding and is built on a foundation of basic research. Supporting industry-academia collaboration and nurturing talent and skills in the Indo-Pacific region are two of the four pillars of the National Innovation and Science Agenda. 2 These frame Australia's Medical Research and Innovation Priorities, which Title: Frontiers in antiviral therapy and immunotherapy", "Passage: include antimicrobial resistance, global health and health security, drug repurposing and translational research infrastructure, 15 capturing many of the key elements of this CTI Special Feature. Establishing durable international relationships that integrate diverse expertise is essential to delivering these outcomes. To this end, NHMRC has recently taken steps under the International Engagement Strategy 16 to increase cooperation with its counterparts overseas. These include the Japan Agency for Medical Research and Development , tasked with translating the biomedical research output of that country. Given the reciprocal efforts at accelerating bilateral engagement currently underway, 17 the prospects for new areas of international Title: Australian public health policy in 2003 \u2013 2004", "Passage: Amongst health conditions affecting Australians, breast cancer received the most attention, with the National Breast Cancer Centre being funded to develop a partnership approach to the review and dissemination of new information, along with information, support and management initiatives for rural women diagnosed with breast cancer. Hepatitis C also received some attention, with funding for national education and prevention projects. Financial support was offered for the SARS efforts that had been undertaken by states and territories, in particular for providing medical personnel at international airports. A clear process for assessing priorities under the broad banded National Public Health Program was Title: Australian public health policy in 2003 \u2013 2004", "Passage: During the course of the Howard Government, there has been a gradual process of re-casting the \"landscape\" of interest groups and policy constituencies. Strong support for breast cancer and zero-tolerance on illicit drugs contrasts sharply with the delays experienced in renewal of the National HIV/Hepatitis C Strategy. The new prominence given to meningococcal vaccine, child health and obesity creates space for other interest groups: even if the re-framing was shaped by nutrition and physical activity lobbies, other clinical interests have been brought into the picture. These developments illustrate how 'political' considerations are important in determining 'public health policy'.", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: access areas for medical personnel and a dressing area for technologists. The clean area Title: Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center\nPassage: in the ICUs group. The overall daily hospital bed occupancy rate was approximately 92% during the study period. In the busy surgical wards, if the surface is not visibly dirty, it may not receive attention or wiping. It is important to simplify the cleaning workflow and strengthen wiping of the hightouch surfaces in a timely manner. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: symptoms of COVID-19. Pregnant staff must be assigned to the clean area. Title: Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center", "Passage: Phase 1 served as a baseline phase, during which there were no additional interventions. At this medical center, routine disinfection of the surfaces in specific areas close to patients, such as bed rails and overbed tables, are disinfected daily in the ICUs and weekly in the general wards. Areas distant from patients, only light switches, door knobs and bathrooms are disinfected daily in all types of wards. The disinfectant is 600 ppm sodium hypochlorite that diluted by the ESWs according to the manufacturer's instructions for routine disinfection and terminal cleaning/ disinfection.", "Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires\nPassage: Plasmodium falciparum is the mosquito-borne parasite that causes malaria. According to the CDC, malaria caused an estimated 216 million cases of malaria and 445,000 deaths worldwide in 2016. With repeated exposure, older children and adults slowly develop resistance to severe illness and death but never achieve complete resistance to infection . In humans, P. falciparum infection generates a long-lived atypical Bmem response which develops slowly, after many years of malaria exposure, and is limited in magnitude . The neutralizing IgG + Abs produced by atypical Bmem seen during malaria infection in adults differ in their V region repertoire from Abs Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: A new paradigm in malaria vaccine development is also emerging with the discovery of IgM+ and IgD+ memory B cells targeting the Merozoite Surface Protein 1, that rapidly respond to malaria re-infection . Further, highly potent neutralizing antibodies targeting a novel and conserved site on the Circumsporozoite Protein have been isolated from B cells . Together, these examples demonstrate the importance of studying antigen-specific humoral responses to infectious diseases. The solutions to the crystal structures of surface proteins for a variety of pathogens, the conformational stabilization of these antigens, and the application of the methods summarized in this review, to Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: A new paradigm in malaria vaccine development is also emerging with the discovery of IgM+ and IgD+ memory B cells targeting the Merozoite Surface Protein 1, that rapidly respond to malaria re-infection . Further, highly potent neutralizing antibodies targeting a novel and conserved site on the Circumsporozoite Protein have been isolated from B cells . Together, these examples demonstrate the importance of studying antigen-specific humoral responses to infectious diseases. The solutions to the crystal structures of surface proteins for a variety of pathogens, the conformational stabilization of these antigens, and the application of the methods summarized in this review, to Title: Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein", "Passage: to inhibit the entry of malaria parasite within the human host body 23,24 . B-cell epitope mapping. B-cells are a key player of humoral immunity. An epitope corresponding to the B-cell receptor plays an important role in vaccine design following antibody production 33 . Therefore, BCPREDS server was used to reliably predict the linear B-cell epitopes where BCPRED was the selected prediction method 23 . Total 14 B-cell epitopes of 20mer length were predicted among the primary input sequence of final vaccine construct. Among them, only 11 epitopes were selected and finalized because of their high score of 1.0 .", "Title: Viral factors in influenza pandemic risk assessment\nPassage: adaptation, but \"human-adapting\" mutations at these residues do not always change receptor-binding specificity; it depends on the genetic background. Similarly, amino acid residues 627 and 701 of the PB2 protein are often involved in human adaptation, but both carried the \"avian-adapted\" residue in the 2009 H1N1 pandemic strain. When these changes were introduced individually or together in the laboratory, the resulting polymerase showed greater activity in a minigenome assay, but replication was unchanged or attenuated in vitro, in mice, and in ferrets . After the pandemic strain was identified and its anomalous residues at these sites noted, other sites within Title: Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures", "Passage: induction. Our experimental findings explain why many H7N9 virus isolates from humans have one or other of these mammalian adaptation mutations in PB2. Title: Viral factors in influenza pandemic risk assessment\nPassage: be observed in other strains that are not used in the experiment. A recent report shows a related way forward: the recreation of the steps of mammalian adaptation using viruses whose HA and NA are already circulating in humans . Such loss+gain-of-transmissibility experiments reconstruct the properties of naturally occurring seasonal human strains, from laboratory-generated, avian-adapted precursors. Reconstructing such seasonal strains should pose a risk similar to that of working with the seasonal strains themselves, less than that of a novel subtype. A 2011 report employed a similar strategy, demonstrating the importance of HA activation pH in mouse adaptation by selection Title: Viral factors in influenza pandemic risk assessment", "Passage: single mutation for risk prediction ; viruses with the avian-like residue have also been isolated from zoonotic human cases of H5N1, H7N9, and H9N2 infections . On the other hand, the concept that adaptation of the polymerase is necessary for sustained human transmission is validated by findings that the 2009 pandemic strain had adapted to replication in human cells by changes other than E627K within the polymerase . Identification of biophysical mechanisms common to mammalian-adaptive mutations may in the future provide the basis for new biological or biophysical assays of polymerase function to inform risk predictions.", "Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus\nPassage: In this study we examined small mammal populations in 5 forested sites over a 3-year period, October 2002 through September 2005. We monitored mammal species diversity, deer mouse densities, and SNV infection prevalence in the mammals to test the hypotheses that 1) areas of higher mammal species diversity would exhibit lower prevalence of SNV infection in host populations, 2) areas of higher host density would contain higher infection prevalence of SNV in the host populations, and 3) vegetative factors could be related to prevalence of SNV infection among deer mice. Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus", "Passage: Population densities fluctuated synchronously at all sites, yet infection prevalence increased significantly at only 1 site, which suggests that factors other than density alone are involved in disease transmission. If, as hypothesized, transmission were through aggressive encounters , SNV would spread most efficiently in an ecosystem composed solely of deer mice, where every encounter would be a potential disease-transmitting encounter. As more spe-cies, and more individuals within those species, are added to the community, the number of potential disease-transmitting encounters decreases because species other than deer mice are nonhost species. This type of decreased intraspecies interaction has been termed \"encounter Title: Predicting wildlife reservoirs and global vulnerability to zoonotic Flaviviruses", "Passage: in the top 5% of predicted species even though Macaca sylvanus is a known host for WNV 14, 15 and Ateles paniscus, and Sapajus apella have been detected positive for SLEV 15, 16 . Overall, two regions, North America and central Europe, showed high species richness of predicted hosts of Group 2 viruses compared to other regions . When the model for WNV, SLEV, and USUV was run by relabeling species as positive only when they were found positive by PCR or virus isolation, the model predicted higher mean probabilities for species from the orders Accipitriformes, Anseriformes, Carnivora, Charadriiformes, Galliformes, Title: Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants", "Passage: SINV strains , indicated that the regions of interest exhibited few SNPs. Numerous residues within the C:R interaction sites were absolutely conserved; furthermore, the overall incidence of SNPs was on average comparable to or below neighboring sequences that were not identified as C:R interaction sites.", "Title: Making sense of perceptions of risk of diseases and vaccinations: a qualitative study combining models of health beliefs, decision-making and risk perception\nPassage: ten percent. Others gave figures of more than fifty percent of those who got the disease would have to die for them to be concerned. Title: Mortality, morbidity and health in developed societies: a review of data sources\nPassage: Cyprus at 78% in 1997 and at 86% in 2011, while it was 100% at both dates in Sweden . And one should also point out the difficulty, as with all classifications, in reaching univocal solutions in the ICD. Title: CDC Summary 21 MAR 2020,\nPassage: cases in the United States by age group found that 80% of deaths were among adults 65 years and older with the highest percentage of severe outcomes occurring in people 85 years and older. Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: % if they were to have a chronic illness that affected them daily. Public figures were 62 % and 48.8 % respectively. People of African origin were less likely to want CPR if they had a chronic illness, compared to Caucasians. Those who went to university were more likely to want to discuss CPR with a doctor. Less than 3 % surveyed had a do not attempt resuscitation in place.", "Title: Bone Regeneration Based on Tissue Engineering Conceptions \u2014 A 21st Century Perspective\nPassage: the use of large animal models has disadvantages as well, including the high cost and maintenance expenses, extensive housing and space requirements, relatively long life spans and lower bone turnover rates , difficulties in standardisation to generate large, homogenous samples for statistical testing as well as various ethical concerns depending on the species used . But despite several disadvantages, it is inevitable to perform the final pre-clinical in large animals, as realistically as possible, with relevant loading conditions and with similar surgical techniques as used in the final procedure in humans . Large animal models provide mass and volume challenges Title: Animal models to improve our understanding and treatment of suicidal behavior", "Passage: aspect of developing an animal model approach to the study of suicidal behavior is to be realistic regarding what a particular model is measuring. The credibility of specific animal models as they pertain to human mental conditions are commonly evaluated as to whether they demonstrate face, construct, and predictive validity. 24, 25 Face validity refers to phenotypes that contain similarities to humans who have the condition. Construct validity refers to processes that result in human pathology and are recapitulated with the model. Predictive validity relates to the capacity of a model to make predictions about the human condition. A model Title: Animal models to improve our understanding and treatment of suicidal behavior", "Passage: Animal models for studying complex behaviors have been very successful in guiding research in humans, which has led to important discoveries of clinical relevance. In addition, animal studies have been crucial in validating observations from human samples, where studies are limited by ethical considerations and where access to brain tissue is restricted to rare postmortem samples. Furthermore, confounding factors, such as comorbidities, different ages, and different life experiences, are unavoidable in human samples. Although informative of changes associated with patient histories, psychiatric illnesses and suicidal behavior, the use of postmortem brain samples precludes the study of molecular changes occurring at Title: Animal models to improve our understanding and treatment of suicidal behavior", "Passage: disorder itself. This approach limits 'anthropomorphizing' by keeping the focus on neurobiological and pharmacological quantitative aspects that can be translated from humans to animal studies, which commonly use rodents. For example, in animal models of other uniquely human psychiatric conditions such as schizophrenia or depression, experimental animals cannot be labeled as psychotic or depressed. However, approaches that involve the use of model systems are still invaluable in understanding distinct component processes relevant to the disorder, are extensively used in the development of treatment approaches, and are applied toward identifying genetic and environmental influences for such conditions. 23 A critically important", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases.", "Title: Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013)\nPassage: While NMR spectroscopy and X-ray crystallography are the most informative and heavily used methods for understanding protein structure, each has inherent flaws. This is especially evident regarding disordered protein structures, where crystallization requires mostly static structures for diffraction, and NMR is unable to distinguish between different conformational states in an ensemble. Mass spectrometry represents a complementary technique that can be used to generate useful information when examining disordered proteins. Title: The interactome: Predicting the protein-protein interactions in cells", "Passage: dependent on structural changes during complex formation. Therefore, the accuracy of the method is not worse when single protein crystals are used instead of three-dimensional complex structures. A similar approach was proposed by Fariselli et al. , who focused on the selection of important structural features from known protein complexes. Their neural network is able to predict 73% of the interaction residues on the independent benchmark of 226 structures. This work confirms that the use of physico-chemical features of interaction patches and sequence profiles allows for the proper selection of residues important for interactions. Title: A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs)", "Passage: In many cases, it is advisable to use all available crystal structures or multiple NMR models to retrieve promising results. Although the accuracy of NMR structures is poorly validated , they seem to be an acceptable choice for different structural biology and computational modeling challenges . The G-factors calculated with PROCHECK-NMR indicate a lower quality as compared to the X-ray data sets. Nevertheless, the average of -0.28 point toward usual dihedral angles and main-chain covalent forces. Several tools were developed to facilitate the selection of a diverse set of representative protein structures . In the absence of experimental structural ensembles, Title: The interactome: Predicting the protein-protein interactions in cells", "Passage: protein structure prediction allow the introduction of a complementary approach that will use predicted 3D models together with sequence features in order to correctly pair potentially interacting proteins. For instance, the MetaBASIC algorithm developed by Ginalski et al. compares the sequence profiles of two proteins enriched by their predicted secondary structures. Such alignments of query sequences with proteins of known structure allow for quick mean resolution 3D model creation and optimization. The prediction of protein-protein interactions is a difficult problem when an analysis of both the protein sequences and known three-dimensional structures is needed. There are at least two reasons", "Title: Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy\nPassage: The cell cycle represents an integrated series of events that regulates complex processes including cell proliferation, cell division and DNA replication, regulated by a complex hierarchy of genetic and metabolic networks which involves several transition states of varied lengths and checkpoints . The stages of the cell cycle are as follows: synthesis phase , a period where DNA replication occurs; gap phase 2 , during which proteins required for mitosis are produced; mitosis phase , a period where chromatin condensation, nuclear envelope breakdown , chromatid separation, and cytokinesis happens; gap phase 1 , in which genes necessary for DNA replication Title: Marine Organism Cell Biology and Regulatory Sequence Discoveryin Comparative Functional Genomics", "Passage: well understood . Furthermore, individual genes often are part of a broader, coordinately regulated network of genes that function to elicit a set of cellular responses . Through such mechanisms, ligands may, for instance, induce their own metabolism or export, a process that further complicates understanding of gene regulation and that also has critical implications for models of pharmacokinetics and drug efficacy. Title: Marine Organism Cell Biology and Regulatory Sequence Discoveryin Comparative Functional Genomics", "Passage: Transcriptional regulation involves complex interactions of diverse proteins, or transcription factors, with specific DNA sequences in the noncoding regions of target genes. Furthermore, cells respond to environmental stimuli and to developmental signals by altering expression of gene networks. The limited number of transcription factors suggests that few, if any of these proteins exert their activity exclusively on a single gene; rather, they bind to conserved sites in several genes to coordinate their expression . In situations in which there are no clinically acceptable inhibitors or other modulators of clinically relevant proteins, elucidating mechanisms by which these genes are regulated and Title: Marine Organism Cell Biology and Regulatory Sequence Discoveryin Comparative Functional Genomics", "Passage: Mechanisms by which expression of a single gene is regulated can be extremely complicated. Multiple phosphorylation-or ligand-dependent nuclear receptors that homo-or heterodimerize may be required to achieve activity. Each of these receptors may have different activation specificity or duration, even when acting via the same regulatory DNA sequence such as classical proximal promoter elements. These receptors may also work in combination with other transcription factors that function at sites more distal from the proximal promoter or in introns. Alternatively spliced transcripts represent another complex aspect of gene expression regulation that is influenced by extracellular and intracellular signaling but is not", "Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.\nPassage: Text: Anticoccidial resistance , which develops mainly as a result of intensive long-term use of anticoccidial drugs, occurs widely in poultry production and has also been identified in Cystoisospora suis in piglets . In addition, a field method for the evaluation of reduced anticoccidial efficacy in ovine Eimeria spp., the faecal oocyst count reduction test , has recently been developed and indicated that the efficacy of toltrazuril is reduced in some Norwegian sheep flocks . Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.", "Passage: The World Association for the Advancement of Veterinary Parasitology guidelines for evaluation of ACE in mammals , states that there is a need for verified methods for evaluation of ACE. Field methods for assessment of drug efficacy, such as the FOCRT and the faecal egg count reduction test used to evaluate anthelmintic efficacy , give only an indication of reduced efficacy, and need verification through controlled efficacy trials . In addition, due to the variation in pathogenicity between ovine Eimeria spp., the differentiation of species should be considered separately . Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.", "Passage: Future studies are necessary in order to develop a commercial vaccine against ovine Eimeria spp. Therefore, current efforts should focus on identifying ACE, and maintaining the efficacy of toltrazuril in susceptible flocks. Management strategies that decrease the need for anticoccidials by reducing the infection pressure, possibly achieved by applying strict hygienic measures, and improved flock and pasture management should be actively encouraged by veterinarians and agricultural policy incentives . Additionally, farmers should be informed about the importance of correct drenching techniques, including dosage estimation and drench gun calibration, as these have been shown to be inadequate in several farms . Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.", "Passage: Confirmation of the spectre of resistance in ovine Eimeria species increases the urgency of identifying alternative treatments and optimising other control strategies. The anticoccidial effects of different plants and natural extracts, such as sainfoin , carob pods , pomegranate peel extract, grape seed proanthocyanidin extracts, and different natural antioxidants, have been investigated in vivo and in vitro in different hosts . However, none of these bioactive substances have, as yet, been brought to the market for the prevention of clinical coccidiosis. In addition, there are vaccines available for avian Eimeria spp. , and successful immunisation of goat kids with attenuated", "Title: A potent human neutralizing antibody Fc-dependently reduces established HBV infections\nPassage: Antibody concentrations. The antibody concentrations in serum samples were measured by ELISA using antibody standards with known concentrations. Note, for dpi 40 and dpi 54, the blood samples were collected at three days after Ab administration; for dpi 60, the blood samples were collected 1 hr after Ab administration. The horizontal dotted lines indicate the lowest detection limits; the vertical dotted lines and the grey-shaded areas indicate the treatment window . IHC staining of human cytokeratin-18 and HBsAg in serial sections of liver tissues from sacrificed hFRG mice at the end of the experiment . Intrahepatic HBsAg was detected by Title: A potent human neutralizing antibody Fc-dependently reduces established HBV infections", "Passage: at the starting point of treatment. Note that both 2H5-A14 and 2H5-A14-DANA treated mice had comparable serum antibody concentrations at all time points tested and had comparable human albumin levels both before viral challenge and at 80 dpi . Liver tissues collected at the end of the experiment were used for IHC staining of HBsAg and Southern blotting of viral DNA and cccDNA. Consistent with our sera-based measurements, liver tissues from 2H5-A14-treated but not 2H5-A14-DANA-treated mice had greatly reduced levels of HBsAg comparing to the control mice . No significant histopathological changes related to the treatment were observed. Southern blotting Title: A potent human neutralizing antibody Fc-dependently reduces established HBV infections", "Passage: 5 -figure supplement 1, intrahepatic HBsAg were detected using a mouse mAb against Hepatitis B Virus Surface Antigen , followed by HRP conjugated anti-mouse IgG1 . DAB substrate kit was used for developing the HBsAg staining signals, nuclei were stained by Hematoxylin. Consecutive tissue sections were immunostained using a human-specific cytokeratin-18 mouse monoclonal antibody, clone DC10 to visualize human hepatocytes. DAB substrate kit was used for developing the hCK18 staining signals, nuclei were stained using Nuclear Fast Red . Title: A potent human neutralizing antibody Fc-dependently reduces established HBV infections", "Passage: DNA and RNA levels relative to the two control groups . In addition, human albumin levels and alanine aminotransferase activities in mouse serum samples were monitored throughout the study period. There were no significant differences between 2H5-A14 treated group and other groups including vehicle control, 2H5-A14 prophylaxis and HBIG control groups . Liver tissues collected at the end of the experiment were used for immunohistochemical staining of HBsAg and HBcAg, Southern blotting of viral DNA and cccDNA, and Northern blotting of viral RNA. Consistent with our sera-based measurements, liver tissues from 2H5-A14 prophylaxis group animals had no detectable HBsAg and", "Title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans\nPassage: Bats, members of the mammalian order Chiroptera, have evolved a range of characteristics that allow them to adapt to changing environmental conditions. They are the only mammals capable of powered flight, most bat species undergo torpor to conserve energy and species that inhabit high northern latitudes hibernate for up to eight months with body temperatures below 10uC . Bats are extremely diverse, making up a fifth of all known mammalian species. They occupy a variety of niches across most of the world where they contribute in many ways to ecological balance . Title: A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses", "Passage: Bats belong to the order Chiroptera, one of the most abundant, diverse and widely geographically dispersed groups of mammals. This order includes about 1,200 species, accounting for almost 25% of class Mammalia. Interest in these animals is increasing, as they are thought to play an essential role in ecosystem ecology, a domain that has only recently begun to be studied. Bats are highly diverse in terms of their anatomy and lifestyles. Most feed on insects and other arthropods, but some species feed on vertebrates, fish, blood, fruit, nectar or pollen. The order Chiroptera is divided into two suborders: Yinpterochiroptera and Title: Bat Flies and Their Microparasites: Current Knowledge and Distribution", "Passage: Bats are the second most diverse mammalian group after rodents, with \u223c1,390 recognized species across 227 genera . Many bat species play keystone roles in ecosystems, where they are essential to pollination, seed dispersal, and pest control . Several studies have also highlighted their prominent role as pathogen-reservoirs ; viruses being the best studied due to their potential as human pathogens . Bats host more viruses per species than rodents, making them an interesting system for both disease ecology and public health research . Title: Bat Flies and Their Microparasites: Current Knowledge and Distribution\nPassage: There are great ecological differences between bat families. Bat host ecology and physiology, such as roosting habits, body size, and sex can affect bat fly burden and species richness . More studies are again needed to clarify how host traits affect the distribution of microparasite communities of bat flies.", "Title: It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919\nPassage: America, the influenza classed mortality rate declined from 10.2/100,000 in the 1940s to 0.56/100,000 in the 1990s; and the classed mortality rates of 1957-1958 and 1968-1969 influenza pandemics were not remarkably different from the non-pandemic seasons . Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season", "Passage: that observed in our study is also described for the post-pandemic seasons following the three pandemics in the 20 th century. During each of these earlier pandemics, persons younger then 65 years of age initially accounted for a high proportion of influenza-related deaths, followed by a declining proportion of deaths in the postpandemic seasons . Simonsen et al. hypothesised that younger persons may retain long-lasting immunity better than older persons after exposure to a new influenza virus subtype. Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: This makes it necessary to deepen our knowledge of the effect of aging and its interaction with the most prevalent chronic diseases in the elderly and the immune response in order to implement preventive measures to provide better protection of this population group . Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season\nPassage: The peak in mortality rates in persons aged between 55 and 64 years observed during the 2009-2010 pandemic, shifted to older age groups in the 2010-2011 influenza season. Furthermore, the peak in mortality rates in children younger than 15 years of age decreased considerably.", "Title: Can \"presumed consent\" justify the duty to treat infectious diseases? An analysis\nPassage: education and training. In other words, one fifth of the participants either lacked adequate knowledge about the occupational risks when they chose their profession or were not sufficiently informed of these risks during their faculty education and training. This means that the assumption stated in Premise 3 may be wrong for an important proportion of health care workers. It seems reasonable to suggest that the words \"there is a general understanding\" would be misleading if used to characterize a social concept of which the applicability and, indeed, the very existence, are yet to be established by sociological studies. Title: Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features", "Passage: isolated with ancient native populations <200,000. A minimum size or pooled study would be required for substantial incidence counts of late-life NDDs. Study populations of this nature are to be found in Iceland, New Caledonia, San Miguel in the Azores , and a few other islands. \u2022 In order to reveal the causal nature of specific associations, it might be advantageous to study the synergistic effects observed between environmental exposures and selected recognized genetic risk factors for different entities. Title: Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features", "Passage: Accordingly, the purpose of this work was: to complement and anchor the interpretation of each driver with selected results of clinical or animal-model research; to propose etiologic theory pointing to basic mechanisms and specific causal hypotheses testable by study designs, for epidemiologic or experimental research; and in line with recent initiatives, to propose public health developments. Title: Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features", "Passage: proof-of-principle studies would correspond to investigations aimed at confirming that NDDs which are clinically and epidemiologically close by median age at onset, disease duration, age-specific normalized incidence profile and genetic type of change, share environmental risk factors. The study of exposures in the first two decades of life would require approaches separated from that of the same exposures at later ages, with latency analyses being needed in both instances. Simultaneous approaches including two or more NDDs may be advantageous. Identification of selected populations by criteria targeted at optimizing ascertainment of both exposure and outcome, plus identification of randomly selected population", "Title: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan\nPassage: Pulmonary infiltrates were seen on chest X-ray in 127 patients. Thoracic CT-scan excluded a CAP diagnosis in 16.5 % of these 127 patients; on the contrary, thoracic CT-scan revealed a parenchymal infiltrate in 27 % of the 73 patients without infiltrate on chest X-ray. Title: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan", "Passage: identification using naso-pharyngeal PCR that revealed viral respiratory infection in approximately one-third of cases was concordant with values reported in the literature . Therefore, we believe that our results can be extrapolated to most emergency patients suffering from CAP. Title: Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy", "Passage: Pneumonia is seldom a definitive diagnosis, even when histological information is available . Absent a standard, we sought clinically acceptable case definitions that could be reliably abstracted from clinical records. As is both customary and recommended by treatment guidelines , our case definitions required supportive chest imaging. To this common imaging requirement, the Possible-Pneumonia definition added clinical symptoms whereas Pneumonia-in-Plan relied solely on the provider's final diagnostic assessment. Despite these differences, more than 95% of patients with Pneumonia-in-Plan also satisfied the more permissive Possible Pneumonia definition in both our development and validation reference populations, indicating that the two definitions addressed Title: Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan", "Passage: X-ray to explore the chest, only invasive local microbiological samples would have provided a diagnosis with certainty.", "Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections\nPassage: The SARS epidemic began quietly at the turn of the 21st century. In November 2002, a cook in Guangdong Province, China, died from an unidentified illness. He had worked at a restaurant in which meat from wild animals was served. On 27 November 2002 Chinese-language media and internet reports were picked up by Canada's Global Public Health Intelligence Network that indicated a flu-like illness was occurring in China . Unfortunately, the reports were not translated, and China failed to report the occurrence of this illness to the World Health Organization until February 2003. The disease spread to other countries where Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: SARS-CoV and MERS-CoV cause severe disease, but despite the initial R0 estimations of greater than 2.0 for SARS-CoV , and some large outbreaks, neither were as transmissible as initial concerns suggested. SARS-CoV caused 8098 reported cases and 774 deaths in 37 countries before the epidemic was controlled. Control was thought to have been possible because a high proportion of cases were severe, making it easier to rapidly identify and isolate infected individuals. In addition, the virus was present at lower levels in upper airway secretions. There was no secondary transmission in the United States from the 8 imported cases, although Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November. Title: Lessons from the History of Quarantine, from Plague to Influenza A", "Passage: by the emergence of SARS, an especially challenging threat to public health worldwide. SARS, which originated in Guangdong Province, China, in 2003, spread along air-travel routes and quickly became a global threat because of its rapid transmission and high mortality rate and because protective immunity in the general population, effective antiviral drugs, and vaccines were lacking. However, compared with influenza, SARS had lower infectivity and a longer incubation period, providing time for instituting a series of containment measures that worked well . The strategies varied among the countries hardest hit by SARS . In Canada, public health authorities asked persons", "Title: Asthma in the elderly: what we know and what we have yet to know\nPassage: Whereas younger patients with asthma often suffer from allergic rhinitis complaints, elderly patients with asthma often suffer from sinus symptoms, including nasal obstruction, loss of smell and facial pain/headache. A recent Europe-wide epidemiologic study on the prevalence of chronic rhinosinusitis did confirm the well-known association between allergic rhinitis and early-onset asthma, but also demonstrated a clear increased risk to suffer from late-onset asthma in CRS patients . CRS may be phenotyped as CRS without and with nasal polyps , based on symptoms , nasal endoscopy and CT scanning. From those phenotypes, CRSwNP has a clearly increased risk of asthma comorbidity Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Additionally, in patients with asthma and patients with CRS with nasal polyp , viral infections such as RV and RSV promote a Type 2-biased immune response . This amplifies the basal type 2 inflammation resulting in a greater release of IL-4, IL-5, IL-13, RANTES and eotaxin and a further increase in eosinophilia, a key pathological driver of asthma and CRSwNP . Increased eosinophilia, in turn, worsens the classical symptoms of disease and may further lead to life-threatening conditions due to breathing difficulties. On the other hand, patients with COPD and patients with CRS without nasal polyp are more neutrophilic in Title: Asthma in the elderly: what we know and what we have yet to know\nPassage: in Caucasian populations , whereas CRSsNP does not significantly impact on asthma, but may be associated with other lower airway disease . Title: Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review", "Passage: Otolaryngologists should also monitor for chronic rhinosinusitis in PCD patients. CRS is estimated to affect over 50% of patients with PCD 31 and nasal endoscopy can be used to identify polyps which may be exacerbating already poor mucociliary clearance. Nasal polyposis has been observed in up to 15% of PCD patients. 29, 113 Although CRS is not generally life threatening, it substantially affects quality of life. 114 Daily saline irrigation has been demonstrated as safe and beneficial in patients with CRS. 115 Anecdotally, in PCD patients, saline nasal irrigations are beneficial, but studies demonstrating their efficacy are lacking. Given the", "Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies\nPassage: intrapulmonary . We observed that systemic boosting was not as effective as mucosal boosting for induction of mucosal SIgA. Systemic boosting enhanced systemic IgG titers to higher levels than mucosal boosting in IN-primed, but not in IPL-primed mice. Yet, systemic boosting generally stimulated stronger Th1 cellular immunity than mucosal boosting. All the immunization strategies we tested in the current study provided complete protection against influenza virus infection. Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies", "Passage: A potential way to combine the advantages of mucosal and systemic immunization involves prime-boost strategies with mucosal priming and systemic boosting or vice-versa. Several studies have investigated such strategies, but the majority of these make use of DNA vaccines and/or recombinant virus vaccines during priming, boosting or both . So far, little is known about prime-boost strategies for optimization of mucosal and systemic immune responses to protein-based influenza vaccines. A study in horses using an ISCOMadjuvanted influenza vaccine showed that intranasal boosting after intramuscular priming does not have much effect on serum IgG levels, but results in low and transient Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies", "Passage: Despite the advantage of mucosal immunization for the induction of SIgA responses, the mucosal route is suboptimal for the induction of systemic antibody responses . In case of influenza, systemic antibodies are important since they contribute to protection against virus replication in the lungs and are the only correlate of protection so far recognized by regulatory authorities . Furthermore, due to the default Th2oriented nature of mucosal immunity, mucosal immunization shows limited induction of Th1-related antibody subtypes , which are preferable for viral clearance . Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies", "Passage: titers . Meanwhile, pulmonary immunization probably also raises local memory B cell and T cell responses in the respiratory tract, a phenomenon observed upon influenza infection but not upon intramuscular immunization . Thus, mucosal priming is essential for the localization of memory immunocytes to the respiratory tract, which would allow them to respond rapidly to an influenza virus challenge . Moreover, memory B cells primed by the mucosal, but not the systemic, route preferentially express SIgA, which is the major antibody subtype which mediates early immune exclusion and also exhibits cross-protective capacity. Hence, IN/IM, IPL/IM or IPL/IPL immunization regimens should", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies", "Passage: MERS was first noted in Saudi Arabia in 2012, and countries around the Arabian Peninsula are now endemic for MERS-CoV. Patients usually present with fever, cough, chills, sore throat, myalgia, and arthralgia rapidly progressing to pneumonia with over 50% of patients requiring intensive care. About one-third of patients present with diarrhea and vomiting, and acute renal impairment is a striking feature of MERS. Risk factors for poor outcome include diabetes, hypertension, and renal and lung disease. Cases have been exported to at least 26 countries with travel occasionally causing cluster of secondary outbreaks. One such example is the MERS-CoV outbreak Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: recognition of suspect cases. However, during a hospital outbreak in Jeddah, Saudi Arabia, among hospitalized patients only 5 of 53 health care\u2013associated cases had documented presence in the same room as a patient with MERS.5 Despite the high case-fatality rate , MERS cases can be asymptomatic and mild . Although it is not known how often asymptomatic or mildly symptomatic patients transmit MERS, initiating comprehensive measures such as isolating patients suspected of having or having been exposed to the virus and using personal protective equipment when caring for them may be extremely difficult because so many patients have mild and", "Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome\nPassage: The incidence of MEWDS is unknown. Only small case series are reported in the literature . One of the largest described 34 affected patients reviewed over several years' period . Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome\nPassage: Although MEWDS is suspected to occur as a consequence of a viral-like infection in genetically susceptible individuals, its precise pathogenesis remains unknown. Recovery is gradual, over weeks to months, and the visual prognosis is very favorable . Treatment is usually not required. Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome", "Passage: The aim of the present report was to describe an unusual cluster of seven cases of MEWDS encountered within a 3month period, with an emphasis on the clinical presentation and multimodal imaging findings. The cluster prompted us to seek a common infectious association. Title: Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome\nPassage: A retrospective observational study was conducted in seven patients who presented with MEWDS between July and September 2013 at two tertiary medical centers in central Israel. Data on background, clinical, and laboratory parameters were collected from the medical files. The study was approved by the institutional ethics review board.", "Title: Molecular Phylogeny of Hantaviruses Harbored by Insectivorous Bats in C\u00f4te d\u2019Ivoire and Vietnam\nPassage: Hantaviruses possess a negative-sense, single-stranded, tripartite segmented RNA genome, consisting of large , medium and small segments, encoding an RNA-dependent RNA polymerase , envelope glycoproteins and a nucleocapsid protein, respectively . To date, 23 hantaviruses, hosted by reservoir rodent species, have been recognized as distinct species by the International Committee on Taxonomy of Viruses . Several of these rodent-borne hantaviruses cause acute, febrile diseases of varying clinical severity and lethality in humans, known as hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome . Though once believed to be restricted to rodents , the reservoir host range of hantaviruses is Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus", "Passage: Hantaviruses provide a model system in which to test the dilution effect in directly transmitted zoonoses. Since their initial discovery in the Western Hemisphere in 1982, several dozen hantavirus strains have been found, each hosted by a unique rodent species ; novel hantaviruses have recently been discovered in shrews . Natural hosts are asymptomatic and chronically infected; intraspecies spread is hypothesized to be through bites . Humans become infected with hantavirus by inhaling aerosolized excreta from infected rodents . Occasionally hantavirus pulmonary syndrome develops; this syndrome has a mortality rate of almost 40% and no prophylaxis, treatment, or cure . Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: In recent years, the repeated outbreak of hantavirus disease has caused a serious threat to human health. The spread of hantavirus from natural hosts to humans is a natural ecological process; however, the outbreak of hantavirus is driven by striped field mouse population cycle dynamics and seasonal climate change . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Viral emergence may continue to be promoted as human-introduced changes continue to increase in the environment at different geographical scales. Human incursions into previously uncultivated environments may lead to new contacts between rodent reservoirs and humans, increasing the likelihood of contracting infections . These changes may also alter rodent's population structure and dynamics and interspecies interactions creating conditions that may lead to viral outbreaks, viral establishment in new hosts, and emergence of HCPS , even with seemingly slight ecological disturbance to the virus-host system .", "Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland\nPassage: Although ECoV has been identified on three continents, little is known about the genetic and pathogenic diversity in field viruses. In this study, sequence and phylogenetic analysis demonstrated a high level of homology between viruses detected in a donkey and a horse in two provinces in Ireland in different years. This suggests that Irish ECoVs may have low genetic diversity. Compared with the ECoVs of other countries, the N, S and p12.7 genes of the two Irish viruses were highly conserved. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions . Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: Phylogenetic analysis was performed for the nucleotide sequences of the complete N and partial S genes . The analysis for the N gene showed that Irish ECoVs were independently clustered although they were closely related to Japanese viruses identified after 2009. In the phylogenetic tree of the S gene, Irish ECoVs were closely related to all other ECoVs analysed. Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: The length of the region from the p4.7 to p12.7 genes in the two viruses was 544 base pairs. Compared with NC99, Irish ECoVs, had a total of 37 nucleotide deletions within p4.7 and the non-coding region following the p4.7 gene. Compared with Obihiro 12-1 and 12-2, Irish ECoVs had a three-nucleotide insertion. When compared with Tokachi09, the Irish ECoVs had a 148-nucleotide insertion . The p12.7 gene of the two Irish ECoVs did not have deletions or insertions, and the nucleotide identities were 98.8-99.7% between these viruses and the other ECoVs . Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: of ECoV detection in faeces samples from both foals and adult horses in Ireland. The viruses identified in Ireland are genetically closely related to the Japanese viruses and the results of this study give no indication of significant genetic or phenotypic diversity. In recent years, there has been an increase in awareness and testing for ECoV in the USA and elsewhere . Horse breeding and racing activities in Ireland are the most prominent and important of any country on a per capita basis. There are over 50 Thoroughbred horses per 10,000 of population in Ireland, compared to between three and", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: CDC Summary 21 MAR 2020,", "Passage: More cases of COVID-19 are likely to be identified in the United States in the coming days, including more instances of community spread. CDC expects that widespread transmission of COVID-19 in the United States will occur. In the coming months, most of the U.S. population will be exposed to this virus. Title: CDC Summary 21 MAR 2020,\nPassage: Twenty-seven U.S. states are reporting some community spread of COVID-19. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.", "Title: Early Days of Food and Environmental Virology\nPassage: The evolution of tissue/cell culture was very much a work in progress at this time. Explants had earlier been embedded in plasma clots and maintained with various fluid media while cells migrated outward in a single layer that could be viewed with a microscope. Primary cell cultures were prepared by digesting animal tissue to component cells, using trypsin or other enzymes, often enhanced with versene as a chelator. The cells thus freed were washed and planted in sealed glass vessels in medium typically based on either Hanks' or Earle's balanced salt solution-these had a physiologically balanced content of cations with Title: Early Days of Food and Environmental Virology", "Passage: 16 9 150 mm test tubes and in Leighton tubes, which contained a coverslip near the butt end, on which the cells were grown to provide superior microscopic imaging. Our methods were later described in detail , as well as a machine for changing the medium in the cultures during their outgrowth period . Our research at UC was funded by food industry donations to FRI and a small grant from the US Public Health Service. My application to renew the grant was unsuccessful. Title: Early Days of Food and Environmental Virology\nPassage: Increasingly, in recent times, cultures of tissues other than kidney have given rise to lines that have special applications. And, as will be described later, explant cultures may serve special purposes, where the in vivo organization of the tissue is significant to the investigation. Title: Early Days of Food and Environmental Virology", "Passage: The transition between primary cultures and established cell lines is large. Once animal tissue is broken down and the dispersed cells planted in a culture vessel, some of the cells settle to the glass or plastic surface, attach, spread, and multiply until a confluent monolayer of cells is formed. This is almost entirely fortuitous-the selection of cells that attach to the growing surface and multiply, and why they ideally stop multiplying when the monolayer is complete are beyond the control of the scientist, although the preparation of growing surfaces for this purpose is now well understood. In the case of", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: realtime PCR method was able to detect 6 cases of SARS-CoV positive samples that were not confirmed by any other assay \u2022 The real time PCR has a threshold sensitivity of 10 genome equivalents per reaction and it has a good reproducibility with the inter-assay coefficients of variation of 1.73 to 2.72%. \u2022 13 specimens from 6 patients were positive with viral load range from 362 to 36,240,000 genome equivalents/mL. The real-time RT-PCR reaction was more sensitive than the nested PCR reaction, as the detection limit for the nested PCR reaction was about 10 3 genome equivalents in the standard Title: Low-Cost HIV-1 Diagnosis and Quantification in Dried Blood Spots by Real Time PCR\nPassage: one cycle threshold or so more sensitive than probe-based assays. Title: Low-Cost HIV-1 Diagnosis and Quantification in Dried Blood Spots by Real Time PCR", "Passage: 15 minutes, ramp 20uC/second; 3) Amplification: 50 cycles a) 94uC 10 seconds, ramp 20uC/second, b) 52uC 20 seconds, ramp 20uC/second, and c) 72uC 20 second, ramp 2uC/ second ; 4) Melting: a) 92uC 0 second, ramp 20uC/second, b) 57uC 15 seconds, ramp 20uC/second, and c) 92uC 0 second, ramp 0.1uC/second ; 5) Cooling: 40uC 30 seconds, ramp 20uC/second. Title: Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens\nPassage: a slope = 23.77. The limit of sensitivity was determined in this assay to be 10 viral genome copies/PCR.", "Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: The estimated C. burnetii seroprevalence in the sheep flocks in the area varied from 8% to 24%. The 25% seroprevalence in the flock of the exhibited animals together with a positive polymerase chain reaction in an afterbirth in June 2003 suggested a recent infection of the flock . Seroprevalence among sheep flocks related to human outbreaks tend to be substantially higher than those in flocks not related to human outbreaks. The median seroprevalence in a number of relevant studies performed in the context of human outbreaks , was 40% compared to 1% in sheep flocks not linked to human outbreaks Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3trimester and to test animals in petting zoos regularly for C. burnetii. Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: Serum was collected from all sheep and cows displayed in the farmers' market as well as from all sheep of the respective home flocks . Samples of 25 sheep from five other flocks in the Soest area were also tested for C. burnetii. Tests were performed by ELISA with a phase I and phase II antigen mixture. Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: well as sheep from herds held in the vicinity of Soest were tested for Coxiella burnetii . RESULTS: A total of 299 reported Q fever cases was linked to this outbreak. The mean incubation period was 21 days, with an interquartile range of 16\u201324 days. The case control study identified close proximity to and stopping for at least a few seconds at the sheep's pen as significant risk factors. Vendors within approximately 6 meters of the sheep's pen were at increased risk for disease compared to those located farther away. Wind played no significant role. The clinical attack rate of", "Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA\nPassage: The initiation of sporulation in B. subtilis is subject to complex regulation ). The activation of Spo0A is controlled by a multi-component phosphorelay that can integrate environmental cues and ensures a gradual increase in the level of phosphorylated Spo0A in the cell . In addition, the transcription of the spo0A gene is controlled by multiple feedback loops. For instance, Spo0A regulates its own transcription by binding to the spo0A promoter , as well as by indirectly stimulating the transcription of sigH, encoding a sigma factor that recognizes the spo0A promoter . Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA", "Passage: The initiation of sporulation in B. subtilis is subject to complex regulation ). The activation of Spo0A is controlled by a multi-component phosphorelay that can integrate environmental cues and ensures a gradual increase in the level of phosphorylated Spo0A in the cell . In addition, the transcription of the spo0A gene is controlled by multiple feedback loops. For instance, Spo0A regulates its own transcription by binding to the spo0A promoter , as well as by indirectly stimulating the transcription of sigH, encoding a sigma factor that recognizes the spo0A promoter . Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA", "Passage: Spo0A is the key regulator for sporulation . Most of our knowledge about the protein is based on work in Bacilli. Spo0A is a response regulator that demonstrates phosphorylation dependent binding to DNA . Phosphorylation occurs through the concerted action of several proteins that together form a so called phosphorelay . The signaling cascade allows for the integration of environmental signals into the regulation of Spo0A dependent processes, including sporulation. The two functional domains, the N-terminal phosphorylation and dimerization domain , and the C-terminal DNA binding domain are separated by a hinge region that is relatively poorly conserved . Phosphorylation Title: C. difficile 630\u0394erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA", "Passage: Spo0A is the key regulator for sporulation . Most of our knowledge about the protein is based on work in Bacilli. Spo0A is a response regulator that demonstrates phosphorylation dependent binding to DNA . Phosphorylation occurs through the concerted action of several proteins that together form a so called phosphorelay . The signaling cascade allows for the integration of environmental signals into the regulation of Spo0A dependent processes, including sporulation. The two functional domains, the N-terminal phosphorylation and dimerization domain , and the C-terminal DNA binding domain are separated by a hinge region that is relatively poorly conserved . Phosphorylation", "Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana\nPassage: We administered a face-to-face questionnaire using an adapted WHO and CDC Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. RESULTS: A total 92 HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% could correctly identify the right disinfectant = 28.52, p = Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: A total of 92 HCWs surveyed indicated they were not adequately trained to handle an EVD suspected case. When asked to rate their competence in handling an EVD suspected patient, 18.81% indicated they had little confidence and competence, while 6.93% indicated they were extremely confident to handle a suspected case of EVD . Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana\nPassage: The results of this survey showed that more than half HCWs indicated that their facilities were not ready to handle EVD cases. Nearly 92% indicated they were not adequately trained to handle an EVD suspected case and it is not surprising that less than 50% indicated they would willingly attend to a suspected patient. Moreover, nearly a third of HCWs would also want insurance for themselves and their families in case they were infected with EVD. Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: In estimating the sample size for this study, previous data from the hospital indicates that there are approximately 900 HCWs at the two facilities. Assuming a 95% confidence interval and if 70% of these HCWs would come into contact with an EVD suspected case, allowing an error rate of 10%, approximately 87 HCWs would provide a default study power of 80% and an alpha of 5%. With approximately a non-response rate of 15% allowing us to sample 101 HCWs from the two facilities providing emergency services within the Ashanti Region of Ghana.", "Title: A Global Champion for Health\u2014WHO\u2019s Next?\nPassage: WHO's next Director-General should be a proven leader and advocate, perhaps from a lowincome or middle-income country. The new recruit will be greeted by a full in-tray, and featuring prominently are likely to be the constraints imposed by WHO's current funding mechanisms. A substantial proportion of WHO's existing budget is earmarked for specific projects, leaving the organization with little financial flexibility to respond to unanticipated demands. However, any improved funding mechanism is likely to follow, and be dependent on, organizational reform. According to Kruk, \"WHO is both essential and hamstrung. . .the election of the Director-General should be a moment Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: global body will always be needed to promote, set standards in, and evaluate progress toward better health for people in all countries. The next Director-General will need to heed critics of the organization and craft a process of streamlining and restructuring to produce a new WHO that is demonstrably effective in leading responses to threats to health, and efficient in doing so. As Gostin commented to PLOS Medicine, \"WHO urgently needs a bold reform agenda to fix long-standing problems recognized by every independent group that has evaluated the Organization.\" Political machinations and the enemy within, bureaucracy, are likely to impede Title: A Global Champion for Health\u2014WHO\u2019s Next?", "Passage: for member countries and other funders to reflect on whether they want an implementation agency for their favored health agenda, or an independent institution with the intelligence, agility, and operational capacity to tackle the coming global health challenges.\" Above all, the incoming leader of WHO will need to be open-minded and creative. More than one of the experts we contacted emphasized the fluid nature of the threats to human health to which WHO should shape the world's response. WHO must be able to lead responses in some areas of global health, but, in other areas, working together with more nimble Title: A Global Champion for Health\u2014WHO\u2019s Next?\nPassage: Abstract: In this month\u2019s editorial, the PLOS Medicine Editors propose ideal qualities for the World Health Organization's next Director General, for whom the selection process is now underway.", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The 2019 novel coronavirus , a betacoronavirus, forms a clade within the subgenus sarbecovirus of the Orthocoronavirinae subfamily . The severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus are also betacoronaviruses that are zoonotic in origin and have been linked to potential fatal illness during the outbreaks in 2003 and 2012, respectively . Based on current evidence, pathogenicity for 2019-nCoV is about 3%, which is significantly lower than SARS-CoV and MERS-CoV . However, 2019-nCoV has potentially higher transmissibility than both SARS-CoV and MERS-CoV . Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity . Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Apart from the timely diagnosis of cases, the achievement of favorable clinical outcomes depends on the timely treatment administered. ACE2 has been reported to be the same cell entry receptor used by 2019-nCoV to infect humans as SARS-CoV . Hence, clinical similarity between the two viruses is expected, particularly in severe cases. In addition, most of those who have died from MERS-CoV, SARS-CoV and 2019-nCoV were advance in age and had underlying health conditions such as hypertension, diabetes or cardiovascular disease that compromised their immune systems . Coronaviruses have error-prone RNA-dependent RNA polymerases , which result in frequent mutations and Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Due to the close genetic relatedness of SARS-CoV with 2019-nCoV , there may be potential cross-protective effect of using a safe SARS-CoV vaccine while awaiting the 2019-nCoV vaccine. However, this would require small scale phase-by-phase implementation and close monitoring of vaccinees before any large scale implementation.", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: 1 \u00d7 10 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: factor for HAdV-55 infection in young adults. HAdV-55 DNA was previously reported in 41.2% of patients with severe infection . In our study, HAdV-55 DNA was detected and monitored in all patients with severe ARDS. The initial, and trend of, viral load that presented as HAdV-55 DNA copies in the respiratory tract samples and blood may suggest the severity of infection and may predict both the reaction to therapy and patient outcome. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: factor for HAdV-55 infection in young adults. HAdV-55 DNA was previously reported in 41.2% of patients with severe infection . In our study, HAdV-55 DNA was detected and monitored in all patients with severe ARDS. The initial, and trend of, viral load that presented as HAdV-55 DNA copies in the respiratory tract samples and blood may suggest the severity of infection and may predict both the reaction to therapy and patient outcome. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 \u00d7 10 copies in three patients and was", "Title: Temporal trends in the discovery of human viruses\nPassage: is therefore of considerable interest. Title: Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis\nPassage: addressed. Furthermore, in 2003 a veterinarian died after being infected with bird flu. 16 This focusing event triggered the shift to the fifth stage, during which there were endeavours to increase control over the viral threats. What is remarkable about this shift is that although the virologists occupied different positions and held different views on the science-policy-public nexus, they pushed it through collectively. Title: Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis", "Passage: When SARS struck, the pandemic preparedness plans came into effect. Under the direction of the WHO a small selection of laboratories, including Osterhaus' own lab in Rotterdam, were on the hunt for the cause; and on 16 April 2003 the Osterhaus lab managed to find the final and most rewarding piece of the puzzle. A press meeting was held at the WHO Geneva headquarters that same afternoon; a letter in Nature and a royal decoration followed. Osterhaus reaped the rewards for the discovery and his status rose . But what is more: the WHO prevented a pandemic. This marks the Title: Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis", "Passage: influenza pandemic, scientists and politicians were concerned about the growing threat of bioterrorism and outbreaks of foot and mouth disease. Finally, the outbreak of SARS in 2003 came as a complete surprise. It was SARS that highlighted the real danger of pandemic outbreaks, but that also triggered the awareness of preparedness and prevention plans as new instruments in preventing a pandemic from developing to its full capacity .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: One drawback of an Ad5 vector is the potential for preexisting immunity, so alternative adenovirus serotypes have been explored as vectors, particularly non-human and uncommon human serotypes. Non-human adenovirus vectors include those from non-human primates , dogs, sheep, pigs, cows, birds and others . These vectors can infect a variety of cell types, but are generally attenuated in humans avoiding concerns of preexisting immunity. Swine, NHP and bovine adenoviruses expressing H5 HA antigens have been shown to induce immunity comparable to human rAd5-H5 vaccines . Recombinant, replication-defective adenoviruses from low-prevalence serotypes have also been shown to be efficacious. Low prevalence Title: Virus-Vectored Influenza Virus Vaccines", "Passage: with high preexisting Ad5 antibody titers might have an increased risk of acquiring HIV-1 . Subsequently, the rAd5 vaccine-associated risk was confirmed . While these two instances do not suggest Ad-vector vaccines are unsafe or inefficacious, the umbra cast by the clinical trials notes has affected interest for all adenovirus vaccines, but interest still remains. Title: A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model", "Passage: points. Although not explored in the current study, previous studies have evaluated the impact of pre-existing immunity to PAV3 and the potential reuse of PAV3-based vectors against different pathogens. Groups of outbred pigs with high PAV3 neutralizing antibody titres were vaccinated with a PAV3-based vaccine and vector re-administration did not result in hepatotoxicity or reduced transgene expression . Doses of 10 13 particles/kg AdHu5 vector can also bypass pre-existing immunity, however, several pathologies including liver damage indicated by elevated transaminase, low platelets count, and lymphocytopenia were observed in nonhuman primates administered similar doses . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Despite the many advantages which viral vectoring can offer, pre-existing immunity is a major obstacle of many viralvectored vaccines, such as Ad serotype 5 or herpes simplex virus type 1 , where the rate of seroprevalence to these viruses is very high of the US population, respectively] . Vector-specific antibodies may impede the induction of immune responses to the vaccine-encoded antigens, as they may reduce the dose and time of exposure of the target cells to the vaccinated antigens . In a large-scale clinical trial of an Ad serotype 5 -based HIV-1 vaccine, the vaccines showed a lack of efficacy", "Title: Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and fall/winter waves\nPassage: The confirmed case data is generated by sampling week, which could be different from the week of symptom onset and hence pose a potential source of some bias in data. However, samples were typically taken when the physicians diagnosed and reported H1N1 cases. We refer to 2003 SARS outbreak in Taiwan, when it was estimated that the onset-to-diagnosis interval is 1.20 days for previously quarantined persons and 2.89 days for non-quarantined persons . Given the similarity in symptoms of SARS and influenza as well as the heightened public awareness due to the world-wide alarm over the seriousness of the pH1N1 Title: Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and fall/winter waves", "Passage: program starting in November. The number of cases began to decline by the end of the year, and continued to do so into early next year, until the government announced on February 23 the end of the fall/winter outbreak with over 3000 laboratory-confirmed cases reported, 910 hospitalizations, and 41 deaths . Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: of infection based on clinical cases The wide gap between the two estimates indicates that a large fraction of those who got infected by pH1N1/2009 virus escaped medical detection, probably because they developed mild disease or asymptomatic infection, a further indication of the benign nature of the virus, at least at the community level. In England, Baguelin et al. estimated that the cumulative incidence rates of infection by the pandemic virus in children were 20 to 40 times higher than that estimated from clinical surveillance. Title: Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and fall/winter waves", "Passage: Using routine influenza surveillance data, we modeled the temporal changes of the two waves of pH1N1 epidemic in Taiwan in summer and in fall/winter. The mass H1N1 vaccination program was first initiated sequentially on November 1, where a typical delay of at least two weeks from immunization is needed for protection from the vaccine to take effect in human bodies. Our results suggest that the turning point for the second wave of infections in the fall had occurred around mid-November . Moreover, the class suspension data indicate that the number of class suspensions had peaked by November 20, less than", "Title: Estimating the number of infections and the impact of non-\nPassage: infection-to-death distribution is therefore given by: Title: Estimating the number of infections and the impact of non-\nPassage: coronavirus . Science doi:10.1126/science.abb3221. Title: Estimating the number of infections and the impact of non-\nPassage: to-fight-coronavirus-pandemic . Title: Estimating the number of infections and the impact of non-\nPassage: the increase in daily deaths over the coming week compared to the early stages of the epidemic.", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: In summary, 2019-nCoV is a novel lineage B Betacoronavirus closely related to bat SARS-related coronaviruses. It also has unique genomic features which deserves further investigation to ascertain their roles in viral replication cycle and pathogenesis. More animal sampling to determine its natural animal reservoir and intermediate animal host in the market is important. This will shed light on the evolutionary history of this emerging coronavirus which has jumped into human after the other two zoonotic Betacoroanviruses, SARS-CoV and MERS-CoV. Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats", "Passage: analyses. One unique gene at the 3\u2019 end of the BtCoV/Rh/YN2012 genome, ORF9, exhibits ~30% amino acid identity to ORF7a of the SARS-related coronavirus. Functional analysis showed ORF4a protein can activate IFN-\u03b2 production, whereas ORF3a can regulate NF-\u03baB production. We also screened the spike-mediated virus entry using the spike-pseudotyped retroviruses system, although failed to find any fully permissive cells. Our results expand the knowledge on the genetic diversity of bat coronaviruses. Continuous screening of bat viruses will help us further understand the important role played by bats in coronavirus evolution and transmission. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats", "Passage: geographic isolation and host restrain. Though collected from same province, these three virus strains formed two genotypes correlated to sampling locations. These two genotypes had low genome sequence identity, especially in the S gene and accessory genes. Considering the remote geographic location of the host bat habitat, the host tropism, and the virus diversity, we suppose BtCoV/Rh/YN2012 may have spread in these two provinces with a long history of circulation in their natural reservoir, Rhinolophus bats. With the sequence evidence, we suppose that these viruses are still rapidly evolving.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: induce broader protection than TIV due to the diversity of the immune response consistent with inducing virus-neutralizing serum and mucosal antibodies, as well as broadly reactive T cell responses . While overall both TIV and LAIV are considered safe and effective, there is a recognized need for improved seasonal influenza vaccines . Moreover, improved understanding of immunity to conserved influenza virus antigens has raised the possibility of a universal vaccine, and these universal antigens will likely require novel vaccines for effective delivery . Title: Current and Novel Approaches in Influenza Management", "Passage: LAIV viruses in the nasopharynx elicit immune response that epitomizes a natural influenza infection. For this reason, LAIV has shown some superiority over the IIV in terms of the induction of mucosal immunity via secreted immunoglobulin A . Use of the LAIV has proven to be safe in children and immunocompromised persons . The most spelt-out advantage is the \"non-invasive\" capacity of the attenuated viruses and this had made it suitable to use for all categories of vaccines, although LAIVs are not recommended for people with underlying chronic medical conditions . A typical setback to the use of the LAIV Title: Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes", "Passage: simulated vaccine matches varied by season and decreased with age . Recent post-licensure effectiveness studies comparing the effectiveness between LAIV and the inactivated influenza vaccine found equivocal results , while a clustered randomized trial found no difference between LAIV and inactivated influenza vaccine on a community level . Therefore, we assumed a similar effectiveness of Q-LAIV and TIV. As the vaccine effectiveness of TIV wanes already within the season, we assumed its duration of protection to last 1 year. No long-term effectiveness data is available for Q-LAIV, but a clinical trial in young children suggests that the vaccine could provide Title: Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes", "Passage: We took the duration of protection of influenza vaccination as one season, while some evidence suggests that LAIV may provide longer protection . However, our sensitivity analysis demonstrated that a longer duration of protection of Q-LAIV would slightly increase the average impact of the vaccination program, but not mitigate the increased variability in epidemic size. Similar results were obtained for the model that focused on influenza A/H3N2 . A longer duration of protection by Q-LAIV does not affect the increase in variability in epidemic size because vaccinated children will also be vaccinated in the next season ; only children that", "Title: Genome Sequences of Porcine Epidemic Diarrhea Virus: In Vivo and In Vitro Phenotypes\nPassage: PEDV is a member of the Coronavirinae subfamily and belongs to the Alphacoronavirus genus. Its genomic size ranges from approximately 26 to 32 kb, which is relatively large for an RNA virus. Although vaccines for PEDV exist in China, Japan, and South Korea, there is no approved vaccine in the United States or Europe . Furthermore, PEDV is still evolving within the U.S. swine population. Title: Genome Sequences of Porcine Epidemic Diarrhea Virus: In Vivo and In Vitro Phenotypes", "Passage: The whole-genome sequences of NPL-PEDV/2013 and NPL-PEDV/2013/P10 contain 28,038 and 28,025 nucleotides , respectively, including the 5= and 3= untranslated regions . The NPL-PEDV/2013 genome shares 99% identity with all the U.S. isolates sequenced to date and many Chinese isolates as well. The top three BLAST hits were against U.S. isolates, USA/Colora-do/2013 , IA1 , and an isolate from Iowa, 13-019349 . The NPL-PEDV/2013 isolate also shares 99% identity with the Chinese outbreak isolate AH2012 . Title: Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan", "Passage: The PEDV genome is comprised of at least seven open reading frames encoding four structural , envelope , membrane , and nucleocapsid proteins . A high degree of genetic diversity has been observed in the S glycoprotein gene . Partial spike polyprotein genes located in the virus envelope are central to PEDV biological properties such as interactions with cellular receptors during virus entry, the neutralizing of antibody induction in natural hosts, growth adaptation in vitro, and virulence attenuation in vivo . The PEDV spike protein is a type 1 transmembrane envelope glycoprotein with a 4,158 nucleotide sequence divided into S1 Title: Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses", "Passage: to severe diarrhea, shed high quantities of PEDV in feces ranging from 3.96 x 10 10 to 7.57 x 10 10 (RNA copies/ml, , and had histopathological lesions of moderate to marked atrophic enteritis compatible with PEDV infection. The negative control pig showed no clinical signs, tested negative by PCR and had normal intestinal histomorphology.", "Title: Mode and tempo of human hepatitis virus evolution\nPassage: HCV is, however, genetically heterogeneous and the epidemic subtypes represent a minor fraction of viral diversity. Eight major HCV genotypes have been described, and these are further divided into at least 90 subtypes . Several of these genotypes and subtypes were identified and classified only recently , suggesting that a considerable proportion of HCV diversity remains undescribed. Moreover, a number of natural inter-genotype recombinants were reported was generated using PhyML . Hepatovirus host silhouettes are colored according to taxonomic order. The human HAV subgenotypes are also reported. Title: Spread of different rhinovirus B genotypes in hospitalized children in Spain", "Passage: The description of new genotypes is an evolving process. In this sense, apart from 33 types initially defined within HRV-C, 4 up to 18 new types have been recently accepted, and 12 more are awaiting approval. With regard to HRV-A, serotypes 101, 102, and 103 have been recently accepted . Up to date, only one new genotype has been defined within HRV-B, the strain CU211, described in Thailand. 5 The definition of new genetic types is based on the nucleotide sequence divergence defined as the pairwise distance between sequences. According to the analysis of Wisdom et al. 6 and Simmonds Title: Mode and tempo of human hepatitis virus evolution", "Passage: For a long time, it was thought that hepatoviruses were restricted to humans and non-human primates , with genetically distinct variants classified as six main different genotypes : three isolated from humans and subclassified in 6 subgenotypes and three of simian origin . However, despite genetic heterogeneity, HAV viruses belong to a single common serotype. Title: Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/K(b) Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: To ensure the sample size in some statistical analyses, we combined the patients according to the disease severity into mild/moderate and severe/critical groups for comparison. In this case, the number of patients with a severity degree of mild/moderate and severe/critical was 22 and 23, respectively. According to the clinical observation, the illness could be divided into the acute phase and the convalescent phase .", "Title: Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model\nPassage: In order to test the predictions made in the previous section by applying the mathematical model to parallel plaque and viral yield assays, we performed two additional experimental tests which could provide some qualitative and quantitative confirmation. Title: Testing Modeling Assumptions in the West Africa Ebola Outbreak\nPassage: model. However, we believe that newer data will confirm our initial conclusions. Title: Point\u2010of\u2010care testing in primary care: A systematic review on implementation aspects addressed in test evaluations\nPassage: 1. The study design, classified according to one of three categories; namely, empirical study , qualitative study or modelling study. Title: Avian influenza A/H7N9 risk perception, information trust and adoption of protective behaviours among poultry farmers in Jiangsu Province, China", "Passage: The conceptual model was tested using structural equation modelling with demographic variables entered into the model as observed covariant variables and PMT constructs entered as latent variables. All covariance, factor loadings, measurement errors, disturbances and path coefficients were estimated using robust maximum likelihood estimator . Path coefficients with p-values less than 0.05 were considered as statistically significant. Multiple model fit indices including CFI, TLI, RMSEA and SRMR was used to assess the global model fit. Values of CFI and TLI great than 0.9, of RMSEA and SRMR less than 0.8 suggest an acceptable fit of the model to data. The", "Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus\nPassage: easy-to- use system . Our reBmBac system has two major improvements relative to this system. First, the fragment replaced during homologous recombination in our reBmBac system is only a 1.2 kb tet R gene. In contrast, the fragment in bBpGOZA is more than 6 kb, and it contains a miniF replicon and a kan R gene. Second, the CopyControl origin in our system facilitates the large-scale preparation of high-quality reBmBac DNA. Our results over the course of many experiments indicated that the high quality of reBmBac DNA and transfer plasmid DNA are key factors for achieving good recombination results. We Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Similarly, recombinant antibodies have several advantages: bacteria, yeast, plants, or animals can be used to produce antibodies, no need for immunization, and intrinsic properties can be modified easily using mutagenesis techniques. Genetically engineered antibodies have integral characteristics that suit various downstream applications or can be converted into functional whole immunoglobulins . Antibodies exhibit strong immunity to defend against foreign antigens and non-selfagents. However, a variety of recombinant antibodies is needed to interact these hostile antigens. Over the last decade, the use of antibody engineering or recombinant antibody technology has shaped the genetic manipulation of a diverse range of antibody fragments Title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA", "Passage: Manipulation of BACs using traditional cloning procedures can be difficult and thus a range of methodologies that apply bacterial genetics, including homologous recombination within the E. coli host, have been developed ). The use of homologous recombination allows site-directed mutagenesis of BACs and, by employing a counterselection scheme, specific modifications can be obtained without leaving residual \"foreign\" sequences . The main advantage of this method is that there are no target limitations and no need for suitable restriction sites. The integration of the modified sequence is performed in vivo thereby potentially being more accurate than in vitro approaches like PCR-based Title: A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus", "Passage: A novel defective-rescue reBmBac expression system was successfully developed. The examples of luciferase and PoIFN-\u03b3 expression showed that foreign genes can be successfully expressed with this system. These results show that the novel reBmBac silkworm expression system is excellent and has the following advantages: This system allows for simple and rapid generation of recombinant BmNPVs carrying foreign genes. Because the defective ORF1629 and the introduction of the CopyControl origin of replication, the purity of the recombinant virus harvested during cotransfection approaches 100%. The luciferase expression level could be used as the quality control for the cotransfection and expression efficiency of", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: of movement restriction that was in place from 5 February onwards. Figure 1 shows the epidemic curve by contact history and type of membership. The highest incidence of illness onset was observed on 7 February. The epidemic curve in a latter half period was dominated by crew members whose movement was not strictly controlled due to the need to continue service on the ship. The second dominating group was passengers with close contact history. The last illness onset date on board of a passenger without close contact was on 14 February. Estimating the incidence of infection, the peak incidence was Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 and 766 cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: identified for the period from 2 to 4 February among passengers both with and without close contact . The incidence of infection abruptly dropped after 5 February, the date of movement restriction. Among passengers without close contact, the incidence was estimated to be zero, except for 8-10 February 2020, during which 0.98 persons : 0, 7.74) per day were estimated to have been infected. The epidemic peak among crew members was seen for the period from 8 to 10 February 2020. Figure 3 compares the cumulative incidence with and without movement restriction policy from 5 February. In the presence of", "Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: We will develop and apply novel modelling approaches to the analysis of the household infection data to estimate specific transmission parameters, building on previous research . Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: it might be worth considering how the proposed proximity data might relate to existing diary-based studies. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: We will investigate the predictors of influenza infection and the factors affecting duration of symptoms. We will further examine the effect of environmental and lifestyle factors, and measures of risk perception on the disease course and onward transmission using regression models. We will examine the factors affecting adherence to interventions using regression models. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: We will further investigate the intervention effects for influenza A and influenza B separately, although with likely lower incidence the statistical power for the latter may be low.", "Title: Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation\nPassage: The complex mechanisms driving the pathogenesis of autoimmune diseases remain poorly understood. The drugs currently in clinical use cannot effectively eliminate autoimmune diseases and may cause side effects. In recent years, an increasing number of studies have shown that innate immune disorders are closely related to autoimmune diseases . The pattern recognition receptors of the innate immune system are able to recognize pathogen-associated molecular patterns , which trigger relevant signal transmission leading to inflammatory responses. Unfortunately, excessive inflammation can induce autoimmune diseases, such as psoriasis, systemic lupus erythematosus, and rheumatoid arthritis . Therefore, identification of new therapeutic targets to ameliorate Title: Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis", "Passage: the increased production of proinflammatory cytokines, which lead to the aberrant activation of Th1 and Th17 proinflammatory responses. Activated encephalitogenic adaptive immune effectors express surface molecules that allow them to penetrate the blood-brain barrier and to enter the central nervous system . The presence of autoreactive immune effectors, together with abnormally activated CNS astrocytes and microglia, leads to the increased production of reactive oxygen species, excitotoxicity, autoantibody production, and direct cytotoxicity, which are all involved in the demyelination and axonal and neuronal damage that is present in patients with MS. Potential therapeutic interventions at different levels of the immunopathological cascade Title: Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis", "Passage: of S1pr in a murine model . The immunomodulatory effect of fingolimod acts in two pathways. In one pathway, it inhibits the function of S1PR, which facilitates the CC-chemokine receptor 7- mediated retention of lymphocytes in the lymph nodes, including na\u00efve T cells and central memory T cells, but not effective memory T cells. This significantly reduces the infiltration of inflammatory cells into the CNS and reduces the numbers of autoreactive Th17 cells that are recirculating via the lymph and blood to the CNS . The second pathway prohibits neuroinflammation via the modulation of the . This activation results in Title: Negative Immunomodulatory Effects of Type 2 Porcine Reproductive and Respiratory Syndrome Virus-Induced Interleukin-1 Receptor Antagonist on Porcine Innate and Adaptive Immune Functions\nPassage: Scientific .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: HCPS, a disadvantageous consequence of the close anatomic juxtaposition of the two organs. Thus, at least three classes of potential mechanisms, some overlapping and all certainly nonexclusive of the others, could be presumed to underlie the pathogenesis of HCPS. These include: Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: severe forms of HFRS and HCPS have begun to achieve sufficient mass as to induce, through PAMP-PRR interactions and other means, the expression of proinflammatory cytokines . For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed, and yet it is often not appreciated that the expected preferential tissue tropism of HFRS-associated viruses and their HCPS-associated counterparts for the renal and pulmonary beds, respectively, is not as one would predict through the manifestations of the two diseases. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: By the time symptoms appear in HCPS, both strong antiviral responses, and, for the more virulent viral genotypes, viral RNA can be detected in blood plasma or nucleated blood cells respectively . At least three studies have correlated plasma viral RNA with disease severity for HCPS and HFRS, suggesting that the replication of the virus plays an ongoing and real-time role in viral pathogenesis . Several hallmark pathologic changes have been identified that occur in both HFRS and HCPS. A critical feature of both is a transient capillary leak involving the kidney and retroperitoneal space in HFRS and the lungs Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: Increased capillary leakage due to hantaviral infection is the basic pathogenic feature for both HFRS and HCPS. Therefore, treatment strategies improving microvascular endothelial cell function seem to be feasible in mitigating disease severity and reducing mortality . Hantavirus-disturbed vascular function is a multifactorial event whose complicated mechanisms still need to be elucidated, and two kinds of hypothesis have been developed. The vascular endothelial growth factor theory was first proposed and studied in depth. VEGF binding to VEGF receptor 2 could activate SFK signaling, which may result in dissociation, internalization, and degradation of VEcadherin. Altered expression and localization of VE-cadherin contributed", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Like SARS-CoV, 2019-nCoV induced pneumonia through respiratory tract by clinical observation. Therefore, the presence of viral antigen in oral swabs was used as detection standard for 2019-nCoV. Similarly, two times of oral swabs negative in a 24-h interval was considered as viral clearance by patients officially. Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: swabs were only taken when patients were symptomatic. Previously, virus isolation has been the gold standard for infl uenza detection but RT-PCR is now considered to be more sensitive and specifi c. A previous study by some of the current authors has shown that seroconversion occurs in 80%-90% of serum samples if they are tested a suffi cient time after infection . Nasal swabs are a relatively peripheral type of sample . If viral load is low in the nose, the sample may be insuffi cient as an antigenic stimulus to induce a detectable level of seroconversion in the serum. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: In the first investigation, we aimed to test whether viral positive can be found in anal swab and blood as well as oral swabs. We conducted a molecular investigation to patients in Wuhan pulmonary hospital, who were detected as oral swabs positive for 2019-nCoV upon admission. We collected blood, oral swabs and anal swabs for 2019-nCoV qPCR test using previously established method . Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: through routine surveillance, and thus pose a threat to other people. In contrast, we found viral antibodies in near all patients, indicating serology should be considered for 2019-nCoV epidemiology. A possible shift from oral positive during early infection to anal swab positive during late infection can be observed. This observation implied that we cannot discharge a patient purely based on oral swabs negative, who may still shed the virus by oral-fecal route. Above all, we strongly suggest using viral IgM and IgG serological test to confirm an infection, considering the unreliable results from oral swabs detection.", "Title: Epidemiological and clinical profile of Korean travelers receiving international medical repatriation\nPassage: 2 of those transported via ship exhibited pain responses only and 2 of those transported via air ambulance were unresponsive . Conservative management in intensive care units was provided for 8 stretcher patients, 4 air ambulance patients, and 1 ship patient; 5 patients who used prestige accommodation were treated with ward procedures only. The need for a ventilator was the most common reason for use of an air ambulance . In terms of hospitalization duration, 9 stretcher patients, 3 of those using prestige accommodations, 2 traveling by ship, and 4 transporting via air ambulance patients had hospital stays of 1 Title: Long-term respiratory follow-up of H1N1 infection\nPassage: were patients that admitted in our hospital for the first time. Title: Clinical characteristics of pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Northern Bavaria, Germany", "Passage: Patients admitted to an intensive care unit ICU treatment was reported for six of the 94 patients. Four of them had known underlying chronic diseases or predisposing factors: i) A two-month-old former preterm with congenital heart defect was admitted due to desaturation and pneumonia. After treatment with oxygen and antibiotics, he was discharged after three days on PICU and 31 days in hospital. ii) A ten-year-old boy with chronic neurologic and lung diseases was treated at PICU for one day due to fever convulsion. iii) A ten-year-old boy with tuberous sclerosis as chronic disease was admitted to PICU due to Title: Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children\u2019s Hospital, Cape Town, South Africa in 2011", "Passage: Limitations of study include an incomplete epidemiological analysis of study patients to account for patient movements within the hospital. The epidemiological observations excluded five of the 14 RXH patients of which two were potential HAIs. Patients 1.1 c and 2.1 b developed infection symptoms within the RXH ICU at nine and 17 days post hospital admission, respectively. Influenza PCR-based testing was unable to determine whether they acquired the infection within this ward. However, access to this information would not have aided our ability to establish virus transmission linkage. Furthermore, the identification of HAI sources may ultimately require exhaustive longitudinal sampling", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: In summary, 2019-nCoV is a novel lineage B Betacoronavirus closely related to bat SARS-related coronaviruses. It also has unique genomic features which deserves further investigation to ascertain their roles in viral replication cycle and pathogenesis. More animal sampling to determine its natural animal reservoir and intermediate animal host in the market is important. This will shed light on the evolutionary history of this emerging coronavirus which has jumped into human after the other two zoonotic Betacoroanviruses, SARS-CoV and MERS-CoV. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans", "Passage: Bat-borne zoonotic viruses have been responsible for several important emerging zoonotic infectious disease outbreaks in the last two decades including Hendra virus, Nipah virus, Ebola virus, SARS and MERS coronaviruses . It is important to note that, almost in all of the cases, an intermediate host has been identified to play a crucial role in amplifying and transmitting the virus from bats to humans such as horses for Hendra virus, pigs for Nipah virus and palm civets for SARS-CoV . With multiple reports of PRV presence in bats in many parts of Asia and a higher than expected prevalence in Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats", "Passage: Text: Members of the Coronaviridae family are enveloped, non-segmented, positive-strand RNA viruses with genome sizes ranging from 26-32 kb . These viruses are classified into two subfamilies: Letovirinae, which contains the only genus: Alphaletovirus; and Orthocoronavirinae , which consists of alpha, beta, gamma, and deltacoronaviruses . Alpha and betacoronaviruses mainly infect mammals and cause human and animal diseases. Gamma-and delta-CoVs mainly infect birds, but some can also infect mammals . Six human CoVs are known to cause human diseases. HCoV-HKU1, HCoV-OC43, HCoV-229E, and HCoV-NL63 commonly cause mild respiratory illness or asymptomatic infection; however, severe acute respiratory syndrome coronavirus and", "Title: Building Cell Selectivity into CPP-Mediated Strategies\nPassage: and cellular cytotoxicity in a variety of tumor cell lines. Furthermore, direct injection of P15-Tat into C57BL6 mice bearing day 7-established solid tumors resulted in substantial regression of the tumor mass . Title: In-Vitro Subtype-Specific Modulation of HIV-1 Trans-Activator of Transcription (Tat) on RNAi Silencing Suppressor Activity and Cell Death", "Passage: Additionally, to understand whether Tat subtypes use the same mitochondria-dependent pathway to cause cell death, we measured levels of cell death induced by two different genetic subtypes that could be co-related with the release of cytochrome C . Under identical conditions, we observed a 2-3-fold increase in release of cytochrome-C with subtype-B Tat as compared to that of subtype-C Tat . As expected, the untreated control Jurkat T-cells showed no cytoplasmic release of cytochrome-C. Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: The Vero E6 cell line, derived by immortalization of African Green monkey kidney cells, is the most commonly used cell line for testing antivirals against filoviruses. EBOV propagates very well in this cell line, and many laboratories, including ours, generate their virus stocks and determine virus titers in Vero E6 cells. However, the argument to use a cell line with more relevance to human disease has come up repeatedly. Hence, the human liver cancer cell line, Huh 7 and human MDMs were chosen for these studies. Macrophages are relevant to human disease, and they are considered to play an important Title: In-Vitro Subtype-Specific Modulation of HIV-1 Trans-Activator of Transcription (Tat) on RNAi Silencing Suppressor Activity and Cell Death", "Passage: Similarly, cell death induced by Tat variants and subtypes was measured on TZM-bl cells by PI staining followed by flow-cytometry with the empty pCMV-Myc vector was used as a control. Once again, it was confirmed that TatB exhibited higher level of 50% than TatC which resulted in 25% of cell death. TatN12 showed 23% of cell death which was relatively similar level to TatC. TatD60 and TatVT6 exhibited 32% and 36% of cell death respectively which was higher than TatC and the data was normalized with the protein expression of corresponding Tat subtypes and variants indicating differential cell death .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November. Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In the region of Ar Riyad, including the capital city of Riyadh, a hospital based cluster began, within a single hospital, from late June 2015 . By mid-September there had been approximately170 cases reported but the outbreak appeared to been brought under control in November. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Fig. 3 Monthly detections of MERS-CoV and of cases who died with some dates of interest marked for 2012 to 4 th September 2015. An approximation of when DC calving season and when recently born DCs are weaned is indicated. Spring and summer in the Arabian Peninsula are also shaded. Note the left-hand y-axis scale for 2014 and 2015 which is greater than for 2012/13. Sources of these public data include the WHO, Ministries of Health and FluTrackers . Earlier and subsequent versions of this chart are maintained on a personal blog . Modified and reprinted from Mackay IM, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In Jeddah between March and July 2014 , there was a rapid increase in MERS cases, accompanied by intense screening; approximately 5,000 samples from in and around the region were tested in a month yielding around 140 MERS-CoV detections . Among 5,065 individuals sampled and tested across the KSA between October 2012 and September 2013,108 detections were made in a hospital-centric population which included hospitalized cases , their families and associated HCWs . Among the detections, 19 were HCWs and 10 were family contacts .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Thus, the unique physicochemical properties of the phage, in combination with modular display of peptides and proteins with known binding specificity, have spawned wholly novel materials with diverse applications. It is worth noting that the unusual biophysical properties of the filamentous phage can also be exploited in the study of structures of other macromolecules. Magnetic alignment of high-concentration filamentous phage in solution can partially order DNA, RNA, proteins, and other biomolecules for measurement of dipolar coupling interactions in NMR spectroscopy. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Thus, the unique physicochemical properties of the phage, in combination with modular display of peptides and proteins with known binding specificity, have spawned wholly novel materials with diverse applications. It is worth noting that the unusual biophysical properties of the filamentous phage can also be exploited in the study of structures of other macromolecules. Magnetic alignment of high-concentration filamentous phage in solution can partially order DNA, RNA, proteins, and other biomolecules for measurement of dipolar coupling interactions in NMR spectroscopy.", "Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic\nPassage: Are there unidentified genetic, host, or environmental susceptibility factors that drive influenza disease severity and copathogenicity? It is important to answer this question in designing universal vaccines, not the least because the most important goal of such vaccines is not to prevent influenza, but to prevent influenza deaths. Another challenging problem is recent controversial evidence from population studies in Canada and elsewhere suggesting that sequential influenza immunization can, in some situations, cause an increased risk of subsequent wild virus infection . In attempting to understand these data, scientists have begun to examine complex immunological phenomenon such as \"original antigenic sin\" Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: However, we have no assurance that other HAs and NAs do not pose as great a threat , requiring that truly universal influenza A vaccines protect against viruses possessing all 25 of these highly different surface glycoproteins , each expressing multiple and unique critical epitopes. This represents an extraordinarily steep challenge to vaccine development, but it is only a part of the total threat that universal vaccines must face. Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: What are the implications of these many potential forms of IAV emergence for universal influenza vaccine prevention? Clearly, influenza has displayed an array of deadly mechanisms for host switch, evolution, and escape from population immunity. How many additional mechanisms are we completely unaware of, and what sorts of vaccines could be produced to prevent emergences in humans of novel IAVs introduced by any such mechanism? To make universal vaccines, we need to understand and synthesize an enormous amount of virologic, pathologic, immunologic, epidemiologic, and historical information about many, diverse, and ever-changing influenza viruses. Title: Computational Approaches and Challenges to Developing Universal Influenza Vaccines", "Passage: In the history of fighting infectious diseases, vaccinations are amongst the most cost-effective approaches available to prevent infection. Traditional approaches to vaccine design have been successful against many pathogens. But vaccines that target rapidly-evolving and genetically-diverse disease agents have frequently failed to generate long lasting protection for human populations. This is particularly true for influenza viruses, a single-stranded, negative sense RNA virus. One of the important weapons being developed to effectively prevent influenza virus infection is a vaccine that can provide durable and broadly-reactive protection against multiple subtypes, including those that may cause potential pandemics, that is, a universal influenza", "Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults\nPassage: to be the most common species among adults, as has been reported elsewhere. 8, 9, 11, 12, 14 HCoV-OC43 and HCoV-229E were the most common strains in alternate seasons, reflecting a season-to-season variability of HCoV strain circulation that has been reported in other multiyear studies. 4 8 The mechanisms by which this particular species elicits these symptoms are not known. Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: The findings of our study, conducted over a 5-year period at five geographically dispersed sites in the USA, demonstrate that human coronavirus is an important cause of influenza-like illness ranged from 4% to 22%. 14 Additionally, we found HCoV-OC43 Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: Abstract: Human coronavirus is a known cause of influenza\u2010like illness . In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR\u2010positive for HCoV. The distribution of species was as follows: HCoV\u2010OC43 , HCoV\u2010229E , HCoV\u2010NL63 , and HCoV\u2010HKU1 . We did not observe species\u2010specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV\u2010HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness. Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820427/", "Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America\nPassage: A clinical attack rate below 1.4% due to pH1N1 has been estimated for the spring of 2009 in the US , a clinical attack rate of 7.5% has been estimated in New Zealand for the entire influenza season between April and August 2009 and in England the estimated clinical attack rate was 10 times lower than the cumulative incidence of infection of 20% suggested from serosurveys of 15-24 year olds . We suggest that a relatively low clinical attack rate -but a much higher infection rate -by a virus causing generally mild disease would allow community transmission of the virus Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1", "Passage: Estimates of the attack rate for Influenza vary greatly. In the authors report an attack rate of 68% among servicemen during an H1N1 outbreak in Finland during the winter of 1977-78. Among the 1575 surveyed in La Gloria an attack rate of 39% was observed. Finally, a recent report in Peru indicates that 33% of cases were asymptomatic, meaning that the attack rate in La Gloria could actually be as high as 58% if we Figure 2 Simulation results for the estimate of the mean of the serial interval. The first boxplot in each frame shows results when all the Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: Overall, we found that 17.7% of participants had serologic evidence of pandemic 2009 virus infection after the peak of the outbreak. This proportion refl ects the observed 16% seroprevalence in adults in Melbourne . These rates are lower, however, than the 31.7% antibody positivity found in South Australia during a prelicensure study of pandemic infl uenza vaccine in July 2009, which excluded subjects with confi rmed or suspected pandemic 2009 infl uenza . This difference in titers may have refl ected geographic differences in infection rates or differences between the populations sampled. Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season", "Passage: Data on clinical presentation was available for 42 of the 65 fatalities during the pandemic seasons and for 28 of the 38 during the 2010-2011 season . In both seasons, fatal cases presented mainly with respiratory symptoms , including acute respiratory distress syndrome , followed by systemic symptoms .", "Title: Estimating the number of infections and the impact of non-\nPassage: Norway 0.41% Title: Estimating the number of infections and the impact of non-\nPassage: and Norway, reflecting the relative stages of the epidemics. Title: Estimating the number of infections and the impact of non-\nPassage: Norway measures cough or fever symptoms.44 15/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: 23.000 kan vaere smittet. NRK https://www.nrk.no/norge/folkehelseinstituttet-mener-23.000-kan-", "Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen\nPassage: specialized cell types including osteoclasts and renal epithelial cells, v-ATPases can also be expressed on the plasma membrane, where they pump protons into the extracellular space . In cancer cells v-ATPases are expressed on the plasma membrane in order to eliminate toxic cytosolic H + . Most importantly, v-ATPases contribute to the acidic tumor microenvironment, which leads to the activation of proteases, thus facilitating tumor cell migration, invasion and angiogenesis . Since the inhibition of v-ATPase was shown to reduce the invasiveness of cancer cells and metastasis formation , this enzyme has emerged as a promising drug target in the Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: cell types including osteoclasts and renal epithelial cells, v-ATPases can also be expressed on the plasma membrane, where they pump protons into the extracellular space . In cancer cells v-ATPases are expressed on the plasma membrane in order to eliminate toxic cytosolic H + . Most importantly, v-ATPases contribute to the acidic tumor microenvironment, which leads to the activation of proteases, thus facilitating tumor cell migration, invasion and angiogenesis . Since the inhibition of v-ATPase was shown to reduce the invasiveness of cancer cells and metastasis formation , this enzyme has emerged as a promising drug target in the recent Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: The vacuolar-type H + -ATPase is the major proton pump responsible for acidification of intracellular compartments in eukaryotic cells . The enzyme consists of two multi-subunit complexes, the soluble V 1 transmembrane V o subcomplex required for the proton transport across membranes . In most cell types v-ATPases are only expressed in the endomembrane system to regulate and maintain the acidic pH of intracellular compartments such as lysosomes, endosomes, the Golgi apparatus, secretory granules and coated vesicles . The function of v-ATPases is essential for cellular processes such as vesicular trafficking, receptor-mediated endocytosis and protein degradation and processing. In specialized Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: Text: The vacuolar-type H + -ATPase is the major proton pump responsible for acidification of intracellular compartments in eukaryotic cells . The enzyme consists of two multi-subunit complexes, the soluble V 1 transmembrane V o subcomplex required for the proton transport across membranes . In most cell types v-ATPases are only expressed in the endomembrane system to regulate and maintain the acidic pH of intracellular compartments such as lysosomes, endosomes, the Golgi apparatus, secretory granules and coated vesicles . The function of v-ATPases is essential for cellular processes such as vesicular trafficking, receptor-mediated endocytosis and protein degradation and processing. In", "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: Data on viral shedding dynamics could help in assessing duration of infectiousness. For severe acute respiratory syndrome-related coronavirus , infectivity peaked at around 10 days after illness onset , consistent with the peak in viral load at around that time . This allowed control of the SARS epidemic through prompt detection of cases and strict isolation. For influenza virus infections, virus shedding is highest on the day of illness onset and relatively higher from shortly before symptom onset until a few days after onset . To date, transmission patterns of 2019-nCoV appear more similar to influenza, with contagiousness occurring around Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: are known to appear soon after the onset of virus shedding. Title: Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews\nPassage: Infected animals caught in 2013 received an intensive initial health monitoring including shedding of the virus for 4 weeks. In these three naturally infected shrews , viral RNA was present in saliva, lacrimal fluid, skin swabs, urine and faeces as well as in the ground substrate from their lairs . During the observation period viral RNA was consistently present in swabs from saliva and skin, however detection varied in urine, lacrimal fluid and was solely sporadically possible in faeces. Ct-values were lowest in samples of saliva. Title: Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews", "Passage: Interestingly, shedding of viral RNA was continuously present.As shrews were naturally infected before trapping, the time between the infection and first virus release remain unknown. However, low ct-values were found in samples taken at time points at least more than 4 to 8 weeks after infection and at time points at least more than 200 days after infection. This indicates a persistent BoDV-1 infection as known from other animals with long lasting and continuous virus release. There was certain variability in the amount of viral RNA, sites of shedding, between individual animals and for the time points of sampling. Some", "Title: Sentinel surveillance for human enterovirus 71 in Sarawak, Malaysia: lessons from the first 7 years\nPassage: An analysis of the proportion of the different types of specimens and the virus yield obtained is shown in Table 2 . More than 2000 specimens from outbreak and nonoutbreak periods were tested from 1998 to 2005. Enteroviruses were grown from 21.6% of those tested. Throat swabs comprised 72.3% of the total number of specimens tested and 25.4% of these yielded enteroviruses. Detailed information about the enterovirus serotypes isolated during this surveillance programme is also provided . Although on the whole, the virus isolation success rate was much lower than anticipated from the results for the first 18 months, it Title: Sentinel surveillance for human enterovirus 71 in Sarawak, Malaysia: lessons from the first 7 years", "Passage: A detailed analysis was done on data collected from two sentinel clinics, coded S1 and S2, which had sent samples to our laboratory consistently and reliably throughout the seven-year study period. A total of 2570 specimens were collected from 1894 cases during the 7 years. Of the 1894 cases, specimens from 1804 were subjected to virus isolation. A total of 2272 specimens were subjected to virus isolation, thus ensuring that the majority of specimens from the majority of cases were tested . Title: Sentinel surveillance for human enterovirus 71 in Sarawak, Malaysia: lessons from the first 7 years", "Passage: All specimens received were subjected to virus isolation. Fifty specimens from 44 children, of a total of 579 specimens, were too heavily contaminated with bacteria. Twenty four of the contaminated specimens were rectal swabs, 19 were throat swabs and 7 were from various skin lesions. All remaining uncontaminated cell culture harvests were tested for enteroviruses by using the pan-EV set of primers and 235 of the 529 specimens tested yielded an enterovirus, but only 15 of the 235 enteroviruses were HEV71. These specimens were from 259 children and an enterovirus was isolated from 153 children. Only 6 of the children Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case", "Passage: After informed consent was obtained, the cadaver was stored at 4uC and underwent autopsy about 18 h after death. The autopsies were done following conventional protocols with strict adherence to biosafety procedures . Twenty-four tissues were collected from respiratory, digestive, nervous, urinary and lymphatic organ systems. Duplicate tissue samples were collected; one sample was fixed in diethylpyrocarbonate treated 10% formalin for pathologic analyses, while a second sample was frozen at 280uC for virus isolation and molecular analyses.", "Title: Timeliness of contact tracing among flight passengers for influenza A/H1N1 2009\nPassage: Our study shows that the longest delay before identification of contact details for an influenza index case is caused by the time between arrival and laboratory diagnosis . This delay is a result of patients delay in seeking medical care, and doctor's delay, including laboratory confirmation. For influenza, the indicated laboratory test was Polymerase Chain Reaction, which takes several hours to obtain the result and in the beginning of the pandemic, the PCR test was not yet available in many laboratories. Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: because cases currently being detected and reported would have mostly been infected in mid- to late-January. Average delays between infection and illness onset have been estimated at around 5\u20136 days, with an upper limit of around 11-14 days , and delays from illness onset to laboratory confirmation added a further 10 days on average . Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: cases currently being detected and reported would have mostly been infected in mid-to late-January. Average delays between infection and illness onset have been estimated at around 5-6 days, with an upper limit of around 11-14 days , and delays from illness onset to laboratory confirmation added a further 10 days on average . Title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling", "Passage: after onset of symptoms for both RT-PCR and culture procedures. For most laboratory tests, specimen procurement within 72 hours of from the onset of symptoms is recommended , yet patients often present much later in the course of illness. Estimates of the median time since onset of symptoms suggest a delay of 3 and 5 days for outpatient and inpatients respectively , however these estimates are limited to patients with laboratory confirmed influenza. In addition, there are inherent differences in the performance characteristics of the currently used diagnostic tests . Lack of standardization between diagnostic tests and algorithms used in", "Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data\nPassage: It is interesting to note that on average, our simple rules yielded a PPV of 0.84 and an NPV of 0.75. This means that on average, rules will correctly predict an abnormal laboratory result 5 times out of 6 and correctly predict a normal result 3 times out of 4. While not good enough to replace testing , these observations raise the question of how much better prediction can get. Integration of information not considered in the present study, including vital signs, chief complaints, and physical findings, may improve prediction by these methods. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: in this study we did not set out explicitly to make a statement about repeat laboratory testing, the appropriateness of which has been investigated elsewhere , these results suggest that repeat laboratory testing within one week does not always add information that could not have been anticipated from the previous result. Refining this observation using the same unbiased approach we have followed here is potentially an area for future investigation. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: Laboratory testing is the single highest-volume medical activity . Its main role is to help adjust the level of clinical suspicion of a diagnosis to help rule it in or out; it is also used for disease monitoring. In practice, the level of clinical suspicion and the probability of a given test result can be correlated: the higher the suspicion, the more likely it is that the result will confirm the diagnosis. Information that feeds into the clinical suspicionincluding the age and gender of the patient, prior diagnoses, and prior laboratory results-thus may also influence the test result. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: We used four types of input-age, gender, diagnoses , and results of laboratory tests on blood samples added to the record in the seven days before a given test was ordered-to build simple, robust models for whether the result of a test would be within the reference interval or outside of it in a given direction , treating high and low results separately.", "Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: Real-time PCR is much more sensitive than other methods of detection and is available for detecting influenza virus but is more expensive. Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: Rapid laboratory diagnosis is critical for infection control, so several diagnostic tests have been developed and are available for the detection of influenza viruses. Rapid influenza diagnostic tests are less sensitive and specific than fluorescent antibody assays and RT-PCR . RT-PCR is the preferred diagnostic assay for influenza virus. These tests are the most sensitive and specific and can differentiate between influenza types and subtypes . The main problem of this technique is that it could not be available in all laboratories, so there is a need of other tests in these settings. Title: Application of Molecular Diagnostic Techniques for Viral Testing", "Passage: A rapid and sensitive detection of enterovirus in CSF could be performed by the introduction of real-time PCR techniques in the laboratory. Real-time PCR assays amplify conserved target nucleic acid sequences of the virus. Sensitivity for detecting enterovirus is similar between conventional PCR and real-time PCR but the last one is less labor intensive and easier to implement in the clinical laboratory . Title: Reliability of clinical diagnosis and laboratory testing techniques currently used for identification of canine parvovirus enteritis in clinical settings", "Passage: Various techniques of viral identification are used for the definitive confirmation of infection by CPV-2, for example, rapid tests based on immunochromatography are widely used by clinicians, because the procedure is easy, fast and accessible. Additionally, it doesn't require sample preparation or sending to a specialized laboratory for analysis. The varying sensitivity of this test is its downside; several studies have indicated that its sensitivity ranges from 50 to 100% , and in our study, the comparative sensitivity with nPCR was 66.6%. Some studies have suggested that the low technique sensitivity is due to the need of a large viral", "Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus\nPassage: Researches showed that the R 0 of severe acute respiratory syndrome was about 2.7-3.4 or 2-4 in Hong Kong, China . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 . The transmissibility of the Middle East respiratory syndrome is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 , with the inter-human transmissibility of the disease was about Title: Quantifying social distancing arising from pandemic influenza", "Passage: We suggest that, of these three estimates, the survey-based estimate of the clinical attack rate is probably closest to the true value of the serological attack rate and hence our preferred estimate of R 0 is 1.76 . Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Secondly, the R0, the basic reproduction number, is correctly described as the average number of infections each case causes. But it lacks two key ideas: 1) the 0 after the R implies the native state, which is a fully susceptible population and without any control measures. R is the effectiive number and can include the impact of control measures. Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: We obtained R 0 by first turning off all intervention policies prior to simulation. We then randomly infect one susceptible person and simulate the model, noting down the number of people he/she transmits the virus to. This process is repeated 1000 times, and the average number of transmissions is reported as the R 0 value. With the default parameters, we computed R 0 in the model to be approximately 1.9. To see the effectiveness of the various diagnostic approaches and intervention policies under different viral transmissibility, we vary R 0 from 1.6 to 2.3 by manually adjusting the transmission coefficients", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: SSA is an optimization technique introduced by . It simulates the Salps' behavior in nature. This behavior is called salp chain. The mathematical model of SSA begins by splinting its population into a leader group and followers group. The leader is the front salp, whereas, the followers are the other salps. The search space is determined in n-dimensions with n variables. Equation works to update the salps' positions. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: In the current study, we propose an improved ANFIS model based on a modified flower pollination algorithm using the salp swarm algorithm . The FPA is an optimization algorithm proposed by Yang , which was inspired by the flow pollination process of the flowering plants. The FPA was employed in various optimization applications, for example to estimate solar PV parameter , solving sudoku puzzles , feature selection , antenna design , and other applications . Moreover, SSA is also an optimization algorithm proposed by Mirjalili et al. inspired by the behavior of salp chains. In recent years, the SSA was Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: However, individual SI algorithms may stock at local optima. Therefore, one solution is to apply hybrid SI algorithms to avoid this problem. In , a hybrid of two SI algorithms, namely GA and SSA, was presented to improve the ANFIS model. The proposed new model called GA-SSA-ANFIS was applied to forecast crude oil prices for long-term time series data. However, the previously mentioned methods suffer from some limitations that can affect the performance of the forecasting output such as slow convergence and the ability to balance between exploration and exploitation phases can influence the quality of the final output. This Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: On the other hand, the updating phase of the followers' positions in the SSA algorithm is applied to improve the global pollination phase in the FPA algorithm. In this improvement, there is a random variable used to switch between both phases. If r > 0.5, then the operators of the SSA is used; otherwise, the operators of the FPA are used. In general, The FPASSA starts by constructing the population ; afterward, the objective function is calculated for each solution. The solution with the lowest error value is saved to the next iteration. This sequence is repeated until meeting the", "Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model\nPassage: risk. Cities are characterised by highly intense poultry trade activities involving live poultry markets, food markets, slaughterhouses, and poultry plants. This intensity may have resulted in increased possibilities of virus introduction and spread in surrounding areas. If the HPAI virus was transported through the road networks, the subdistricts located a short distance from the highway junction were more likely to be in contact with the virus than those situated further away. Highway junctions thus may have functioned as ''dissemination nodes'' for the HPAI H5N1 virus. A significant association was identified between a high HPAI risk and proximity to the closest Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: litter, and poultry manure were transported along collection circuits. The movement of live poultry, people, and infected material may have resulted in the spread of the virus between houses through direct or indirect transmission. Subdistricts with a high road density were associated with an increased risk of HPAI H5N1. Local poultry product and by-product business activities involve frequent contacts which revolve around road networks. Once the HPAI virus was introduced into a subdistrict, a dense road network may have facilitated its local spread. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model\u2019s predictability. Similarly, landscapes where Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: Subdistricts with a low average altitude were associated with a high risk of HPAI. The mixture of wetlands, ponds, irrigation networks and agriculture in these areas combined with intensive land use , may have constituted a favourable environment for the HPAI H5N1 virus. In contrast, subdistricts with a medium altitude have higher slopes and a land cover dominated by forests and permanent vegetation . Medium average altitude in subdistricts associated with low RR was found to constitute a kind of protective factor regarding HPAI risk. We also provide new insight into the role of factors related to poultry farming in", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: Another mechanism that viral infections may use to drive acute exacerbations is the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. Infection with a multitude of respiratory viruses causes disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells. For example, IFV infection was found to induce oncostatin M which causes tight junction opening . Similarly, RV and RSV infections usually cause tight junction opening which may also increase the infiltration rate of eosinophils and thus worsening Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In humans, overt disease was given the name Middle East respiratory syndrome, with the acronym MERS. From intermittent animal-to-human spill-over events, the MERS-CoV spreads sporadically among people, causing more severe disease among older adults, especially males, with pre-existing diseases. The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: mortality. It remains unclear if this group are uniquely affected by MERS-CoV or if other respiratory virus infections, including those from HCoVs, produce a similarly serious impact. In South Korea, a single imported case created an outbreak of 185 cases and 36 deaths that had a disproportionate impact on economic performance, community behaviour and trust in government and the health care system. Household human-to human transmission occurs but is also limited. Educational programs will be essential tools for combatting the spread of MERS-CoV both within urban and regional communities and for the health care setting.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: surface , and the term \"phage-displayed library\" to refer to a diverse pool of recombinant filamentous phage displaying an array of polypeptide variants . Such libraries are typically screened by iterative cycles of panning against an immobilized protein of interest followed by amplification of the bound phage in E. coli cells. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: surface , and the term \"phage-displayed library\" to refer to a diverse pool of recombinant filamentous phage displaying an array of polypeptide variants . Such libraries are typically screened by iterative cycles of panning against an immobilized protein of interest followed by amplification of the bound phage in E. coli cells. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date.", "Title: Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue\nPassage: In addition to the capsule, pneumolysin is a major virulence factor of S. pneumoniae . PLY is a member of the cholesterol-dependent cytolysins expressed by various Gram-positive bacteria. PLY of most pneumococci binds to cholesterol-containing membranes, forms pores upon oligomerization, and thereby causes cell lysis . At sublytic concentrations, PLY has been described to activate the complement system and to stimulate cytokine production in monocytes and macrophages . Moreover, PLY has been implicated in biofilm formation, independent of its haemolytic activity . Studies in mouse models of primary pneumococcal pneumonia demonstrated that PLY-deficient strains are more rapidly cleared from the Title: Prevalence, pathogenesis, therapy, and prevention of cardiovascular events in patients with community-acquired pneumonia", "Passage: Pneumolysin is increasingly implicated in the pathogenesis of life-threatening acute cardiac complications in CAP, albeit based on data derived from experimental animal models. Brown et al. have reported that experimental invasive pneumococcal disease in mice and rhesus macaques was associated with myocardial damage and formation of cardiac microlesions. Translocation of the pneumococcus into the myocardium appeared to be dependent on the pneumococcal adhesins, choline-binding protein A and phosphorylcholine, while microlesion formation was mediated by pneumolysin . Similar microlesions were detected in cardiac sections from patients with fatal IPD . The authors concluded \"that the microlesions and the scarring that occurs Title: Prevalence, pathogenesis, therapy, and prevention of cardiovascular events in patients with community-acquired pneumonia", "Passage: In addition to the aforementioned mechanisms, we have recently observed that the major protein virulence factor of the pneumococcus, pneumolysin, activates the production of platelet-activating factor by human neutrophils in vitro. These effects, which were observed at pathologically relevant concentrations of the toxin, were dependent on its cholesterol-binding, pore-forming activity and unrelated to interaction with TLR4 . In this context, it is noteworthy that PAF has been reported to contribute significantly to pneumolysin-induced lung injury in a murine model of experimental infection . We have also observed that pneumolysin, also at pathologically relevant concentrations, activates platelets directly, according to upregulated Title: Neutrophil gelatinase-associated lipocalin as a potential novel biomarker for ventilator-associated lung injury", "Passage: wild-type mice, which were divided into 7 groups. The protocol for the control group was spontaneous breathing for 2 h. The protocol for the high peak inflation pressure group was breathing under the condition of 50 cm H 2 O of PIP and 2. Table I .", "Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames\nPassage: two new possible initiation codons for these genes, located 3 of the annotated BKRF3 AUG. More work will be needed to learn whether they correspond to translation products from the distinct BKRF3, BKRT9 or the BKRT10 transcripts, or are instead all translated from the BKRF3 transcript. Title: Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China", "Passage: The employed recombination detection methods revealed that SAIBK is a chimera virus, with recombination by the SC021202 strain as a major parent and the H120 vaccine strain as a minor parent. The first and second recombination regions were located at positions 7231 to 9126 and 13437 to 14473 in genes 1a and 1b, respectively. There were two other recombination regions detected at positions 951 to 1067 and 5393 to 5605 of SAIBK, which were recombined with the SC021202 strain as a major parent and the H52 vaccine strain as a minor parent. The recombination detection results suggested that SAIBK is Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: We could map new alternative translation initiation sites located upstream or downstream of previously identified initiation codons, thereby extending or truncating the main protein product, up to 101 amino acids in the case of the BKRF3 protein . These alternative initiation codons were either AUGs or CUGs . The analysis of the BKRF3 gene was particularly interesting as it exemplifies the complexity of translation in the EBV genome . This gene overlaps with several newly identified lytic transcripts, including BKRT9 and BKRT10 that are contained within the BKRF3 locus, and is readily followed by the BKRF4 gene. We could identify Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: The libraries generated from infected cells treated with harringtonine revealed the existence of 25 short open reading frames with a size ranging from 1 to 74 amino acids . These ORFs were located upstream of wellcharacterized genes and thus represent upstream open reading frames . We investigated the parameters that have been found to influence the strength of the uORF, including their Kozak sequence, the cap to first uORF distance and the distance from last uORF to the main ORF . The sequences of the four shortest uORFs were perfectly conserved in all 115 EBV strains for which this sequence", "Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?\nPassage: A lot of the experimental studies on disease mechanisms and immune responses are based on a subsequent bacterial infection within hours or a few days post IAV infection. However, bacterial infiltrations of the lungs might occur much later, i.e., during the onset of wound healing after partial clearance of IAV, which has been reported in most studies performed in recent years . These processes are characterized by a general anti-inflammatory state and suppression of mechanisms involved in pathogen clearance due to increased interleukin-10 production . The anti-inflammatory state suppresses the expression of pattern recognition receptors on professional phagocytes leading to Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: A lot of the experimental studies on disease mechanisms and immune responses are based on a subsequent bacterial infection within hours or a few days post IAV infection. However, bacterial infiltrations of the lungs might occur much later, i.e., during the onset of wound healing after partial clearance of IAV, which has been reported in most studies performed in recent years . These processes are characterized by a general anti-inflammatory state and suppression of mechanisms involved in pathogen clearance due to increased interleukin-10 production . The anti-inflammatory state suppresses the expression of pattern recognition receptors on professional phagocytes leading to Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: pyogenes . The host inflammatory state in response to viral infection can alter presentation of receptors on the surface, thus allowing bacterial invasion . As the patient begins to recover from viral infection, secondary bacterial infections might occur due to the incomplete wound healing and exposure of host membrane components, including laminin, collagens type I and IV to classical bacterial MSCRAMMs . Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?\nPassage: pyogenes . The host inflammatory state in response to viral infection can alter presentation of receptors on the surface, thus allowing bacterial invasion . As the patient begins to recover from viral infection, secondary bacterial infections might occur due to the incomplete wound healing and exposure of host membrane components, including laminin, collagens type I and IV to classical bacterial MSCRAMMs .", "Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France\nPassage: In the two academic hospitals, Saint-Louis hospital in Paris and Tours hospital , influenza-like illness was defined as a patient suffering from at least one general symptom and one respiratory symptom , in agreement with the guidelines from the French Institut de Veille Sanitaire , a governmental institution responsible for surveillance and alert in all domains of public health . Criteria for severe clinical presentation were temperature below 35uC or above 39uC despite antipyretic, cardiac frequency above 120/min, respiratory frequency above 30/min, respiratory distress, systolic arterial pressure below 90 mmHg or altered consciousness. Predisposing factors of critical illness were children Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France", "Passage: Text: In order to monitor the spread of influenza and alert health handlers, several epidemiological tools have been developed. In France, a network of 1300 general practitioners, ''R\u00e9seau Sentinelles'', working throughout the country, provides real-time clinical data used to evaluate regional and national influenza spreading . The criteria used by this network to define clinical influenza-like illness are the occurrence of a sudden fever above 39uC with myalgia and respiratory signs. In general no formal viral diagnosis is carried out. The Groupes R\u00e9gionaux d'Observation de la Grippe is a second French network that surveys the emergence and the spread of Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France", "Passage: Clinical data were collected at the time of medical attention and reported by clinicians on a national standardized questionnaire provided by InVS . This questionnaire included the presence or absence of the main general and respiratory symptoms associated with ILI . Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: ILI was defined as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. Every week, all GPs of the sentinel network were encouraged to collect a nasal swab from the first two patients who presented ILI since less than three days. After being tested for influenza viruses, the 994 swabs collected in 2011 and 2012 are frozen at -80\u00b0C at the university hospital center laboratory.", "Title: Current and Novel Approaches in Influenza Management\nPassage: LAIV viruses in the nasopharynx elicit immune response that epitomizes a natural influenza infection. For this reason, LAIV has shown some superiority over the IIV in terms of the induction of mucosal immunity via secreted immunoglobulin A . Use of the LAIV has proven to be safe in children and immunocompromised persons . The most spelt-out advantage is the \"non-invasive\" capacity of the attenuated viruses and this had made it suitable to use for all categories of vaccines, although LAIVs are not recommended for people with underlying chronic medical conditions . A typical setback to the use of the LAIV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: in humans . Currently, NA-specific antibody responses are not considered a correlate of protection . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx . LAIV immunization induces serum antibody responses, mucosal antibody responses , and T cell responses. While robust serum antibody and nasal wash antibody responses are associated with protection from infection, other immune responses, such as Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: decade and it has been reported to protect young individuals better than IIV . Importantly, recent studies showed that LAIV can pre-sensitize the population and, subsequently, synergistically boost the efficacy of IIV . It should be noted that the use of LAIV in poultry requires strict safety standards due to concerns about the possibility that wild type strains may circulate in domestic poultry without apparent clinical symptoms, undergo genetic reassortment with the vaccine virus, and produce novel virulent strains . An ideal poultry LAIV should not be able to revert to wild type virus or undergo reassortment with field strains. Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens\nPassage: be a big advantage in young birds which have limited numbers of functional antigen presenting cells . In addition to the general advantages of live vaccine, our LAIV is highly immunogenic via the action of truncated NS1 protein as proved in our previous studies .", "Title: CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy\nPassage: subordinate genera Salinibacter and Rhodothermus belongs to an uncertain order of the phylum Bacteroidetes. But in CVTree, it is the nearest neighbor to the phylum Chlorobi. Corresponding lineage modification leads to monophyletic Bacteroidetes{88 + 5} and Chlorobi {13 + 5}. Title: Bayesian Phylogeography Finds Its Roots", "Passage: We further annotated the tree nodes with their most probable In combination with other topological differences between the trees, this difference strongly suggests past reassortment events between both segments, with the progenitor virus of the basal Hong Kong clade and a chicken strain from Hebei having acquired an NA segment from different lineages. Such events are not surprising given frequent reports of A-H5N1 reassortment in China, e.g. , and the particular reassortment event for the basal Hong Kong clade has very recently been confirmed . Title: Improved phylogenomic sampling of free-living nematodes enhances resolution of higher-level nematode phylogeny", "Passage: limited. Interestingly, the PhyloTreePruner-based analysis recovers the traditionally hypothesized placement of Onychophora as the sister taxon of Arthropoda with strong support but in the SCaFoS-based analysis, it is recovered as the sister taxon of a clade of all other nonscalidophoran ecdysozoans with maximal support. The limited taxon sampling for key ecdysozoan clades further demonstrates the need for high-quality genomic and transcriptomic resources from this part of the animal tree. Title: CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy", "Passage: The clearest distinction of the CVTree phylogeny and 16S rRNA analyses arises from the phylum Spirochaetes. Species in this phylum were placed together mainly based on their morphological similarities in the first edition of the Manual. Carl Woese described that spirochaetes form a single clade according to 16S rRNA features . Taxonomically, the phylum Spirochaetes consists of a single class, which in turn is composed of one order. Therefore, only the rank family makes sense. In CVTree, the three monophyletic families Spirochaeta-ceae{44}, Brachyspiraceae{7}, and Leptospiraceae{8} do not join each other, but the first two are closer together.", "Title: Detection of a Fourth Orbivirus Non-Structural Protein\nPassage: Bioinformatic analyses indicate that NS4 contains coiled-coils and is structurally related to other mammalian proteins, with helical or coiled-coil regions. These analyses also suggest that the NS4 may be functionally related to proteins involved in nucleic acid binding, or associated with lipids and membranes. Nuclear localisation signals were predicted in NS4 of PHSV, YUOV, EHDV, BTV, AHSV and GIV. All these proteins are rich in arginine and lysine residues that are essential for NLS . Title: Detection of a Fourth Orbivirus Non-Structural Protein", "Passage: The icosahedral orbivirus core-particle is constructed as two concentric protein shells, the sub-core layer which contain 120 copies/particle of the T2 protein , and the coresurface layer composed of 780 copies/particle of the T13 protein . VP1, VP4 and VP6 are minor enzymatic proteins that are packaged along with the ten genome segments within the central space of the virus core . The orbivirus outer-capsid layer is composed of two additional structural proteins , which mediate cell-attachment and penetration during initiation of infection. These outer-capsid proteins are more variable than the core proteins and most of the non-structural proteins, and Title: Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins\nPassage: the structural proteins. Title: Detection of a Fourth Orbivirus Non-Structural Protein", "Passage: the structural proteins. Title: Detection of a Fourth Orbivirus Non-Structural Protein\nPassage: We report the synthesis and detection of NS4, in the cytoplasm and nuclei of cells infected with insect-borne and tick-borne orbiviruses .", "Title: The role of viral persistence in flavivirus biology\nPassage: the infection followed by a down-regulation that favors the expression of TGF-b . A continued up-regulation of the cytokines could be detrimental to the cell, and the virus would fail to persist. Results of a recently established animal model also show that host-adapted SNV achieves prolonged and disseminated infection, with no disease in hamsters . Therefore, hantaviruses may have evolved mechanisms of manipulating target genes, which establishes persistence when induced. Title: The role of viral persistence in flavivirus biology\nPassage: additional research. Title: The role of viral persistence in flavivirus biology", "Passage: additional research. Title: The role of viral persistence in flavivirus biology\nPassage: yellow fever virus , West Nile virus , Japanese encephalitis virus , and dengue virus serotypes 1-4. Infections with all of these viruses can lead to severe disease, prolonged debilitating neurological sequelae, hemorrhagic fever, and/ or death in some cases . Viral persistence is a hallmark of the ecology of VBFVs. Both TBFVs and MBFVs are cycled between arthropod and vertebrate hosts , and in many cases, they are maintained without deleterious effects on the hosts. In nature, TBFVs, such as POWV and TBEV, alternately infect small vertebrates such as rodents, hares, some carnivores, and a range of hard-bodied ticks, Title: The role of viral persistence in flavivirus biology\nPassage: induces an acutely cytopathic infection in mammalian cells, and thus, the development of a persistent infection implies that cell death factors must be evaded or modulated, although the precise mechanisms are still obscure.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: . The massive cell death induced may result in worsening of the acute exacerbation due to the release of their cellular content into the airway, further evoking an inflammatory response in the airway . Moreover, the destruction of the epithelial barrier may cause further contact with other pathogens and allergens in the airway which may then prolong exacerbations or results in new exacerbations. Epithelial destruction may also promote further epithelial remodeling during its regeneration as viral infection induces the expression of remodeling genes such as MMPs and growth factors . Infections that cause massive destruction of the epithelium, such as Title: Epithelial Cell Apoptosis and Neutrophil Recruitment in Acute Lung Injury\u2014A Unifying Hypothesis? What We Have Learned from Small Interfering RNAs", "Passage: destruction of its integrity prompts a progressive influx of proteinrich fluid into the alveoli . On the other hand, the loss of epithelial integrity represents an impairment of the physiologic trans-epithelial fluid transport and further inhibits the re-absorption of the alveolar edema . Thus, while an isolated injury to the endothelium still leaves intact the capacity of the epithelium to counteract pulmonary edema formation, the fluid balance becomes rapidly disturbed upon injury of the lung epithelium . Therefore, it is not surprising that the extent of epithelial damage and impaired edema re-absorption was linked clinically to outcome in ALI . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: On the other end of the spectrum, viruses that induce strong type 1 inflammation and cell death such as IFV and certain CoV , may not cause prolonged inflammation due to strong induction of antiviral clearance. These infections, however, cause massive damage and cell death to the epithelial barrier, so much so that areas of the epithelium may be completely absent post infection . Factors such as RANTES and CXCL10, which recruit immune cells to induce apoptosis, are strongly induced from IFV infected epithelium . Additionally, necroptotic factors such as RIP3 further compounds the cell deaths in IFV infected epithelium Title: Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions", "Passage: The damage of the epithelial cells promotes streptococcal infection in different ways. It results in the loss of their barrier function and allows the bacteria to get access to deeper areas of the epithelium that are usually not exposed to the environment. This conclusion is supported by our infection studies with PCLS, another culture system for differentiated airway epithelial cells 37 . It has been suggested that dead cells may provide a rich source of nutrition and growth factors and thus enhance streptococcal growth 48 . We found larger numbers of bacteria in areas where the epithelium had been damaged.", "Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers\nPassage: Abstract: The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World and New World complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: Text: The virus family Arenaviridae consists of only one genus, but most viruses within this genus can be divided into two different groups: the Old World arenaviruses and the New World arenaviruses . The differences between the two groups have been established through the use of serological assays. Most of the arenaviruses cause persistent infection in rodents without any symptoms, and humans acquire a variety of diseases when zoonotically infected. Lymphocytic choriomeningitis virus is the only arenavirus to exhibit a worldwide distribution, and causes illnesses such as meningitis . Congenital LCMV infections have also been reported . Most importantly, viral Title: Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors", "Passage: The family Arenaviridae is divided into 3 genera based on their natural hosts-Mammarenaviridae, Reptarenaviridae, and Hartmaniviridae that include viruses infecting mammals, reptiles, and fish, respectively . Mammarenaviridae are further classified into the regions of their origins, such as the Old World viruses found in West Africa and the New World viruses found in South America , which are believed to have originated <23,000 and 41,000 years ago in those continents, respectively . Additionally, several NW arenaviral strains have been discovered in the United States, which are suspected to potentially cause human FIGURE 1 | Taxonomy and location of arenaviruses. The Title: Use of Recombinant Adenovirus Vectored Consensus IFN-\u03b1 to Avert Severe Arenavirus Infection", "Passage: The Arenaviridae family of viruses has several members that can cause viral hemorrhagic fever, an acute, often-fatal, viral syndrome characterized by intense fever, malaise, and less frequently, bleeding and neurologic manifestations. Case fatality rates of hospitalized patients suffering from arenaviral hemorrhagic fever range from 15-30% . Arenaviruses known to cause AHF include Jun\u00edn, Machupo, Guanarito, Sabi\u00e1, and Chapare in the South American continent, and Lassa and Lujo in west and southern Africa, respectively. Primary transmission of the arenaviruses from respective rodent reservoir hosts to humans occurs via exposure to contaminated excreta . Person-to-person transmission can occur through contact with blood", "Title: Host resilience to emerging coronaviruses\nPassage: Both viral infections elicit a very strong inflammatory response, and are also able to circumvent the immune response. There appears to be several ways that these viruses evade and otherwise redirect the immune response . The pathways that lead to the induction of the antiviral type I interferon response are common targets of many viruses, and coronaviruses are no exception. SARS-CoV and MERS-CoV are contained in double membrane vesicles , that prevents sensing of its genome . As with most coronaviruses several viral proteins suppress the type I IFN response, and other aspects of innate antiviral immunity . These alterations Title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity\nPassage: unclear how the host immune response overcomes viral evasion to initiate a protective antiviral response. Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: Detection by the PRRs would activate signaling cascades leading to the production of type I IFNs, resulting in the establishment of an antiviral state. Thus, coronaviruses do not just avoid detection by the host immune system, which appears to be the main strategy of ensuring successful replication ; some viruses also encode proteins that function to disrupt the downstream signaling cascades at various points, preventing the establishment of an effective antiviral state when detection of the viral PAMPs has occurred. Indeed, the N protein has also been shown to interfere with the 2', 5'-oligoadenylate synthetase/RNaseL activation that occurs downstream of Title: Haunted with and hunting for viruses\nPassage: discovery of new pathogens. Soon the receptor used by MERS-CoV to enter the host cells was identified and the molecular basis of the receptor binding to the virus was also elucidated recently .", "Title: Viral vector-based influenza vaccines\nPassage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adenovirus vectors are attractive as vaccine vectors because their genome is very stable and there are a variety of recombinant systems available which can accommodate up to 10 kb of recombinant genetic material . Adenovirus is a non-enveloped virus which is relatively stable and can be formulated for long-term storage at 4 \u00b0C, or even storage up to six months at room temperature . Adenovirus vaccines can be grown to high titers, exceeding 10 1\u00b0 plaque forming units per mL when cultured on 293 or PER.C6 cells , and the virus can be purified by simple methods . Adenovirus vaccines Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: Delivery of recombinant adenoviral vaccines to either the nasal or intestinal mucosa is an attractive vaccination strategy for many reasons. Vaccines administered in this manner will offer improved safety with respect to disease transmission and needle-stick injuries among health care workers, significant issues of concern in developing countries where the demand for many vaccines is high . Mucosal administration of vaccines reduces the pain associated with vaccination, eliminates the need for specialized training programs for large vaccination campaigns and makes selfadministration of the vaccine possible. This route of administration may also significantly reduce systemic toxicity associated with recombinant adenovirus despite Title: Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine", "Passage: Viral vectored vaccines are known to be an effective mechanism to induce cellular responses compared with subunit vaccines and can induce protective T cell responses against intracellular pathogens . Recombinant viruses are excellent vehicles for vaccine delivery as viral proteins can act as potent adjuvants and can directly infect antigen-presenting cells . Adenoviruses are highly attractive vectors for human vaccination as they possess a stable genome which prevents inserts of foreign genes from being deleted and they can infect large numbers of cells without any evidence of insertional mutagenesis .", "Title: CDC Summary 21 MAR 2020,\nPassage: All 50 states have reported cases of COVID-19 to CDC. Title: CDC Summary 21 MAR 2020,\nPassage: Twenty-seven U.S. states are reporting some community spread of COVID-19. Title: CDC Summary 21 MAR 2020,\nPassage: More cases of COVID-19 are likely to be identified in the United States in the coming days, including more instances of community spread. CDC expects that widespread transmission of COVID-19 in the United States will occur. In the coming months, most of the U.S. population will be exposed to this virus. Title: CDC Summary 21 MAR 2020,\nPassage: As of the evening of March 17, 89 state and local public health labs in 50 states, the District of Columbia, Guam, and Puerto Rico have successfully verified and are currently using CDC COVID-19 diagnostic tests.", "Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: anorexia, nausea, and vomiting. Additional potential symptoms include headache, muscle and joint aches, sore throat, confusion, fatigue, shortness of breath, chest pain, and occasionally a maculopapular rash. Hiccups are an established symptom; while not universal, they may help to distinguish EVD and Marburg infection from those disorders with similar presentations such as malaria and Dengue. Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Symptoms are common to each infection and manifest on a gradient. Generally, but far from always, influenza infection is more likely to result in a patient feeling so unwell as to take to their bed and have a fever, than RSV, an HRV, CoV or other common cold virus infection, during which daily life is usually less impacted. Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study\nPassage: Among the fatal cases, cough was the most commonly reported symptom . Other symptoms reported were fever , shortness of breath , muscle pain , headache , vomiting , runny nose , diarrhoea , sneezing and sore throat . Title: The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS)", "Passage: The most commonly reported symptoms among episodes of disease were respiratory , including coughing, sneezing/runny nose, sore throat and dyspnoea, in decreasing order. Other disease episodes included: fever , headache , body aches , and digestive disorders , including diarrhoea and vomiting/nausea.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Despite the many advantages which viral vectoring can offer, pre-existing immunity is a major obstacle of many viralvectored vaccines, such as Ad serotype 5 or herpes simplex virus type 1 , where the rate of seroprevalence to these viruses is very high of the US population, respectively] . Vector-specific antibodies may impede the induction of immune responses to the vaccine-encoded antigens, as they may reduce the dose and time of exposure of the target cells to the vaccinated antigens . In a large-scale clinical trial of an Ad serotype 5 -based HIV-1 vaccine, the vaccines showed a lack of efficacy Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Similarly studies of L. monocytogenes and the effects of preexisting immune responses indicate conflicting results. A study by Bouwer et al. indicates that pre-existing immune responses against the Listeria vector do not diminish immune responses against the delivered heterologous antigen, and a similar study by Starks et al. also concluded that prior exposure of mice to the empty Listeria vector did not influence anti-cancer immune responses when a similar mutant was used as a carrier of a melanoma cancer antigen. Similar findings were reported by Whitney et al. in rhesus macaques in which L. monocytyogens was used as a carrier Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Conversely, there are reports that indicate that pre-existing immunity against the bacterial vector downregulates immune responses against the delivered heterologous antigen using similar or related vectors. Attridge and coworkers reported that the presence of immunity against the bacterial vector prior to the delivery of vectored antigenic", "Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research\nPassage: One review author assessed the titles and abstracts of the identified records and removed all records that were clearly not relevant. Both review authors then independently assessed the eligibility of the remaining records. The full text of all the papers identified as potentially relevant by one or both review authors were retrieved. These papers were then assessed independently by both review authors. Disagreement between review authors was resolved through discussion. Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research", "Passage: Both review authors independently applied a set of quality criteria to each included study. Any disagreements between the two review authors were then resolved through discussion. The review authors appraised the studies using the main elements of the Critical Appraisal Skills Programme quality assessment tool for qualitative studies , as in other syntheses of qualitative evidence . We did not exclude studies because of low study quality. Title: What\u2019s Past is Prologue: A Scoping Review of Recent Public Health and Global Health Informatics Literature", "Passage: Multiple volunteers from the PHI and GHI working groups assisted with review of candidate articles. Two authors divided the candidate articles into relatively equal numbers and assigned them to reviewers. Reviewers examined titles, abstracts, and other article metadata, recommending inclusion or exclusion based on the defined criteria. Each article was reviewed by at least two individuals, and disagreements were resolved after further review by the team leads . Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: While well-done reviews in a large number of areas are available, it is important to continue to improve the quality of the overall body of public health review literature. Considering that the majority of weak reviews scored poorly on assessing the methodological quality of the primary studies, transparency, methods for combining or comparing results, conducting a comprehensive search strategy, and data supporting the author's interpretations, review authors should be cognisant of these criteria when conducting systematic reviews. In improving the quality of systematic reviews, the overall goals should ensure there are high quality reviews in all public health topic areas", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Ninety-five percent of infected adults are symptomatic after infection, and of these, most become disabled for weeks to months as a result of decreased dexterity, loss of mobility, and delayed reaction. Eighteen months after disease onset, 40% of patients are found to still have anti-CHIKV IgM . The chronic stage of CHIKF is characterized by polyarthralgia that can last from weeks to years beyond the acute stage . CHIKV has been shown to attack fibroblasts, explaining the involvement of muscles, joints, and skin connective tissues. The high number of nociceptive nerve endings found within the joints and muscle connective tissues Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: More than 50% of patients who suffer from severe CHIKF are over 65 y old, and more than 33% of them die. Most adults who suffer from severe CHIKF have underlying medical conditions . The other group that is disproportionately affected by severe CHIKV is children. Other complications associated with CHIKV, from most common to least common, include respiratory failure, cardiovascular decompensation, meningoencephalitis, severe acute hepatitis, severe cutaneous effects, other central nervous system problems, and kidney failure . Title: Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity", "Passage: non-CHIKV-specific polyvalent IgG also died from infection . Nevertheless, viral RNA load in serum, liver and muscles was determined in CHIKV-infected mice receiving 10 \u00b5g/kg of CHIKVIGs. It was observed that enhanced CHIKV infection led to a more significant viral burden in the muscles at 3 dpi , but not at 6 dpi . Taken together, these findings highlight that enhanced CHIKV infection is detrimental in young animals. Title: Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity", "Passage: be seen if infants born to mothers infected with CHIKV during their pregnancy may suffer from a more severe disease due to the low levels of maternal-acquired CHIKV-specific antibodies. It was reported that newborn mice infected with DENV in the presence of maternally acquired anti-DENV antibodies had a more severe disease outcome 64 . Three-weeks old, C57BL/6 WT female mice were infected via footpad inoculation with 10 6 PFU of CHIKV. Immediately, these mice were administered intraperitoneally with ~2 \u00b5g/ml mice sera from CHIKV-infected mice or PBS . Daily assessment of viremia and disease score were performed. All Data are", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection", "Title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA\nPassage: consensus sequence of the cDNA used for the cloning procedure . These differences are non-representative variants within the cDNA. Overall, the BAC sequence differed from the cDNA sequence in 18 positions, 9 of these lead to predicted amino acid substitutions within the polyprotein; one in each of N pro , E rns , E1, E2 and NS3 and four amino acid substitutions in NS5B . When compared to the published reference sequence , the pBeloR26 BAC sequence differed at an additional 11 positions, 1 of these lead to a predicted amino acid substitution and there was one large insertion in Title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo", "Passage: of introducing undesired mutations by cell culture adaptation; The manipulation of BAC cDNA clones is relatively easy and similar to that of conventional plasmids with slight modifications due to the presence of only one plasmid copy per cell. In addition to standard protocols, the BAC cDNA clones could also be efficiently modified into E. coli by homologous recombination using a two-step approach that combine the Red recombination system and counterselection with the homing endonuclease I-SceI ; and The BAC approach has been successfully used to engineer infectious clones of other flaviviruses, including DENV , and several coronaviruses that contain the Title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo", "Passage: The BAC plasmid pBeloBAC11 , kindly provided by H. Shizuya , was used to assemble the ZIKV-RGN infectious cDNA clone. This plasmid is a synthetic low-copy-number plasmid based on the Escherichia coli F-factor that minimize the toxicity problems in the bacteria of exogenous sequences. E. coli DH10B cells were used to amplify the BAC plasmids. Electrocompetent DH10B cells were transformed by electroporation using a MicroPulser unit , according to the manufacturer's instructions. BAC-based plasmids were isolated and purified using the Large-Construct kit , following the manufacturer's specifications. Title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo\nPassage: and sequencing. No differences were detected, demonstrating that the ZIKV-RGN BAC clone was fully stable in bacteria and that the BAC approach is a reliable and simple method to generate ZIKV infectious cDNA clones.", "Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response\nPassage: The two leading causes of burden of disease in the world are infectious diseases -lower respiratory infections and diarrhoeal diseases. HIV/AIDS is now the fifth cause of burden of disease globally, and three other infectious diseases also appear in the top 15 causes . Title: Exposure science in an age of rapidly changing climate: challenges and opportunities", "Passage: Climate change and exposure to infectious disease agents. A large number of infectious disease agents cause morbidity and mortality both in the US and abroad, including foodborne, water borne, vector borne, zoonotic, and soil-associated agents. In the US, the burden of illness caused by infectious diseases each year is substantial. Foodborne diseases alone, many of which have strong links to the environment, are estimated to cause 9.4 million episodes of illness, resulting in 55,961 hospitalizations and 1351 deaths. 41 Waterborne diseases are also important, with between 4.26 and 11.69 million annual cases of acute gastrointestinal illness attributed to public drinking Title: Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction", "Passage: The most frequent infectious diseases in humans-and those with the highest potential for rapid pandemic spread-are usually transmitted via droplets during close proximity interactions . Such infectious diseases include influenza, common colds, whooping cough, SARS-CoV, and many others. Influenza alone leads to a projected annual cost of 2.0-5.8 billion USD for the American health-care system . It is critical to identify the group of individuals who are in close contact with the diagnosed patient, in order to understand and mitigate the spread of the aforementioned pandemic diseases. Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: The leading 10 causes of the burden of disease in 2004 included 4 communicable diseases. HIV/AIDS was the fifth leading cause of the burden of disease globally in 2004 and the leading cause in the WHO African Region, where it was followed by lower respiratory infections, diarrhoeal diseases and malaria. The WHO regions of South-East Asia, the Eastern Mediterranean and Africa are affected by a dual burden of disease . These WHO regions are much more heavily burdened by infectious disease and conditions related to pregnancy and childbirth than other regions, but they also suffer severely from the problems that", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: hospitalization, and ultimately die. 22 Early predictions for incubation time are between 2 and 14 days, based on data from similar coronaviruses. The 14-day criterion for epidemiological risk assumes the longest estimated incubation time. 23 In addition, the World Health Organization has created its own interim case definition. 24 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: One of the critical issues in infectious disease epidemiology is that the time of infection event is seldom directly observable. For this reason, the time of infection needs to be statistically estimated, employing a backcalculation method . Using a sophisticated statistical model with doubly intervalcensored likelihood and right truncation with an exponential growth of cases, the mean incubation period has been estimated to be about 5.0 days . To understand the time-dependent risk of infection throughout the course of outbreak and estimate the effectiveness of the quarantine measure from 5 to 19 February 2020, I aimed to estimate the incidence Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: because cases currently being detected and reported would have mostly been infected in mid- to late-January. Average delays between infection and illness onset have been estimated at around 5\u20136 days, with an upper limit of around 11-14 days , and delays from illness onset to laboratory confirmation added a further 10 days on average . Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: cases currently being detected and reported would have mostly been infected in mid-to late-January. Average delays between infection and illness onset have been estimated at around 5-6 days, with an upper limit of around 11-14 days , and delays from illness onset to laboratory confirmation added a further 10 days on average .", "Title: Antibody Engineering for Pursuing a Healthier Future\nPassage: Human diseases have been known for ages. The comfort of global travel and better interdependence have supplemented layers of intricacy to comprehend infectious diseases. These life threatening contagions effect human health in relation to unpredicted illnesses, deaths, and interfere many other normal life activities. Moreover, the diseases take a significant human toll as well as cause public fear . To date, limited knowledge is available on extended aspects of the production of antibodies by hybridoma technology, antibody engineering techniques, construction of antibody fragments, display technologies, and their extended applications . Therefore, to cope these health threats and limitations, extraordinary advances Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Conversely, engineered antibodies have various disadvantages such as they exhibit greater expense and complexity in manufacturing compared to antibodies developed by hybridoma technology . Due to their foreign nature, engineered therapeutic antibodies lead to allotypic immune responses that results in rapid clearance from body by kidney, elicit on T-cell help, and have reduced antibody avidity. Moreover, engineered antibodies exhibit reduced half-life due to lack of an Fc domain and prevention of FcRn-mediated recycling. Likewise, antibody based therapies have more limitations based on the fact that many targets have not yet been determined for various diseases . Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Therapeutic antibodies developed for the treatment of other infectious diseases include prophylaxis, anthrax, autoantibodypositive, lupus, angioedema, immune thrombocytopenic purpura, macular degeneration, hemophilia A, psoriasis, alzheimer, muscle loss and weakness, optic neuritis, ulcerative colitis, pulmonary fibrosis, and asthma . Title: Antibody Engineering for Pursuing a Healthier Future\nPassage: Similarly, engineered antibodies have been used for the treatment of various types of arthritis. Arthritis is a chronic multifactorial disease in which immune system attacks and starts degrading the body's joints . Therapeutic antibodies such as adalimumab, mavrilimumab, and GSK3196165 have been developed for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis .", "Title: Steps to a Sustainable Public Health Surveillance Enterprise A Commentary from the International Society for Disease Surveillance\nPassage: Technology that enhances communication and data sharing across disease programs, surveillance systems, and even across jurisdictions increases the ease of obtaining and disseminating useful information to a broad audience, including public health agencies, healthcare providers, policymakers, and the general public. 6, 32 This rapid information exchange not only facilitates timely response, but can also reduce emergency room visits, hospital admissions, and even costs of care. 33 However, many health departments currently have systems that are not flexible enough to respond to changing health IT needs, which makes it difficult to deliver information when and where it is needed. 4 Disease Title: Steps to a Sustainable Public Health Surveillance Enterprise A Commentary from the International Society for Disease Surveillance", "Passage: encouraging collaboration within and between departments, surveillance professionals can take advantage of shared platforms and resources to optimize data collection, analysis, storage, and dissemination, thus helping to reduce operational costs and improve efficiency. For example, collaboration could create opportunities for the effective integration of syndromic and reportable disease data for public health use. 36 Title: Steps to a Sustainable Public Health Surveillance Enterprise A Commentary from the International Society for Disease Surveillance\nPassage: threats to population health. By providing political commitment and financial support to this issue, decision makers can play an active role in advancing the health of individuals, communities, and nations. Title: Steps to a Sustainable Public Health Surveillance Enterprise A Commentary from the International Society for Disease Surveillance", "Passage: 1. Recognize systematic and ongoing public health surveillance as a core public health function that is essential for population health, economic stability, and national security. 2. Create and support funding mechanisms that reinforce enterprise , rather than categorical surveillance infrastructures and activities in order to reduce inefficient silos, leverage resources, and foster synergies. 3. Oppose further cuts to spending for surveillance activities. 4. Invest in surveillance workforce development to build competencies and improve organizational capacity to utilize technological advances in surveillance practice. 5. Advance a rigorous surveillance research and evaluation agenda that will deepen the understanding of community health, identify", "Title: Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer\nPassage: shrinkage could prevent genetic instability associated with repetitive sequences. On the other hand, Hmo1, a High Mobility Group protein involved in the specialized chromatin state at the rDNA , is regulated by TORC1 ; and Hmo1 was required alongside with condensin to mediate both a starvation-induced transcriptional position effect within the rDNA and nucleolar contraction . Mitotic rDNA condensation is also regulated by the Jhd2 demethylase, which acts on histone H3, the maintenance of Csm1/Lrs4 and condensin association with the rDNA . How is condensin activated outside anaphase under stress conditions? It was shown that the condensation of this locus Title: Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer", "Passage: technique and through the novel CRISPR/dCas9-GFP imaging technology . The rDNA loop has been extensively studied as a model for the chromosome condensation process that occurs in metazoan prophase, despite the controversy about whether yeast chromosomes actually condense as their higher eukaryotes counterparts. Regardless, the amenability of yeast genetics was determinant to test how the structural maintenance of chromosome complexes shape mitotic chromosomes . In these works, it was firmly established that both condensin and cohesin SMC complexes were essential for the transition from puff to loop. Another common partner with SMC complexes and key player in the condensation of Title: Functional ultrastructure of the plant nucleolus", "Passage: still ready to be woken up when needed . It seems probable that when nucleolar transcriptional activity increases, the incompetent chromatin turns into transcriptionally active r-genes which are disentangled and released from the FC-condensed chromatin , thus the number of active 45S rRNA genes may change according to the physiological needs of the cell . It means that the content of nucleolar-condensed chromatin can change according to the transcriptional activity of nucleoli. Indeed, such a correlation was observed in the nucleoli of soybean plants subjected to chilling, when nucleolar transcriptional activity was low, the increase in the content of condensed Title: Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer", "Passage: contraction and short-range chromatin compaction were shown to rely partially on the deacetylase Hst2 in order to promote chromosome condensation in anaphase by removal of acetyl groups from histone H4 . Thus, it is indeed feasible that sirtuins may directly control rDNA condensation. Post-translational modifications of histones are considered to promote chromatin compaction . Remarkably, H4K16 deacetylation is important for chromatin compaction by promoting H2A and H4 interaction , and this epigenetic mark at subtelomeric regions also regulates yeast lifespan . In addition, modifications mediated by acetyl transferases like Nat4, and the loss of histone H4 acetylation, were linked to", "Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase\nPassage: To test the application of the new RT-qPCR in quantification of gene expression, we established RT-qPCR assays based on the new method and the conventional method to quantify the expression of \u03b2-actin. The RNA standards were prepared from 1\u00d710 3 to 1\u00d710 7 copies/\u00b5l. Compared with the conventional method , the new method produced amplification curves with relatively lower Ct values and obviously stronger fluorescent signals, suggesting a higher sensitivity of the new method . The standard curves generated by both methods showed wide dynamic range scope from 1\u00d710 3 to 1\u00d710 7 copies/\u03bcl and consistent linear correlation coefficient . Title: Strand-Specific Quantitative Reverse Transcription-Polymerase Chain Reaction Assay for Measurement of Arenavirus Genomic and Antigenomic RNAs", "Passage: species via standard or QRT-PCR. Several approaches have been utilized for the purpose of detecting and/or quantitating the different viral RNA species generated during LCMV infection. These approaches have ranged from standard RT-PCR to screen for the presence or absence of a particular viral RNA species to Northern blot , in situ hybridization , or RNase protection assay to more accurately determine the quantities of a given target RNA. Limitations of the latter three assays include the requirement for large quantities of RNA and/or radioactive reagents coupled with limited sensitivity and throughput. The QRT-PCR assay we describe overcomes these limitations Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase", "Passage: All 7 samples were detected as positive by the new method, while only 4 were detected as positive by the conventional method , possibly due to low viral load. This result suggested that the HFman probe-based RT-qPCR has higher sensitivity than the TaqMan probe-based conventional RT-qPCR. Title: Strand-Specific Quantitative Reverse Transcription-Polymerase Chain Reaction Assay for Measurement of Arenavirus Genomic and Antigenomic RNAs\nPassage: and therefore is a valuable research tool for the field. Indeed, several groups from both basic and clinical research settings have reported the use of QRT-PCR approaches to quantitate LCMV RNA load . However, these assays were not designed to specifically track individual LCMV replicative RNA species. Additionally, for the assay that theoretically does prime for a specific viral RNA , nonspecific cDNA synthesis during RT was not taken into account.", "Title: Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization\nPassage: All viruses in the genus Flavivirus possess a single-stranded, positive-sense RNA genome of approximately 11 kb . The genome usually encodes a single open reading frame that is flanked by 5' and 3' untranslated regions of ~100 and ~400-700 nt, respectively . The ORF encodes a large polyprotein that is co-and post-translationally cleaved to generate three structural proteins, designated the capsid , premembrane/membrane and envelope proteins, and seven nonstructural proteins in the gene order: 5'-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-2K-NS4B-NS5-3' . The genomes of some flaviviruses appear to encode an additional protein as a consequence of ribosomal frameshifting as discussed later in this review. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: Flaviviruses have an approximately 11-kb positive-stranded RNA genome containing a single open reading frame flanked by untranslated regions at both termini. The ORF encodes three structural proteins, including the capsid , membrane and membrane ), and envelope , and seven nonstructural proteins . These seven nonstructural proteins participate in viral replication, virion assembly, and virus escape from immune surveillance. Title: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection", "Passage: Flaviviruses have an approximately 11-kb positive-stranded RNA genome containing a single open reading frame flanked by untranslated regions at both termini. The ORF encodes three structural proteins, including the capsid , membrane and membrane ), and envelope , and seven nonstructural proteins . These seven nonstructural proteins participate in viral replication, virion assembly, and virus escape from immune surveillance. Title: Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts\nPassage: We identified an incomplete flavivirus-related sequence in sample 7 . Flaviviruses have non-segmented single-stranded positive-sense RNA genomes of around 11 kb. The flavivirus genome contains a long ORF that is translated as a polyprotein. Structural proteins are encoded at the 5' end of the genome and non-structural proteins are encoded at the 3' end.", "Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China\nPassage: Text: The main challenge may include early identification of outbreak, rapid expansion of patients, high risk of nosocomial transmission, unpredictability of size impacted, and lack of backup resource. These challenges have caused severe shortage of healthcare workers, medical materials, and beds with isolation. The Spring Festival holiday has greatly aggravated the shortage of human resources and heavy traffic flow due to the vacation of healthy workers and factory workers, which further magnified the risk of transmission. The key point is to discriminate the infectious disease outbreak from regular clustering cases of flu-like diseases at early stage. There is a trade-off Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: hospitals be needed, and social media be employed. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management", "Passage: against a highly infectious disease while maintaining function at a high volume capacity. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: hospital\u2019s management and planning of infection control and radiology departments;", "Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland\nPassage: The length of the region from the p4.7 to p12.7 genes in the two viruses was 544 base pairs. Compared with NC99, Irish ECoVs, had a total of 37 nucleotide deletions within p4.7 and the non-coding region following the p4.7 gene. Compared with Obihiro 12-1 and 12-2, Irish ECoVs had a three-nucleotide insertion. When compared with Tokachi09, the Irish ECoVs had a 148-nucleotide insertion . The p12.7 gene of the two Irish ECoVs did not have deletions or insertions, and the nucleotide identities were 98.8-99.7% between these viruses and the other ECoVs . Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The complete genome sequence of 2019-nCoV HKU-SZ-005b was available at GenBank . The representative complete genomes of other related \u03b2CoVs strains collected from human or mammals were included for comparative analysis. These included strains collected from human, bats, and Himalayan palm civet between 2003 and 2018, with one 229E coronavirus strain as the outgroup. Title: Genetic diversity of the 2013\u201314 human isolates of influenza H7N9 in China", "Passage: A number of substitutions were detectable only in part of the short-read sequences and coexisted with the reference version; this is an indication of the presence of viral quasi-species carrying different versions of the protein . None of the Figure 2 Phylogenetic analysis of the viral segments of influenza H7N9 isolated from human patients. Using the software program Mega 6.02, phylogenetic trees were inferred by using the Maximum Likelihood method based on the General Time Reversible Model with 1000 bootstrap replications. Bootstrap support values \u226570% are shown. Branch lengths are proportional to number of substitutions per site. Unmarked strain names:", "Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers\nPassage: Arenaviruses have a bisegmented, negative-sense, single stranded RNA genome with a unique ambisense coding strategy that produces just four known proteins: a glycoprotein, a nucleoprotein , a matrix protein , and a polymerase . Of these proteins, the NP is the most abundant in virus-infected cells. Recombinant protein technology could meet the demand for a simple and reliable VHF test system, and recombinant NP has been shown to be useful for serological surveys of IgM-and IgG antibodies against arenaviruses . Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: Abstract: The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World and New World complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: Purified rNPs. The expression and purification efficiency of arenavirus rNP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after staining the gels with Coomassie blue. Purified NP antigens with approximate molecular weights of 62 kDa from Luna, LCM, Lassa, Lujo, Junin, Machupo, Guanarito, Sabia, and Chapare viruses and the purified negative control antigen are shown. Title: Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors", "Passage: Arenaviruses are enveloped, ambisense single-stranded RNA viruses. Their structure consists of a membrane envelope containing the surface glycoprotein subunits surrounding a capsid, which consists of the Z matrix protein . Inside the capsid are the L RNA-dependent RNA polymerase and the viral bi-segmented genome encapsulated by the nucleoprotein . Cell entry is mediated by GP, which is first expressed as the glycoprotein precursor complex . The host subtilase SK1-S1P proteolytically cleaves GPC into its three final subunits : GP1, GP2, and SSP , which form heterotrimers on the cell membrane surface . GP1 forms spikes protruding from the viral envelope", "Title: The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection\nPassage: and cytokines, such as interleukin-1\u03b2 , IL-6, IL-8, granulocyte-macrophage colony-stimulating factor , and tumor necrosis factor-\u03b1 are also produced. These molecules promote chemotaxis of the resident DCs toward virus-infected and dead cells. Neutrophils, monocytes, macrophages, plasma cells, mDCs, and pDCs also migrate from the blood vessels to the site of infection. IFN-\u03b3inducible protein 10 , monocyte chemotactic protein 1 , macrophage inflammatory protein-2 , MIP-3\u03b1, and MIP-3\u03b2 largely contribute to the transmigration of blood DCs. However, these blood-borne immune cells can also be infected by viruses, which can then modulate the production of various cytokines and chemokines. Title: Characteristics of human infection with avian influenza viruses and development of new antiviral agents", "Passage: Accumulating evidence suggests that virus-induced cytokine/chemokine dysregulation also plays a significant role in the pathogenesis of AIV infection . Respiratory epithelial cells and macrophages are the primary innate immune cells involved in AIV infection . Pronounced activation of the proinflammatory cytokine/chemokine cascade prolongs the period of inflammatory response and contributes to further tissue damage and the persistence of the systemic inflammatory response syndrome . Furthermore, cytokines can further sensitize neighboring cells by up-regulating RIG-I and amplifying the cytokine cascade in some HPAI infections . It appears that cytokine responses may be driven by highlevel viral replication, because plasma levels of Title: Innate Immune Sensing and Response to Influenza", "Passage: In addition to the initial IFN-mediated antiviral response, epithelial cells secrete various cytokines and chemokines such as IL-6, TNF-a, IL-8/CXCL8, CXCL10, CCL2, CCL5 . Furthermore, influenza virus-infected epithelial cells trigger recruitment of an array of innate immune cells, which participate in the protective immune response . Interestingly, a recent study in mice showed that expression of GM-CSF by influenza virus-infected alveolar epithelium is essential for effective viral clearance mediated by CD103 + DC-induced CD8 + T cells . Title: Innate Immune Response of Human Alveolar Macrophages during Influenza A Infection", "Passage: Chemokine and cytokine responses are required for protection of the host against viral infection. However, an exuberant response contributes to the influenza-induced morbidity and mortality, especially in severe pandemic and avian influenza infections . In the current study, PR/8 infection induced an increase in TNF-a and IL-1b, well-known paracrine proinflammatory factors. Therefore, we hypothesized that inhibiting these factors might reduce the influenza-induced-inflammatory response. Since the contemporary virus NY/238 induced a similar cytokine and chemokine response as PR/8, it would be reasonable to expect that the regulation of chemokine and cytokine in contemporary influenza infection might also be similar to PR/8", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: one pre-pneumococcal conjugate vaccination study, only 34% of children hospitalized with pneumonia had primary end-point pneumonia . A revised case definition of \"presumed bacterial pneumonia\" has been introduced, and this definition includes pneumonia cases with WHO-defined alveolar consolidation, as well as those with other abnormal chest radiograph infiltrates and a serum C-reactive protein of at least 40 mg/L . This definition has been shown to have greater sensitivity than the original WHO radiologic definition of primary end-point pneumonia for detecting the burden of pneumonia prevented by pneumococcal conjugate vaccination . Using the revised definition, the 10-valent pneumococcal conjugate vaccine , Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The WHO radiologic case definition was not intended to distinguish bacterial from viral etiology but rather to define a sub-set of pneumonia cases in which pneumococcal infection was considered more likely and to provide a set of standardized definitions through which researchers could achieve broad agreement in reporting chest radiographs. However, despite widespread field utilization, there are concerns regarding inter-observer repeatability. There has been good consensus for the description of lobar consolidation but significant disagreement on the description of patchy and perihilar infiltrates . In addition, many children with clinically severe lung disease do not have primary end-point pneumonia: in Title: Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study", "Passage: the \u0394 \u0394 Ct method using control RNU-44 and -48 as reference microRNAs. Total mRNA was purified from transfected and infected MDMs using the RNeasy kit and specific primers were used to amplify transforming growth factor beta-2 , SOCS6 41 43 , and 3) absence of wheezing at auscultation, and, 4) first symptoms appearing within the last 14 days, and 5) radiological confirmation of pneumonia as per WHO guidelines 44 . Based on these primary criteria defining pneumonia cases, all 74 cases were retrospectively re-evaluated according to the WHO \"Pocket book of hospital care for children\" 45 criteria to evaluate Title: Pneumonia in Bhutanese children: what we know, and what we need to know", "Passage: The clinical case definition of pneumonia has been changing over the last few decades . As of today, there is no optimal gold standard definition available . Lower respiratory infections is a broad term that includes pneumonia and bronchiolitis, as defined in the Global Burden of Diseases, Injuries, and Risk Factors Study . This is the terminology we strived to use in this review. However, we will report data as defined by the study authors. Thereby, ARI is often used and may imply here a broader concept including both upper and lower respiratory infections.", "Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study\nPassage: for other isolates in other time periods and other continents . The stalk region has therefore stayed unchanged and the two sequons seem to be conserved. Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study\nPassage: Our results support the suggestion that the evolution of influenza A viruses is more complex than originally believed . Local short term evolution of influenza virus is a stochastic process, also involving gene reassortments. It will be interesting to further investigate how viruses from other parts of Europe influence on the evolu-tion of Danish isolates when more full length sequences from Europe are made public. Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study", "Passage: The changes G186V and V226I increased egg viral replica-tion of A/Fujian/411/02 viruses so did the changes G186V and A196T for A/California/20/ 99 viruses . On the contrary, others have stated that the V226I change in combination with T155 and H156 do not result in viral recovery in eggs . This might explain the delay in the 2006-2007 vaccine production for the northern hemisphere due to egg propagation difficulties with the A/Wisconsin/67/05 strain. The influence on replication efficiency by the other substitutions observed at receptor binding sites should be investigated further. Title: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study", "Passage: three pandemics the last hundred years, the Spanish flu in 1918 , the Asian flu in 1957 and the Hong Kong flu in 1968 . It is believed that new pandemics emerge through shifts with strains from the avian reservoir, as was the case of the pandemics of 1957 and 1968, or by direct introduction of an avian strain into the human population as suggested for the 1918 pandemic . At present only two of the 16 possible HA subtypes , and two of the nine possible NA subtypes are circulating in man. H3N2 and H1N1 influenza A viruses have", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Lederberg et al. first pointed to the multiplicity of factors driving disease emergence, which later were elaborated and described in terms of 'the convergence model' . The model proposes emergence events are precipitated by the intensifying of biological, environmental, ecological, and socioeconomic drivers. Microbial \"adaptation and change,\" along with \"changing ecosystems\" and \"economic development and land use\" form major themes. Joshua Lederberg, the major intellectual force behind the studies summed-up saying \"Ecological instabilities arise from the ways we alter the physical and biological environment, the microbial and animal tenants of these environments, and our interactions with the parasites\" . Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: Lederberg et al. first pointed to the multiplicity of factors driving disease emergence, which later were elaborated and described in terms of 'the convergence model' . The model proposes emergence events are precipitated by the intensifying of biological, environmental, ecological, and socioeconomic drivers. Microbial \"adaptation and change,\" along with \"changing ecosystems\" and \"economic development and land use\" form major themes. Joshua Lederberg, the major intellectual force behind the studies summed-up saying \"Ecological instabilities arise from the ways we alter the physical and biological environment, the microbial and animal tenants of these environments, and our interactions with the parasites\" . Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: has demonstrated that the percentage of land under rice in peri-urban areas and rural areas is similar. Hence diseases associated with rice production are likely to peak in peri-urban areas given other risk factors such as land-use diversity, CTI, and distance to infrastructure. Our poultry flock-size diversity findings may also be relevant to understanding the dynamics of other poultry related infections such as Newcastle disease. Finally, these results suggest the validity of a general model of zoonotic disease emergence that integrates IOM's convergence model with the subsequently proposed social-ecological systems and EID framework. Thus, convergence represents the coalescence in time Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: has demonstrated that the percentage of land under rice in peri-urban areas and rural areas is similar. Hence diseases associated with rice production are likely to peak in peri-urban areas given other risk factors such as land-use diversity, CTI, and distance to infrastructure. Our poultry flock-size diversity findings may also be relevant to understanding the dynamics of other poultry related infections such as Newcastle disease. Finally, these results suggest the validity of a general model of zoonotic disease emergence that integrates IOM's convergence model with the subsequently proposed social-ecological systems and EID framework. Thus, convergence represents the coalescence in time", "Title: One family cluster of avian influenza A(H7N9) virus infection in Shandong, China\nPassage: The first case of human infection with a novel reassortant avian influenza A virus was identified in Shanghai and Anhui of China during February and March 2013 . Since this H7N9 virus was not detected in humans or animals previously, the situation raises many urgent questions and global public health concerns. The H7N9 virus infections have extended to 12 provinces infected 134 patients and killed 45 people in China as of September 30, 2013 . In most of the laboratory confirmed cases the patients developed severe pneumonia and acute respiratory distress syndrome and needed intensive care . Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: In February 2013, China detected the first human cases of H7N9 infection in severely ill patients with pneumonia. 3 As of May 22, 2014 , there have been 446 confirmed H7N9 cases in China resulting in 163 deaths. 4 The cases have occurred mainly during two waves 2013 and week 40, 2013week 20, 2014) , 4 of which 85% had prior exposure to poultry or contaminated live poultry markets. The median time from poultry exposure to disease onset was 5 days, whereas the median time from illness onset to hospital admission, ARDS development, antiviral therapy and death was 5, 6\u00c18, Title: Early responses to H7N9 in southern Mainland China", "Passage: Avian influenza A H7N9 was first identified as a novel virus in China on 1 st April 2013 . While several variants of highly pathogenic avian influenza have been reported worldwide, poor management and initial denial of SARS in China made the H7H9 outbreak of particular concern . During SARS the Chinese government kept the new outbreak secret, downplaying its emergence and treating it as a local issue best left to local bureaucracy . Communication between provincial localities and bureaucratic departments was poor, and a lack of formal organisation meant poor provision of public health information, partly as a result Title: A family cluster of three confirmed cases infected with avian influenza A (H7N9) virus in Zhejiang Province of China", "Passage: Human infection with avian influenza A/H7N9 virus was first identified in March 31 of 2013, in China, a total of 453 confirmed cases were found in the world up to date . The seasonal epidemiology is characterized to occur from November through April in China, coinciding well with both seasonal human influenza and H5N1 in birds . Almost all cases were hospitalized, and 1/3 of cases died. The fatality is much higher than that for seasonal influenza in the China , but it is lower than for cases of H5N1 . Current evidence suggests that human infection appears to be", "Title: Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life\nPassage: IFN-I signaling in the shaping of the infant viral pattern. In accordance with the role of IFN-I on T cell clonal expansion , this viral pattern was mirrored by the frequencies of IFN-\u03b3-producing LCMV-specific CD8 + T cells which were similarly reduced in 2-week-old WT, 2-week-old IFNAR -/-and adult IFNAR -/-mice on day 10 . CD4 + T cell responses showed a comparable deficit . Thus, the limited early life IFN-\u03b1 responses were associated to a similar pattern of impaired viral control / limited T cell responses as in adult IFNAR -/-mice. Title: Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life", "Passage: Almost each virally infected cell may produce IFN-I in response to dsRNA, DNA, or viral nucleocapsids. However, pDCs are the earliest source of IFN-I in many viral infections . pDCs were identified as the only source of the Day 1 peak of IFN-\u03b1 during adult LCMV-Armstrong infection , DCs and infected cells contributing to Day 2-3 levels . The failure of 2-week-old mice to generate early adult-like IFN-I responses to LCMV-WE reflects the specific pattern of their pDC responses. First, IFN-\u03b1 titers were low on Day 1 but reached adult levels on Day 2, before declining on Day 3, probably Title: Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life", "Passage: To define whether the limitation of early life IFN-I responses were sufficient to explain alone the early life patterns of CD4/CD8 T cell responses and viral control, we compared viral titers and T cell responses in LCMV-infected 2-week-old vs. adult wild-type or IFN-I receptor-deficient mice. On day 10, splenic LCMV titers had already declined to very low levels in adult WT mice. In contrast, they persisted at similarly high titers in adult and infant IFNAR -/-as in WT infant mice. Slightly lower but statistically similar titers were observed in adult and infant IFNAR -/-mice , suggesting a main role of Title: Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life", "Passage: these findings suggest that the limited immediate-early production of IFN-I by infant mice is insufficient to control early viral replication. Remarkably, the viral and immunological impacts of a transient delay in IFN-\u03b1 release in infant mice were as severe as those resulting from the total absence of IFN-\u03b1 signaling ). This may reflect the subsequent influence of higher levels of LCMV NP, which inhibit IFN-I production by infected cells and thus terminate IFN-I responses, as serum IFN-I titers declined faster in infant mice. Thus, IFN-\u03b1 is required before the peak of viral replication, a pattern successfully elicited by adult but", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Empyema is a rare complication of pneumonia. An increased incidence of empyema in children was noted in some high-income countries following pneumococcal conjugate vaccination-7 introduction, and this was attributed to pneumococcal serotypes not included in pneumococcal conjugate vaccination-7, especially 3 and 19A . In the United States, evidence from a national hospital database suggests that the incidence of empyema increased 1.9-fold between 1996 and 2008 . In Australia, the incidence rate ratio increased by 1.4 times when comparing the pre-pneumococcal conjugate vaccination-7 period to the post-pneumococcal conjugate vaccination-7 period . In Scotland, incidence of empyema in children rose from 6.5 Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: per million between 1981 and 1998, to 66 per million in 2005 . These trends have been reversed since the introduction of pneumococcal conjugate vaccination-13. Data from the United States suggest that empyema decreased by 50% in children younger than 5 years ; similarly, data from the United Kingdom and Scotland showed substantial reduction in pediatric empyema following pneumococcal conjugate vaccination-13 introduction . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: states, population-based incidence rates are higher than at any time in the last 70 years . In contrast, most low-and middleincome countries use whole-cell pertussis vaccines and the numbers of pertussis cases in those countries were stable or decreasing until 2015 . However recent evidence from South Africa shows an appreciable incidence of pertussis among infants presenting with acute pneumonia: 2% of clinical pneumonia cases among infants enrolled in a birth cohort were caused by pertussis , and 3.7% of infants and young children presenting to a tertiary academic hospital had evidence of pertussis infection . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: Another etiology is pertussis. In the last decade there has also been a resurgence in pertussis cases, especially in highincome countries . Because pertussis immunity after acellular pertussis vaccination is less long-lasting than immunity after wild-type infection or whole-cell vaccination, many women of child-bearing age have waning pertussis antibody levels. Their infants might therefore be born with low transplacental anti-pertussis immunoglobulin G levels, making them susceptible to pertussis infection before completion of the primary vaccination series . In 2014, more than 40,000 pertussis cases were reported to the Centers for Disease Control and Prevention in the United States; in some", "Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus\nPassage: Another difference between the 2 systems is the threshold relationship between species diversity and SNV prevalence, which suggests that the shape of the dilution curve may be mechanism dependent and is the reason we proposed the term \"zoonotic release.\" Given that many hantaviruses are hosted by generalist rodent species that dominate ecosystems as species diversity decreases . Additionally, at all parks deer mouse density increased but infection prevalence did not, clearly indicating that density is not the sole driver of infection prevalence in this system. A logistic regression with both density and mammal species diversity in the model showed similar Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus", "Passage: Although only 5 sites were examined, the intensity of the sampling yielded a total of 5,057 individuals from 21 species, resulting in a thorough species inventory over a gradient of diversity in small mammal ecological communities. Deer mice averaged 62% of all captures and were the dominant species at all sites. Mammal species diversity differed significantly among sites , except sites 3 and 4 . Densities varied spatially and temporally; all parks exhibited the highest densities during year 2 . Interannual variances of densities were large due to seasonal differences in capture rates, such that no statistical differences in densities Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus", "Passage: D uring the past 60 years, the number of emerging pathogens affecting humans has substantially increased . Of these emerging infectious diseases, 62% are zoonotic , meaning they are naturally hosted by, and persist in, wildlife but also affect human populations. The ecological factors associated with zoonotic disease emergence are likely complex and are poorly understood. Most often, because of limited time, resources, and the exigencies of the situation, outbreak investigations of emerging diseases seek only to discover the pathogen responsible for the disease in humans. But ecological studies are of critical importance to long-term containment of zoonotic disease emergence; Title: Increased Host Species Diversity and Decreased Prevalence of Sin Nombre Virus", "Passage: Using nonlinear regression, we found a significant negative relationship between infection prevalence and mammal species diversity. Infection prevalence increased as diversity decreased, up to an inflection point where the rate of infection increased exponentially . No regression model was able to account for the association between infection prevalence and density of deer mice, either alone or with species diversity in the model.", "Title: Markers of exacerbation severity in chronic obstructive pulmonary disease\nPassage: Finally, the compatibility between the studies of COPD exacerbation that we analysed may have been limited by substantial variations in the time and location of studies. Exacerbations are more likely in summer but many studies failed to report the time of year or the time period for study implementation. Thus, seasonal effects, combined with the low incidence of exacerbations per patient, could represent an inherent bias. In addition, different institutions probably had different standards with respect to diagnosis and management of COPD exacerbations when these studies were performed. Such variations may also explain any observed inconsistencies in our findings. However, Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: We were also aware that the clinical studies we analysed differed with respect to which comorbidities or identifiable causes for exacerbations were reported. Most patients were elderly and therefore were more likely to be suffering from one or more co-existing diseases such as asthma or cardiovascular disease. Such co-morbidity makes interpretation of our findings more difficult with respect to the true causes of exacerbations. If their aetiology could be determined, then susceptible patients such as those in Level I could be identified and new treatments developed to help prevent their onset and related hospital costs.", "Title: Disease ecology and the global emergence of zoonotic pathogens\nPassage: The continual expansion of human populations since prehistoric times, and particularly since the advent of settled agriculture with its associated domesticated animals exposing humans to their pathogens as well as those spilling over from wild animal populations, has incrementally added to the pathogen load through successive invasions by different organisms over time . Well established principles of population ecology, applied via mathematical epidemiology as Anderson and May and others so aptly have done, readily explain why, ceteris paribus, infectious disease incidence should generally be increasing with human population size, as it has in the world's poorest and most populous regions. Title: Disease ecology and the global emergence of zoonotic pathogens", "Passage: increased contact with and transport of wildlife , and increased ruralurban transport and concentration of wild species for the exotic food market , is another contributor to increasing disease emergence. It can be assumed these impacts on wildlife populations also contribute to changes in the composition of ecological communities on a regional scale , and often result in a hyper-abundance of small mammal species low in the food chain, which are likely to serve as human disease reservoirs. Similar effects of ecological disruption appear to generally apply to invertebrate commu- Whether a disease 'jumps' to the regional population and the Title: Disease ecology and the global emergence of zoonotic pathogens", "Passage: Another consequence of the dramatically increased densities of humans, host reservoirs, and vectors is the increased number of pathogen genomes. The resulting increased levels of genetic variability can accelerate microbial adaptation, including evolution of pathogenesis, and antimicrobial resistance. Genetic variability increases with population size and density through a variety mechanisms including mutation. The probability of producing more virulent variants not only increases with host population size but also with crowding and co-mingling of different host species . In general, parasite -host relations naturally constitute a co-adaptive/ evolutionary 'dance' along the pathogenicity threshold, which is likely to be crossed with greater Title: Disease ecology and the global emergence of zoonotic pathogens", "Passage: Population ecology, genetics and disease emergence Of particular relevance to disease emergence is the explanation provided by theoretical population biology, already mentioned, of how host population size determines whether or not a pathogen can persist in a population. The accumulated findings demonstrate thresholds exist, depending on the type of pathogen and host population, below which a pathogen cannot be sustained. Considered in light of the exponentially increasing size of human and domestic host and vector populations in the world, the breaching of thresholds of pathogen persistence can explain much of the increase in emerging infectious diseases.", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: role of the RNA methylation machinery in controlling inflammatory mRNA stability. These activities take place in various subcellular compartments and are differentially regulated during infection. In this way, mRNA-destabilising RBPs constitute a 'brake' on the immune system, which may ultimately be toggled therapeutically. I anticipate continued efforts in this area will lead to new methods of regaining control over inflammation in autoimmunity, selectively enhancing immunity in immunotherapy, and modulating RNA synthesis and virus replication during infection. Title: Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast", "Passage: In a prior proof-of-principle experiment, we utilized the well characterized \u00c01 PRF signal from the yeast L-A dsRNA virus to demonstrate that these elements can generally function as mRNA destabilizing elements through the NMD pathway . Subsequently, a bioinformatics approach was used to determine that potential \u00c01 RF signals are widely found in all genomes examined, and that the great majority of these are predicted to direct elongating ribosomes to premature termination codons . Here, we show that these chromosomally encoded, endogenous \u00c01 RF signals can also function as cis-acting mRNA destabilizing elements, both in the context of a reporter Title: Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast", "Passage: used to delve deeper into the relationships between \u00c01 RF and mRNA stability. The EST2 mRNA is destabilized by \u00c01 RF primarily via NMD. Ablation of its five \u00c01 RF signals resulted in stabilization of the EST2 mRNA, and an inverse correlation between \u00c01 RF efficiency and EST2 mRNA steady-steady state abundance was observed. Title: Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast", "Passage: mRNA, and also in one case in a natural context. Further, we demonstrated that \u00c01 RF signals can differentially affect mRNA abundance through the NMD pathway, and the data are also consistent with destabilization through NGD. These are modeled in Figure 5 . In support of this idea, the EST2, BUB3 and SPR6 mRNAs were all stabilized in upf1D, upd2D/nmd2D, upf3D, dcp1D and xrn1D cells , and the half-lives of these mRNAs were less than the mean in wild-type cells . Interestingly, TBF1 is not represented in these databases. In the case of a ribosome shifting reading frame into a", "Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: There were four potential limitations to our study. First, we only conducted a cross-sectional study in Study 3, whereas it would be preferable to measure Chikui likelihood earlier and then track the material and mental benefit of our participants years later. In the absence of a longitudinal study, our findings are suggestive but do not prove causality, and the following two questions therefore remain unaddressed: we are unable to confirm whether the correlation found in Study 2 means that it is the belief that boosts both financial and psychological well-being, rather than the reverse . Only a longitudinal study can Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: A classic human study found that, in donors lacking neutralizing antibodies, pre-existing cytotoxic T-cell levels against influenza correlated with reduced virus shedding but not reduced symptoms after influenza virus challenge . Epidemiological studies of the 1957 pandemic, an H1N1 to H2N2 shift, suggested cross-protection, but these studies were too small for statistical significance or lacked laboratory confirmation of self-reported symptoms . A human challenge study found a correlation of CD4 memory with reduced illness duration, viral shedding, and symptom severity . Title: The Trojan Chicken Study, Minnesota", "Passage: Some of our study findings were unanticipated. We expected contamination proportions to vary by age, gender, and role because we expected these factors to affect the amount of contact with birds and handwashing behavior. However the rates did not vary by these variables. This finding could be due to the study's limited power to detect such differences. If the differences between those exposed and those unexposed were statistically significant , they might be consistent with studies that suggest that animal handlers practice better hygiene compared to nonhandlers in the same environment. Alternatively, animal handlers may engage in other behavior that Title: Chinese journals: a guide for epidemiologists", "Passage: results. However, subsequent studies found little evidence supporting this assertion. Pham et al. found that language bias led to an under-estimation of the protective effect of intervention in RCTs in complementary and alternative medicine systematic reviews but not in that of conventional medicine .", "Title: Estimating the number of infections and the impact of non-\nPassage: Public events banned: This refers to banning all public events of more than 100 participants such as Title: Estimating the number of infections and the impact of non-\nPassage: banned The government bans all public events.39 9/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: banned The government bans events >100 people.52 13/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: banned The government bans events >500 people.49 12/3/2020", "Title: Near-Patient Sampling to Assist Infection Control\u2014A Case Report and Discussion\nPassage: L and a respiratory rate of 12-16 breaths per minute , which gives a total inhaled volume of approximately 180-336 L over 30 min, depending on their activity level. Title: Exhaled breath condensate sampling is not a new method for detection of respiratory viruses", "Passage: be due to the low number of participants subjects were included . Remarkably, the studies reporting this higher detection rate used collections masks, while the study using the RTube\u2122 reported comparable findings. Face masks consist of electret which trap viruses based on permanently charged fibres . In addition, the Teflon filter has 2 \u03bcm pores which will retain all larger particles. Possibly, the lower detection rate can partly be explained by the fact that the RTube\u2122 is manufactured in polypropylene and does not possess a virus attracting and filtering feature like the aforementioned materials. Title: Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method", "Passage: of sample . The RTube eliminates the first 3 steps, but each collection still requires 10 min and costs $23.25 compared to 31 min and $47.17 per collection for the EcoScreen. These collection devices are generally expensive, e.g., the EcoScreen costs around $9000. A recent study compared the sampling efficiency of the Rtube with that of throat swab method, showing detection rates of 7% and 46.8% for the Rtube and the throat swab method, respectively . It was suggested that the RTube is not applicable for viral detection in exhaled breath . In addition, condenser coatings , sampling temperature and Title: Composition and dynamics of the respiratory tract microbiome in intubated patients", "Passage: Fifteen subjects were enrolled from the medical intensive care unit of the Hospital of the University of Pennsylvania. Initial sample and data collection was performed within 24 h of intubation, with subsequent collection performed at 48-to 72-h intervals thereafter for the duration of mechanical ventilation. Sampling was performed by oropharyngeal swab and endotracheal aspirate. Informed consent was obtained from subjects themselves or a patient surrogate. The protocol was reviewed and approved by the University of Pennsylvania IRB . Healthy controls were non-intubated volunteers without underlying lung disease sampled by OP swab and bronchoscopic bronchoalveolar lavage and have been previously described", "Title: Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators\nPassage: In multivariate analysis, light smokers = 2.0, 95%CI: 1.42.8, P < 0.01], medium smokers and heavy smokers were more likely to be vaccinated compared to not smokers. Moreover, those who had malignancy and those who suffered from immunosuppressive conditions were more likely to receive influenza vaccine compared to individuals who did not suffer from these conditions . Title: Seasonal influenza risk in hospital healthcare workers is more strongly associated with household than occupational exposures: results from a prospective cohort study in Berlin, Germany, 2006/07\nPassage: symptoms due to non-infectious causes may be over-reported in non-smokers. Title: COVID-19 and smoking: A systematic review of the evidence", "Passage: We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases 12 . However, from their published data we can calculate that the smokers were 1.4 times more likely to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers . Title: COVID-19 and smoking: A systematic review of the evidence", "Passage: disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases. Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases. Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak. Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients\u2019", "Title: Influenza virus-related critical illness: prevention, diagnosis, treatment\nPassage: Persons with uncomplicated influenza typically experience acute onset of respiratory symptoms , myalgias, and headache with or without fever. During influenza season, clinicians should also consider influenza when there is only fever present or in patients who are afebrile and have respiratory symptoms . Complications of influenza vary by age, underlying comorbidities or high-risk conditions such as pregnancy, and immune function; elderly and immunocompromised persons may not always manifest fever. Critically ill patients may be admitted with respiratory or multi-organ failure, exacerbation of an underlying condition such as chronic lung disease , heart failure , or other extrapulmonary complications including Title: Clinical review: Primary influenza viral pneumonia", "Passage: Bacterial co-infection, though uncommonly reported in the early stages of the 2009 H1N1 pandemic, may be more prevalent than initially thought. A recent analysis of lung specimens from 77 fatal cases of pandemic H1N1v 2009 infection found a prevalence of concurrent bacterial pneumonia in 29% of these patients . The most common coinfecting bacterial pathogens were pneumococcus, Staphylococcus aureus, and Streptococcus pyogenes, with a median duration of illness of 6 days . Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts", "Passage: group. Most had some form of graft-vs-host disease . Those who did not undergo HSCT were undergoing immunosuppressive therapy . In the nonimmunocompromised group 17 patients had chronic comorbidities including hypertension, diabetes mellitus, coronary artery disease, asthma or chronic obstructive pulmonary disease, or well-controlled HIV infection. A full symptom evaluation at the time of diagnosis was performed in 80 of 86 patients . The most common symptoms noted were dry cough , fever , and headache . Chills, coryza, productive cough, and sweats were also common. A range of other symptoms were observed including shortness of breath and chest pain. Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features", "Passage: Other complications that have been reported include myocarditis, pericarditis, encephalitis, seizures, myositis, multiorgan failure and toxic shock syndrome . The mortality in this group has been found to be around 18% with older age, requirement of mechanical ventilation and co-morbid conditions being major risk factors. A large number of deaths are seen in young to middle aged adults due to the higher incidence in this group .", "Title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling\nPassage: The weekly proportion of tests confirmed positive for influenza peaked each season at 15 to 30%. Accounting for the model estimated false negative rate suggests that during periods of peak influenza activity, 40-90% of tests were performed on specimens taken from persons recently infected with influenza. Influenza was confirmed in only 14% of specimens sent for testing over the winter period, whereas the sensitivity estimate would imply that up to 40% of influenza tests could be attributed to an influenza infection. The corresponding figures for the whole year indicate that 10% of specimens were confirmed positive for influenza and 30% Title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling", "Passage: Over 50,000 tests for influenza were reported to the RVDSS each year, peaking in 2004/05 at 101,000. Overall 10% of the influenza tests were positive for influenza, ranging from 4% to 13% depending on the season. The proportion positive for RSV, parainfluenza and adenovirus averaged 9%, 3% and 2% respectively. As seen in Figure 1 , no virus was identified in 75% of specimens submitted for testing . Even for the winter months of December through April, one of these 4 viruses was identified on average in no more than 30% of the specimens. The strong and consistent synchronization of Title: The performance of interferon-gamma release assay in nontuberculous mycobacterial diseases: a retrospective study in China", "Passage: The total positivity of T-SPOT.TB was 53.4% among the NTM group . For probable cases, the T-SPOT.TB assay was positive in 53.5% ; for definite cases, 16 of 30 definite cases were positive; there was no statistical difference in the positivity rate between them . For NTM strains, 47.1% of Mycobacterium intracellulare cases were positive on T-SPOT.TB assay ; 70% of Mycobacterium chelonae cases were T-SPOT.TB positive ; 57.1% of Mycobacterium fortuitum cases were T-SPOT.TB positive . Title: Private collection: high correlation of sample collection and patient admission date in clinical microbiological testing complicates sharing of phylodynamic metadata", "Passage: Virology test coding did not permit ready identification of only positive test results. To check the impact of examining all virus testing versus only viral positives, we extracted 16,434 unique samples for which the test results field either contained 'positive' or a quantity. In this subset, 14,133 of samples were collected on the same day as the admission date and 14,994 of the samples were collected within 1 day of admission. The distribution of this subset of viral positives was significantly different compared with all virus testing . A likely explanation for this phenomena is the increased prevalence of positive", "Title: A Computer-Aided Detection System for Digital Chest Radiographs\nPassage: small number of images available poses an additional challenge. To get a sample of all possible variations of sex, age, pathologies, and so forth, some thousands of radiographs would be necessary. For example, some classifiers in Table 1 produce better results with the complete set than with only the male/female set. There is not a method clearly yielding the best accuracy for all the tests, although voting schemes, DV and CV, usually obtain less error rates. Figure 7 shows that the correct selection of the threshold, specially in CV method, can affect greatly its effectiveness. In CV, the optimum threshold Title: Enhancing Time-Series Detection Algorithms for Automated Biosurveillance", "Passage: be detected. Using this method, a single computer run can calculate sensitivity for detecting single-day additional counts on all days in the dataset; if the additional counts are spread over multiple days, separate computer runs would be needed . Title: A Computer-Aided Detection System for Digital Chest Radiographs\nPassage: We were also interested in studying the effect of the threshold in the voting methods. Figure 7 shows a graphical comparison of the three classifiers, with and without weighting matrix, using different thresholds for DV and CV methods. Title: Rapid detection of pandemic influenza in the presence of seasonal influenza\nPassage: comparisons with other methods.", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Comparing the outcomes of different postgraduate year training programs in Taiwan", "Passage: This study revealed no significant differences in medical knowledge and clinical performance among the four groups of trainees regardless of program, and showed that the learning results persisted long after the training ended if the programs were well-designed. The weaknesses of the study consisted of the limited number of stations that the trainees participated in during the clinical performance evaluation and possibly the high-quality MCQ items; however, the results still provide valuable information that can be used to improve the design of the training program such as arranging more core competencies in the 1-year program. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China\nPassage: case the patient load exceeds the hospital capability of the IDH, new IDHs should be considered either by building a temporary new IDH or reconstructing an existing hospital. Wuhan, the epicenter of the outbreak, is racing against time to build two specialized hospitals for nCoV patients, namely Huoshenshan and Leishenshan hospital, whereas a different strategy has been undertaken in Shenzhen city by reconstructing an existing hospital to become an IDH with capability of 800 beds. Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: development and a candidate vaccine was ready for initial laboratory testing. Currently Chinese health authorities are building a 1000 bed hospital in Wuhan in 10 days. Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China", "Passage: Date: 2020 Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: emergencies. On the same day, our hospital was designated to care for Sichuan province", "Title: Clinical vaccine development\nPassage: example . These kinds of vaccines brought dramatic improvement in vaccine safety, mitigating the risk of using purified inactivated antigens obtained from infected patients. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: replication, immunity, and disease. There is also a need for revision of the current influenza virus vaccine strategies for at-risk populations, particularly those at either end of the age spectrum. An example of an improved vaccine regime might include the use of a vectored influenza virus vaccine that expresses the HA, NA and M and/or NP proteins for the two currently circulating influenza A subtypes and both influenza B strains so that vaccine take and vaccine antigen levels are not an issue in inducing protective immunity. Recombinant live-attenuated or replication-deficient influenza viruses may offer an advantage for this and other Title: Interplay between cost and effectiveness in influenza vaccine uptake: a vaccination game approach\nPassage: relatively better protection. Title: Vaccines for the future: learning from human immunology", "Passage: Vaccination has been one of the most effective measures to control infectious diseases in the 20th century. It is believed that vaccination saves 2-3 million lives per year globally. Smallpox has been eradicated worldwide and polio is almost eliminated. Most of the viral and bacterial diseases traditionally affecting childhood all over the world are now preventable with vaccines and hepatitis B virus , which in some cases cause cancer. In summary vaccination has been -and continues to represent -a success story . However, there is still a long list of viruses , human immunodeficiency virus , Dengue, respiratory syncytial virus", "Title: Influenza, evolution, and the next pandemic\nPassage: In outbreaks of seasonal and pandemic influenza, only a small number of individuals who are infected develop severe or fatal illness. This was true during the 1918 pandemic; although approximately one-third of the human population was infected, only a small proportion died. Some of this protection is due to CD8 + T-cell immunity, especially immunity directed against the evolutionarily conserved NP antigen . This immunity reflects previous exposure of populations to influenza virus antigens, but importantly it encompasses both Group 1 and Group 2 viruses, unlike antigenic imprinting discussed above. T-cell immunity does not prevent the occurrence of infection, but Title: A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve", "Passage: animal influenza viral genomes can yield viruses with novel antigenic characteristics that would not be susceptible to human population immunity elicited by seasonal viruses. Human-to-human transmission of such viruses lead to occasional worldwide pandemics 8 . The recent outbreak of avian H7N9 influenza virus in China has resulted in a total of 681 laboratoryconfirmed cases and at least 275 deaths reported to WHO, posing a rapidly growing pandemic threat to public health 11 . Title: Conserved epitopes of influenza A virus inducing protective immunity and their prospects for universal vaccine development", "Passage: Influenza remains a serious respiratory disease in spite of the availability of antivirals and inactivated trivalent vaccines, which are effective for most recipients. Influenza viruses are RNA viruses with strongly immunogenic surface proteins, especially the hemagglutinin. Error-prone RNA-dependent RNA polymerase and segmented genome enable influenza viruses to undergo minor as well as major antigenic changes, which permit the virus to evade adaptive immune response in a variety of mammalian and avian species, including humans. The unpredictable variability of influenza A viruses, which cause yearly epidemics in human population, is the main reason why no effective prevention against influenza infection exists Title: Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment", "Passage: In summary, we find that levels of population immunity to H2 subtype viruses are not substantial enough to block epidemic spread of an H2 virus that had acquired efficient transmissibility between humans. Furthermore, the existing levels of population immunity to H2 viruses will continue to decline with new birth cohorts being added to the human population. Given that human-adapted H2N2 viruses that arose subsequent to the 1957 pandemic are present in many laboratories worldwide, these findings support the need to have preparedness for H2 viruses as a credible pandemic threat. The approach used in the case study of H2 viruses", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: In addition to the effect on radiologic pneumonia, pneumococcal conjugate vaccination reduces the risk of hospitalization from viral-associated pneumonia, probably by reducing bacterial-viral co-infections resulting in severe disease and hospitalization . An analysis of ecological and observational studies of pneumonia incidence in different age groups soon after introduction of pneumococcal conjugate vaccination-7 in Canada, Italy, Australia, Poland and the United States showed decreases in all-cause pneumonia hospitalizations ranging from 15% to 65% . In the United States after pneumococcal conjugate vaccination-13 replaced pneumococcal conjugate vaccination-7, there was a further 17% decrease in hospitalizations for pneumonia among children eligible for the Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: had a vaccine efficacy of 22% in preventing presumed bacterial pneumonia in young children in South America , and pneumococcal conjugate vaccination-13 had a vaccine efficacy of 39% in preventing presumed bacterial pneumonia in children older than 16 weeks who were not infected with human immunodeficiency virus in South Africa . Thus there is convincing evidence that pneumococcal conjugate vaccination decreases the incidence of radiologic pneumonia; however there is no evidence to suggest that pneumococcal conjugate vaccination modifies the radiologic appearance of pneumococcal pneumonia. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: vaccination, and a further 12% decrease among unvaccinated adults . Title: Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting", "Passage: 80% reduction or the lowest proportion of 40% reduction is achieved on the black and blue lines respectively. The uncertainty and sensitivity results demonstrate that there is considerable variability in the potential effectiveness of a vaccination programme when both parameter and structural uncertainty are included. Given available information, the impact of 70% coverage could be to reduce hospitalisations by any value between 10% and 90%, although the best median values are >60%. However, the age of optimum immunisation is robust to these uncertainties. Whether the objective is to maximise the chances of a very successful intervention , reduce the chances", "Title: DNA Vaccines\u2014How Far From Clinical Use?\nPassage: Nano-carriers offer the advantage to shield the DNA vaccine from degradation by DNases and other enzymes . Surface modifications of NC with moieties like antibodies or natural ligands like carbohydrates may enable direct targeting of DC . As outlined above, direct transfection of APC would prevent unwanted uptake of antigen and adjuvant by MDSC and TAM that promote tumor tolerance . In addition, internal expression of the transgene ensures that sufficient amounts of antigen are presented via MHCI to yield robust CD8 + T cell responses . Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: Taken together, these data support the notion that the exposition of the virus capsid proteins facilitates the immune response against the encoded antigen. Optimization of PEGylation chemistries and/or densities on adenovirus-based vaccine that promote and strengthen protective immune responses following oral immunization is currently underway. Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: carrier. Title: Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers", "Passage: confirming the brick-shaped morphology and size expected of the MVA vector, as described elsewhere . The expression of the ZIKV immunogens was confirmed by western blot in cells extracts from MVA-ZIKV-transduced BHK21 cells; using an anti-ZIKV E primary antibody . Taken together, we showed that MVA viral vectors are correctly packaged, carrying the ZIKV transgenes in their genome and more importantly, that they are capable of inducing the expression of the ZIKV E in transduced cells.", "Title: Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia\nPassage: the course of illness. Although immunomodulatory treatment has potential benefits at this stage, the focus of clinical management should be on preventing the intense cytokine response by early diagnosis and effective antiviral treatment. Title: Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia", "Passage: a Plasma levels of chemokines and cytokines in H5N1 patients were all higher than in healthy controls at o0.001 significance levels. b Comparison between H5N1 and H3/H1 patients. c Comparison between H3/H1 patients and healthy controls. und., undetectable. epithelial cells 22 . Plasma levels of other cytokines were not higher than healthy controls, although low levels of TNF-a, IL-1b and IL-12 were observed in four H5N1-infected individuals . Although levels of cytokines in lung tissue may be more relevant to pathogenesis than levels in blood 25 , it is likely that blood cytokine levels reflect the events in the highly Title: Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia", "Passage: Measurement of cytokines in plasma revealed elevated levels of IL-10, IL-6 and IFN-g in H5N1-infected individuals ; the latter is a strong inducer of IP-10 and MIG expression by bronchial Levels of chemokines and cytokines in the peripheral blood of patients with influenza H5N1 and H3N2 or H1N1. Levels are given as median log 10 pg per ml . Title: Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia\nPassage: vascular lung. In vitro infection of bronchial epithelial cells and macrophages with H5N1 viruses is associated with hyperinduction of chemokines and cytokines, suggesting that intrinsic viral properties may contribute to the increased levels and to pathogenesis. However, plasma levels of IP10, MCP-1, IL-8, IL-6 and IL-10 in our subjects correlated with pharyngeal H5N1 load , which indicates that the observed hypercytokinemia and hyperchemokinemia reflect, at least partly, increased viral replication.", "Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics\nPassage: Symptoms are common to each infection and manifest on a gradient. Generally, but far from always, influenza infection is more likely to result in a patient feeling so unwell as to take to their bed and have a fever, than RSV, an HRV, CoV or other common cold virus infection, during which daily life is usually less impacted. Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Human challenge studies with HRV have been shown to produce infection in over 90% of serologically susceptible subjects and result in a clinical syndrome that is comparable to that reported with natural colds . Symptoms usually appear within 24 hours and peak at 48-72 hours after inoculation. Virus shedding follows a pattern similar to that of their symptoms. In recent times, several hundred inoculations of adult subjects have been reported and have established this as a safe and effective method in which to study HRV-related disease in both healthy and asthmatic subjects . Title: Influenza, evolution, and the next pandemic", "Passage: Infection with influenza viruses initially targets respiratory epithelial cells . In response, myeloid and lymphoid cells mount a brisk pro-inflammatory response, often called a 'cytokine storm'. Patients who develop severe illness are unable to control what becomes a systemically dysregulated immune response. After several days , they develop evidence of immunosuppression . Death occurs in those who are unable to resolve their illness and restore homeostasis. Title: Influenza, evolution, and the next pandemic", "Passage: The importance of these post-infection variations was demonstrated in 25 HA-seronegative healthy young adults who were experimentally infected with influenza H3N2 virus . .) Following infection, peripheral blood cytokine responses were determined every six hours for the next five days. In nine subjects who developed symptomatic illness, there were early increases in cytokines associated with fever, leucocyte recruitment and markers of innate antiviral immunity, and some of these increases appeared as early as two days before the onset of symptoms . These cytokine findings were also demonstrated in a parallel genomic analysis. In contrast, the 17 subjects who remained asymptomatic", "Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: Spain 15% Title: Estimating the number of infections and the impact of non-\nPassage: 45. Wikipedia. 2020 coronavirus pandemic in Spain. Wikimedia Foundation Title: Estimating the number of infections and the impact of non-\nPassage: Spain measures cough or fever symptoms.47 17/3/2020", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: Text: An outbreak of novel coronavirus disease has occurred on a cruise ship, the Diamond Princess . The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: total of 3711 persons , 199 symptomatic cases have been diagnosed on board as of 24 February, and additional asymptomatic infections and symptomatic cases after disembarkation have also been reported. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: I analyzed the epidemic curve, ct, on day t, illustrated by the number of confirmed cases by the date of illness onset. The confirmatory diagnosis was made, using the reverse transcriptase polymerase chain reaction . The date of illness onset was defined as the first date of fever. In addition to the date of illness onset, cases were classified by contact history inside the cabin and also by the type of membership, i.e., crew or passenger. Close contact was defined as having at least one cabinmate who was confirmed by RT-PCR. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020", "Title: Human adenovirus type 7 infection causes a more severe disease than type 3\nPassage: Imaging and laboratory data on admission and during hospitalization were collected. White blood cell count > 15,000/ \u03bcL was defined as leukocytosis, whereas that < 4000/\u03bcL was defined as leukopenia. Title: Human adenovirus type 7 infection causes a more severe disease than type 3\nPassage: Laboratory findings for the HAdV-7-positive inpatients were also significantly different from those infected by HAdV-3 . Specifically, the HAdV-7-positive inpatients had lower white blood cell count , platelet count . In contrast, hemoglobin and C-reactive protein levels, and the percentages of lymphocytes, neutrophils and positive sputum culture were found to be statistically similar. Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: cells was counted under a microscope. The cells were centrifuged, smeared onto slides, fixed, and stained with Diff Quik to analyze and classify white blood cells. Cell counting was performed using a microscope. A total of 200 random cells was counted from each slide and included macrophages, lymphocytes, and neutrophils. Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: numbers remained persistently elevated through days 5 and 7. In addition, macrophages in BALF of the HAdV-7 group were significantly higher than the HAdV-3 group after 5 and 7 days of Note: Data are shown as medians or number Abbreviations: WBC white blood cell, CRP C-reactive protein \" a \": a significant difference between two groups infection , while the lymphocytes exhibited significant difference only on day 5 . Neutrophils in BALF of the HAdV-7 group was not significantly different compared with that of the HAdV-3 group at all time points . Together, these results showed that HAdV-7 infection induced", "Title: Age groups and spread of influenza: implications for vaccination strategy\nPassage: In the spring of 2009, the novel H1N1 influenza virus first emerged in Mexico and later spread widely throughout the world within just a few months. The World Health Organization announced on June 11 the start of 2009 influenza pandemic , and further issued an advisory on August 28 for countries in the northern hemisphere to prepare for a second wave of pandemic spread in the coming fall/winter . As of November 8, more than 206 countries and overseas territories or communities worldwide have reported laboratory confirmed cases of the pandemic pH1N1 virus, including over 6250 deaths . Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")", "Passage: a WHO pandemic alert phase 4 and 5 . The WHO raised their flu alert to level 5 on 29 th April , a mass media information campaign began in the UK on 5 th May 2009. We collected data from 30th April 2009 until 6th May 2009 . By 6 th May there had been 27 confirmed cases in Europe, but none in Asia. Title: Influenza A H1N1 2009 (Swine Flu) and Pregnancy", "Passage: Although the outbreak of influenza A H1N1 2009 appeared first in Mexico in April 2009, this was followed by a growing number of cases reported across the globe. The outbreak of the novel A H1N1 virus was declared a global pandemic by the World Health Organisation from 11 June 2009 until 10 August 2010. These pandemics happen when a new influenza virus, to which the population has little or no immunity emerges and starts to spread. Unlike seasonal influenza, high rates of disease due to a pandemic virus may occur throughout the year. Swine flu is a novel strain of Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: The name Spanish flu comes from the first news reports of influenza-like-illness in Madrid in the late spring of 1918. However, this pandemic gained its nickname because the first mentions of the virus were published in Spain, where the press faced no censorship during World War I, owing to the country's neutrality . Many people fell ill with respiratory symptoms in May 1918, including King Alfonso XIII, which was well documented in the press . Because respiratory disease outbreaks occurred in neighboring France as early as April 1918, it is likely that the virus was introduced into Spain via Spanish", "Title: The Trojan Chicken Study, Minnesota\nPassage: Some of our study findings were unanticipated. We expected contamination proportions to vary by age, gender, and role because we expected these factors to affect the amount of contact with birds and handwashing behavior. However the rates did not vary by these variables. This finding could be due to the study's limited power to detect such differences. If the differences between those exposed and those unexposed were statistically significant , they might be consistent with studies that suggest that animal handlers practice better hygiene compared to nonhandlers in the same environment. Alternatively, animal handlers may engage in other behavior that Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: A classic human study found that, in donors lacking neutralizing antibodies, pre-existing cytotoxic T-cell levels against influenza correlated with reduced virus shedding but not reduced symptoms after influenza virus challenge . Epidemiological studies of the 1957 pandemic, an H1N1 to H2N2 shift, suggested cross-protection, but these studies were too small for statistical significance or lacked laboratory confirmation of self-reported symptoms . A human challenge study found a correlation of CD4 memory with reduced illness duration, viral shedding, and symptom severity . Title: Comparing the outcomes of different postgraduate year training programs in Taiwan", "Passage: This study revealed no significant differences in medical knowledge and clinical performance among the four groups of trainees regardless of program, and showed that the learning results persisted long after the training ended if the programs were well-designed. The weaknesses of the study consisted of the limited number of stations that the trainees participated in during the clinical performance evaluation and possibly the high-quality MCQ items; however, the results still provide valuable information that can be used to improve the design of the training program such as arranging more core competencies in the 1-year program. Title: Chinese journals: a guide for epidemiologists\nPassage: results. However, subsequent studies found little evidence supporting this assertion. Pham et al. found that language bias led to an under-estimation of the protective effect of intervention in RCTs in complementary and alternative medicine systematic reviews but not in that of conventional medicine .", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Insights into the Evolution and Emergence of a Novel Infectious Disease\nPassage: Our work raises important questions for future research: where should surveillance be focused to detect an emergence as early as possible, especially if resources are limited? Given emergence of a novel infection in a rural setting, how much time can we buy through limiting travel to and from major urban centres? These and other questions will undoubtedly benefit from more systematic studies of emergence in the context of population distributions. Nonetheless, theoretical models such as those presented here can offer useful, fundamental insights to guide such studies. Title: Investments in respiratory infectious disease research 1997\u20132010: a systematic analysis of UK funding", "Passage: could be utilised. 33 It should also be noted that considerations other than incidence should ultimately influence the allocation of resources. Such considerations may include the prevalence and predicted impact of the disease, how treatable the disease is , cofactors and comorbities , consideration of how other types of research may impact and inform the issues of controlling spread of respiratory infectious disease and anticipation of future new tools, technologies or research methods. There must also be a supply line of individuals who are sufficiently skilled and motivated to carry out the research. Title: A bibliometric analysis of IL-35 research from 2009 to 2018\nPassage: further analysis. Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Answers to these questions are especially pertinent as basis for decisions on school closure as a social distancing intervention, which can be hugely disruptive not only for students but also because of its knock-on effect for child care and parental duties. Very few children have been confirmed 2019-nCoV cases so far but that does not necessarily mean that they are less susceptible or that they could not be latent carriers. Serosurveys in affected locations could inform this, in addition to truly assessing the clinical severity spectrum.", "Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies\nPassage: system. Recent evidence from genetic characterisation of human patients suggests that haploinsufficiency of KATNAL1 is linked with a number of symptoms including intellectual disability and craniofacial dysmorphologies. 8, 9 It is also notable that a very rare KATNAL1 mutation has been associated with schizophrenia 10 and that Peters syndrome and autism have both been associated with the chromosomal region containing the KATNAL1 locus. 11, 12 Although such association studies strongly suggest that KATNAL1 plays a fundamental role in the central nervous system , additional studies using cellular or animals models are required to understand how the gene may be causative Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: In summary the data presented here clearly demonstrate that KATNAL1 plays an important role in a variety of neuronal processes including neuronal migration, neuronal morphology and ependymal ciliary function. The downstream effect of these defects leads in turn to a number of behavioural changes including in learning and memory, reaction to anxiogenic situations and circadian rhythms. These data therefore highlight how perturbations in KATNAL1 may play a role in neuronal dysfunction and demonstrates that the enzyme is a novel candidate in the study of behavioural and neurodevelopmental disorders. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: In summary the data presented here clearly demonstrate that KATNAL1 plays an important role in a variety of neuronal processes including neuronal migration, neuronal morphology and ependymal ciliary function. The downstream effect of these defects leads in turn to a number of behavioural changes including in learning and memory, reaction to anxiogenic situations and circadian rhythms. These data therefore highlight how perturbations in KATNAL1 may play a role in neuronal dysfunction and demonstrates that the enzyme is a novel candidate in the study of behavioural and neurodevelopmental disorders. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: Recent evidence from genetic characterisation of human patients suggests that haploinsufficiency of KATNAL1 is linked with a number of symptoms including intellectual disability and craniofacial dysmorphologies. 8, 9 It is also notable that a very rare KATNAL1 mutation has been associated with schizophrenia 10 and that Peters syndrome and autism have both been associated with the chromosomal region containing the KATNAL1 locus. 11, 12 Although such association studies strongly suggest that KATNAL1 plays a fundamental role in the central nervous system , additional studies using cellular or animals models are required to understand how the gene may be causative for", "Title: Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis\nPassage: More positively, in one study, self-efficacy was highlighted as being important in helping reduce stress. Operatives who believed they were capable of coping, felt better able to deal with stressors, and experienced greater wellbeing . Title: Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis", "Passage: Work-life balance, such as adequate time off and outside interests, was considered vital, as was support from family and friends . Fire and police operatives who reported less social support experienced greater psychological distress following exposure to a hurricane , whilst having adequate social support was associated with reduced stress levels and better psychological health across all services . Not all operatives, however, reported gaining benefits from social support. Some reported feeling that friends and family lacked understanding, and so operatives sometimes chose not to discuss their job with them . Ambulance operatives reported that job stress and long working Title: Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis", "Passage: Physical layout and constricted or inadequate workspaces added to this sense of low control and increased stress . Ambulance operatives reported feeling out of control over their workload and current activity within their area of responsibility after returning from rest breaks; this fear of losing control meant they often chose not to take their allocated break time, even though such breaks were allowed during the working day . Title: Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis", "Passage: Some EDC operatives reported using strategies to mitigate some of the negative effects of workplace stressors; strategies included the use of emotion regulation and engaging in peer support. Some of the evidence from this review, however, suggests the EDC work environment does not always provide opportunities for sufficient peer support. Existing research from other emergency medical settings suggests that the peer support element of team working can be beneficial for managing stress and preventing burnout . Future interventions may therefore need to focus on increasing opportunities for peer support, to build resilience amongst EDC operatives.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: of active research for several reasons: in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins ; antibodies against a single epitope may be of limited utility, especially for highly variable pathogens ; and for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of active research for several reasons: in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins ; antibodies against a single epitope may be of limited utility, especially for highly variable pathogens ; and for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Despite this, the filamentous phage remains highly useful as a carrier for peptides with relatively simple secondary structures, which may be stablilized via anchoring to the coat proteins . This may be especially true of peptides with poor inherent immunogenicity, which may be increased by high-valency display and phage-associated adjuvanticity . Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: Despite this, the filamentous phage remains highly useful as a carrier for peptides with relatively simple secondary structures, which may be stablilized via anchoring to the coat proteins . This may be especially true of peptides with poor inherent immunogenicity, which may be increased by high-valency display and phage-associated adjuvanticity .", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: Rapid diagnostics plays an important role in disease and outbreak management. The fast and accurate diagnosis of a specific viral infection enables prompt and accurate public health surveillance, prevention and control measures. Local transmission and clusters can be prevented or delayed by isolation of laboratory-confirmed cases and their close contacts quarantined and monitored at home. Rapid diagnostic also facilitates other specific public health interventions such as closure of high-risk facilities and areas associated with the confirmed cases for prompt infection control and environmental decontamination . Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: MJA 210 \u25aa 15 April 2019 PCR was used, in contrast, our findings suggest that these decisions were made before the test results were available. The possible benefits of not admitting patients to hospital, beyond those for individual patient management, include better infection control and outbreak prevention, as well as reduced demands on hospital resources. 13, 14 The impact of rapid PCR testing on outbreak prevention and infection control measures should be evaluated. Rapid influenza virus testing may also have practical implications for hospital bed management. 10, 15 ED LOS was similar in our study before and after the introduction Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: Other studies have also reported that hospital admission numbers were significantly lower when rapid influenza virus testing was used in EDs. An analysis of outcomes for more than 300 adults at a tertiary care centre in New York found that early diagnosis of respiratory infections was associated with significantly fewer hospitalisations of influenza-positive patients. 7 In a small Irish study , the hospital admission rate for obstetric patients declined from 88% to 45% after on-site rapid influenza PCR testing was introduced. 10 The differences in clinical setting and patient group may explain the smaller decline in our study . Non-PCR-based Title: The impact of rapid molecular diagnostic testing for respiratory viruses on outcomes for emergency department patients", "Passage: Rapid, easy-to-use PCR-based respiratory virus diagnostic tests have been introduced in recent years; 6,7 the GeneXpert system , for instance, was introduced in New South Wales in July 2017. Rapid PCR tests were expected to facilitate timely and appropriate initiation of treatment, improve outbreak prevention and infection control measures, and expedite the assessment of patients in EDs.", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: Text: Japanese encephalitis virus, tick-borne encephalitis virus, eastern equine encephalitis virus , sindbis virus, and dengue virus are arboviruses and cause symptoms of encephalitis, with a wide range of severity and fatality rates . Establishment of an accurate and easy method for detection of these viruses is essential for the prevention and treatment of associated infectious diseases. Currently, ELISA and IFA are the methods which are clinically-available for the detection of encephalitis viral antigens, but they could only detect one pathogen in one assay . Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: There are a variety of different methods available for identifying multiple antigens in one sample simultaneously, such as two-dimensional gel electrophoresis , protein chip, mass spectrometry, and suspension array technology . However, the application of these techniques on pathogen detection is still in an early phase, perhaps due to the complicated use and high cost. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Abstract: Japanese encephalitis virus, tick-borne encephalitis virus, and eastern equine encephalitis virus can cause symptoms of encephalitis. Establishment of accurate and easy methods by which to detect these viruses is essential for the prevention and treatment of associated infectious diseases. Currently, there are still no multiple antigen detection methods available clinically. An ELISA-array, which detects multiple antigens, is easy to handle, and inexpensive, has enormous potential in pathogen detection. An ELISA-array method for the simultaneous detection of five encephalitis viruses was developed in this study. Seven monoclonal antibodies against five encephalitis-associated viruses were prepared and used for development of the Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Following a double antibody sandwich format, printed plates were incubated sequentially with inactivated viral cultures, biotin-labeled detecting antibody, HPR-labeled avidin, and substrate, followed by signal evaluation.", "Title: New Isoxazolidine-Conjugates of Quinazolinones\u2014Synthesis, Antiviral and Cytostatic Activity\nPassage: Several isoxazolidines trans-11/cis-11 were able to weakly inhibit the replication of TK + and TK \u2212 VZV strains with EC50 values in the range of 6.84-100 \u03bcM . Among them, phosphonates Ganciclovir, cidofovir, acyclovir, brivudin, zalcitabine, zanamivir, alovudine, amantadine, rimantadine, ribavirin, dextran sulfate , mycophenolic acid, Hippeastrum hybrid agglutinin and Urtica dioica agglutinin were used as the reference compounds. Title: New Isoxazolidine-Conjugates of Quinazolinones\u2014Synthesis, Antiviral and Cytostatic Activity", "Passage: To the solution of 2-vinyl-3H-quinazolin-4-one in acetonitrile potassium carbonate was added. After 15 min the respective benzyl bromide was added and the reaction mixture was stirred under reflux for 4 h. A solvent was removed and the residue was extracted with water . An organic layer was dried , concentrated and the crude product was purified on a silica gel column with a methylene chloride: hexane mixture followed by crystallisation to give pure quinazolinones 13b-e and 13g-i. 133.57, 128.60, 128.28, 128.25, 127.67, 126.60, 123.81, 123.61, 115.59, 68.32 . Anal. Calcd. for C 17 To the solution of 2-vinyl-3H-quinazolin-4-one in acetonitrile Title: Identification of Diaryl-Quinoline Compounds as Entry Inhibitors of Ebola Virus", "Passage: A549 cells were incubated with HIV-1/EBOV pseudovirions for 1 h at 4 \u2022 C, and the supernatant was removed from the wells and the cells were washed twice with PBS buffer. Fresh DMEM was added into the cells, and cells were then incubated at 37 \u2022 C in CO 2 incubator. At different time points, compounds were added with the final concentration of 10 \u00b5M. The experiment was performed in triplicate wells using benztropine as a control. Virus infection was quantified by luciferase signals 48 h after infection. For each time point, the data were normalized by the values from Title: New Isoxazolidine-Conjugates of Quinazolinones\u2014Synthesis, Antiviral and Cytostatic Activity", "Passage: 2-Vinyl-3H-quinazolin-4-ones 13 modified at N3 with substituted benzyl groups were synthesized from commercially available 2-aminobenzamide by acylation with 3-chloropropionyl chloride followed by cyclization and dehydrohalogenation to prepare 2-vinyl-3Hquinazolin-4-one as a key intermediate and a subsequent reaction with substituted benzyl bromides 13b-i . Moreover, compounds 13j and 13k were also obtained with intention to determine the influence of the benzyl substituent on biological activity of the designed isoxazolidines trans-11/cis-11. In the 1 H-NMR spectra of compounds 13a-k characteristic signals for vinyl protons were observed in the 6.94-5.59 ppm . Scheme 1. Retrosynthesis of phosphonates trans-11/cis-11.", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: The 2005-2006 epidemic of CHIKV in La Reunion islands in the Indian Ocean, spurred the discovery of a new vector species, Ae. albopictus . Wrecking over one-third of the island's population, this epidemic peaked its devastation between January and February 2006, when over 46,000 cases came into light every week, including 284 deaths . Ae. albopictus is common in urban areas of the United States and is already flourishing in 36 states, raising grave concerns to the immunologically naive populace of the United States . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: Within a year, the E1-A226V mutation was present in La Reunion Island, and Ae. albopictus apparently vectored the large epidemic infecting 34% of La Reunion Island's population . All of the CHIKV strains isolated from Mayotte carried the E1-A226V mutation, and the mutation was also found in Madagascar in 2007 . The E1-A226V mutation was not present at the beginning of the Indian Ocean Islands outbreak . However, more than 90% of later viral strains found there had incorporated the mutation , indicating a genotype switch during the winter season . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: CHIKV undertakes a complex replication cycle upon host infection , which makes its genome susceptible to mutations . For instance, Ae. aegypti, responsible for epidemics in Kenya, Comoros, and Seychelles, carried CHIKV with an alanine in the 226 position of the E1 gene . However, when the virus struck La Reunion Islands, a decline in population of Ae. aegypti, due to massive dichlorodiphenyltrichloroethane usage and dearth of Ae. albopictus species' www.plosntds.org population, resulted in an ecological pressure, favoring replacement of alanine at position 226 with valine . This mutation allowed CHIKV's secondary vector species, Ae. albopictus, to supplement Ae. aegypti Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: infection or severe disease, especially in the elderly. Interestingly, evidence is seen for a decline in antibody titers, which occurred soon after the passage of the epidemic wave. In paired sera, this decline was significant enough to bring, within a few weeks, almost 27% of sera that tested positive in the immediate post epidemic phase to levels under the cut-off value in the second serum sample. This decay accounts for the observation that older adults in the study cohort were apparently almost completely spared by the epidemic if one only considers cumulative incidence rates derived from IHA titration on samples", "Title: Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1\nPassage: spillover . In humans, VEEV causes a febrile illness typified by fever, malaise, and vomiting. In some cases, infection progresses to the central nervous system and neurological symptoms, such as confusion, ataxia, and seizures, manifest. The mortality rate among cases with neurological symptoms can be as high as 35% in children and 10% in adults, with long-term neurological deficits often being seen in survivors . In 1995, an outbreak of VEEV in Colombia and Venezuela resulted in over 100,000 human cases . In addition to natural outbreaks, VEEV is also a concern from a bioterrorism perspective, as it can be Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas", "Passage: hundreds-of-thousands of cases over a period of months to a few years. Prior to the 1980s, VEE epizootics involving high case-fatality rates were frequently recorded. Because horses have been an important component of the local agricultural economies within many Latin American regions, VEE has often had a sizeable economic impact as well as a direct effect on public and veterinary health . Recent outbreaks during the 1990s in Venezuela, Colombia and Mexico have demonstrated the potential for VEEV to re-emerge periodically from enzootic progenitors . The emergence of VEEV into an epidemic/ epizootic form has been associated with specific mutations Title: Treatment of Neuroterrorism", "Passage: Venezuelan equine encephalitis virus is an alphavirus that is most commonly found in Central and South America. It is transmitted to humans by mosquitoes. In case of a bioterrorist attack, the distribution would be made through aerosols . The virus usually leads to an initial severe febrile illness in nearly everyone exposed at 1 to 6 days after exposure. Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas", "Passage: climate change, which also increases the potential for other VEEV subtypes to spread northwards and establish enzootic transmission cycles. Although many VEE complex viruses have not been implicated in human disease, those that are associated with human disease can cause acute, often severe febrile illness that may progress to encephalitis, causing severe human morbidity and mortality . Patients who survive encephalitis are often left with permanent neurologic sequelae, and the cost for treatment and long-term care related to a single case can be several million dollars . In addition to VEEV , which cases the majority of the encephalitis cases", "Title: First Complete Genome Sequence of a French Bovine coronavirus Strain\nPassage: M, and N genes of the obtained BCoV were submitted to a Blastn analysis. According to these analyses, the orf1ab gene is closely related to the Dromedary camel coronavirus HKU23-23-362F strain from the United Arab Emirates , with a nucleotide identity of 99.19%. Conversely, the NS2, HE, S, ns5, and M genes are closely related to the BCoV Bubalus/Italy/179/07-11 strain , with nucleotide identities of 99.88%, 99.45%, 99.02%, 98.79%, and 99.28%, respectively. The E gene is closely related to the Chinese Bovine coronavirus strain BCV-AKS-01 , with a nucleotide identity of 100%. Finally, the highest Blastn score for the N Title: First Complete Genome Sequence of a French Bovine coronavirus Strain", "Passage: Text: B ovine coronavirus belongs to the Nidovirales order, the Coronaviridae family, the Coronavirinae subfamily, and the Betacoronavirus . Its genome is a single-stranded, linear, and nonsegmented RNA of around 31 kb. BCoV is responsible for respiratory and enteric diseases in cattle, particularly during winter . To date, the 19 complete BCoV genome sequences available in GenBank databases originated from the United States or Asia. Here, we report the first complete genome sequence of a BCoV detected in France. Title: First Complete Genome Sequence of a French Bovine coronavirus Strain", "Passage: N genes of American and Asian BCoVs group together in a cluster tentatively named C 1 . The nsp12 and N coding regions of BCoVs from France and DcCoVs from the United Arab Emirates clustered together in C 2 . The DcCoV S gene individualized from both HCoV-OC43 and BCoV S genes. Potential recombination events could be at the origin of DcCoV. Title: First Complete Genome Sequence of a French Bovine coronavirus Strain\nPassage: gene was found with the American enteric BCoV-ENT , associated with a nucleotide identity of 100%.", "Title: The origins of the great pandemic\nPassage: A second location, from which the influenza outbreak may first have been reported, is to be found in northern France. Lt J.A.B. Hammond and two colleagues encountered an outbreak of 'purulent bronchitis' in late 1916 and early 1917 at a hospital centre forming part of the British army encampment at Etaples. An initial paper was published by this group in The Lancet in July 1917 . This publication precipitated a rapid follow-up article, also in The Lancet, from an independent military group reporting similar observations at Aldershot, in the south of England . Looking back 2 years later, this second Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology", "Passage: between countries. One of the first case definitions used for national disease reporting was the case definition for AIDS published by the Centers for Disease Control and Prevention in 1982 . In 1985 Sacks published a survey among all 50 US states, Puerto Rico, and Washington, DC, that revealed important variations in the case definitions between the different states, and concluded the necessity to unify case definitions if surveillance data between states are to be compared . In 1990 the CDC in collaboration with the Council of State and Territorial Epidemiologists published an edition of case definitions for public health Title: The origins of the great pandemic", "Passage: Kansas cases no doubt make for a compelling story, but one that has perhaps left a stronger-than-deserved impression that they were the very first cases. Moreover, the noteworthy influenza outbreak at Camp Funston, Kansas, in March 2018, was mild, with many cases but few deaths. This was after New York City already had evidence of very high influenza mortality and increased mortality in young adults . The virus causing those cases in New York City in February presumably predated the March outbreak at Camp Funston. So what happened on this army base in Kansas was not the first large outbreak Title: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America", "Passage: The first laboratory confirmed case in Victoria was notified on 20 May. Figure 1 shows notified cases by date of onset and location of acquisition until the commencement of the Modified Sustain phase; pandemic phase changes and case identification milestones are also indicated. Only 5% of the first 100 cases in Victoria were imported, and only eight of the 977 cases diagnosed prior to the introduction of the Modified Sustain phase reported a travel history. The first five diagnosed cases reported travel to the Americas: three brothers from one family returned from the US, a visitor from Mexico and another", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Childhood pneumonia and clinically severe disease result from a complex interaction of host and environmental risk factors . Because of the effectiveness of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination for prevention of radiologic and clinical pneumonia, incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The single strongest risk factor for pneumonia is HIV infection, which is especially prevalent in children in sub-Saharan Africa. HIV-infected children have 6 times increased odds of developing severe pneumonia or of death compared to HIV-uninfected children . Since the effective prevention of mother-to-child transmission of HIV, there is a growing population of HIV-exposed children who are uninfected; their excess risk of pneumonia, compared to HIV unexposed children, has been described as 1.3-to 3.4-fold higher . Title: Risk factors for severe acute lower respiratory infections in children \u2013 a systematic review and meta-analysis", "Passage: Conclusion This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia. Title: Risk factors for severe acute lower respiratory infections in children \u2013 a systematic review and meta-analysis", "Passage: We systematically reviewed all literature published from January 1, 1990 through March 31, 2012 to identify studies with data on risk factors for pediatric pneumonia. We searched a variety of databases-Medline , Embase, CINAHL and Global Health Library using combinations of key search terms: pneumonia, low birth weight, undernutrition, breast feeding, crowding, smoking, indoor air pollution, immunization, HIV etc. . Hand searching of online journals was also performed by examining the reference lists for relevant articles. We did not apply any language or publication restrictions. Relevant full-text articles in foreign language were translated to English using Google translator.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: This section explains the proposed FPASSA-ANFIS method. It is a time series method for forecasting the confirmed cases of the COVID-19, as given in Figure 2 . The FPASSA-ANFIS utilizes the improved FPA to train the ANFIS model by optimizing its parameters. The FPASSA-ANFIS contains five layers as the classic ANFIS model. Layer 1 contains the input variables . Whereas Layer 5 produces the forecasted values. In the learning phase, the FPASSA is used to select the best weights between Layer 4 and Layer 5. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: algorithm . In general, SSA is employed to improve FPA to avoid its drawbacks . The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error , Root Mean Squared Relative Error , Root Mean Squared Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: The parameters of the ANFIS model are prepared by the FPASSA algorithm. In the training phase, the calculation error ) between the real data and the predicted data is used to evaluate the parameters' quality. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: This paper aims to assess the ability of the FPASSA to forecast the COVID-19 by comparing its performance with other methods, namely the ANFIS and the trained ANFIS models using PSO, GA, ABC, FPA, and FPASSA. The parameters' setting for these models is listed in Table 2 .", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: pressure/ fraction of inspired oxygen \u2264100 mmHg with positive end-expiratory pressure \u22655 cmH 2 O; and a chest radiograph with three or four quadrants with opacities. Patients with HAdV-55 infection and severe ARDS who failed conventional NPPV and invasive mechanical ventilation were included in the analysis. This study was approved by the Institutional Review Board of Beijing Chao-Yang Hospital . Data were analyzed anonymously. Each patient gave written informed consent for their data to be used for research and publication. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: pressure/ fraction of inspired oxygen \u2264100 mmHg with positive end-expiratory pressure \u22655 cmH 2 O; and a chest radiograph with three or four quadrants with opacities. Patients with HAdV-55 infection and severe ARDS who failed conventional NPPV and invasive mechanical ventilation were included in the analysis. This study was approved by the Institutional Review Board of Beijing Chao-Yang Hospital . Data were analyzed anonymously. Each patient gave written informed consent for their data to be used for research and publication. Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: In the chest radiographs , alveolar infiltration, consolidation and pleural effusion were more frequently observed with the HAdV-7 patients compared to HAdV-3 patients but they did not differ significantly. Increased lung texture and interstitial inflammation showed a similar proportion. Two patients infected with type 3, and four patients infected with type 7, had atelectasis. Notably, two patients infected with adenovirus type 7 had complications with pneumothorax. Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Patients' specimens, including sputum, whole blood and serum samples, were collected upon admission and during hospitalization. Microbiological tests were performed at the Department of Infectious Disease and Clinical Microbiology in our center, and the detection methods used were described in our previous report . Common viruses causing respiratory illness were screened using a kit with 15 different viral assays. Serum samples were used for Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila antibodies. All patients had their HAdV-55 infection confirmed by RT-PCR assay. Partial sequences of the hexon gene were analyzed to type the phylogeny of HAdV-55 strains. The adenoviral load", "Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")\nPassage: Five groups were seen as particularly at risk by more than half of our respondents: those with weakened immunity, pig farmers, the elderly, the homeless and prostitutes/ highly sexually active. Malaysians were more likely to see pig farmers, general farmers, homosexuals and prostitutes as at greater risk = 68.03, 11.44, 31.82, and 12.10, p < .001 for each), Europeans were more likely to see the elderly and those with weakened immunity at risk = 8.27, 3.49, p < .05). Whilst around half of our respondents reported they were at least 'somewhat concerned' about being a victim of the pandemic, this Title: Examining the knowledge, attitudes and practices of domestic and international university students towards seasonal and pandemic influenza", "Passage: Young children and the elderly were nominated as being the most vulnerable groups during a pandemic outbreak due to their 'sub-optimal immune systems'. Participants believed that children were less conscious about hygiene and were therefore more likely to be exposed to other infected children or contaminated objects in a school environment. On the other hand, teenagers and young adults , the 'physically and socially healthy' and the 'well educated' , were considered to be at lowest risk of contracting pandemic influenza. Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")", "Passage: An unrealistically optimistic belief that others are at greater risk than ourselves can reduce our willingness to enact healthy behaviours . During pandemics, particular 'out-groups' may be vulnerable to discrimination . Although respondents correctly identified groups such as the immunocompromised as at greater risk , half our respondents saw the sexually active as at greater risk, almost a third of Malaysians suggested homosexuals were at more risk of infection. This may reflect a popular belief in Malaysia that homosexuals are likely to be already immunocompromised through infection with HIV/AIDS. The homeless were also perceived as at greater risk in both Title: Ad Hoc Influenza Vaccination During Years of Significant Antigenic Drift in a Tropical City With 2 Seasonal Peaks: A Cross-Sectional Survey Among Health Care Practitioners", "Passage: Turning to the perceived vaccine recipient group which should be given priority if the government has limited doses, the top priority selected was the elderly aged !65 years with chronic medical conditions , followed by the elderly living in residential care homes , long-stay residents of institutions for the disabled , the elderly aged !65 years , and healthcare workers in residential care homes , whereas pregnant women were regarded as lowest priority . Most respondents strongly agreed or agreed that doctors , nurses , and allied health professionals should be given a top priority for receiving the new vaccine.", "Title: What Effect Did the Global Financial Crisis Have Upon Youth Wellbeing? Evidence From Four Australian Cohorts\nPassage: States and the United Kingdom, let alone Greece, Italy, Ireland, and Spain, was considerable. Importantly, given our focus on the population as a whole, unmoderated by individual exposure, the effect sizes of above .10 standard deviation units, and often above .15, were concerning given effects of unemployment of .50 . This suggests that for particularly vulnerable groups, for example those who experienced the largest relative loss in status or income or became unemployed, the findings may have been considerably more dramatic. Title: What Effect Did the Global Financial Crisis Have Upon Youth Wellbeing? Evidence From Four Australian Cohorts\nPassage: were particularly at risk . Title: What Effect Did the Global Financial Crisis Have Upon Youth Wellbeing? Evidence From Four Australian Cohorts", "Passage: The close-up graphs provide strong evidence for the negative impact of the GFC with most of the relevant contrasts displaying overlapping confidence intervals in the years prior to the GFC before diverging. It was on this basis that we explored the hypotheses using PSM and DID models. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: Also, there were numerous sub-topics with a great number of reviews available. Table 6 identifies 71 subtopics with more than 25 reviews available. Such subtopics included, but were not limited to, alcohol abuse/ use, smoking cessation, women's health, cancer, cardiovascular disease, lifestyle behaviours, disease transmission, depression, diet, healthy weight, exercise, and HIV. As well, most of these sub-topics were within the registered users and visitors' topic areas of interest, with the exception of dental health, senior health, sexual health, and sexually transmitted infections. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: topic areas. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: The top 10 topic areas of interest of registered users and the top 10 topic areas of interest of visitors of http:// www.health-evidence.ca, as well as the availability of review evidence by methodological quality, are identified in Table 1 . The top areas of interest and the total number of reviews available included: addiction/substance use , adolescent health , adult health , child health , chronic diseases , communicable disease/infection , healthy communities , injury prevention/safety , mental health , nutrition , parenting , physical activity , reproductive health , and social determinants of health . Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: Topic areas with a moderate number of reviews included: infant health , senior health , sexual health , sexually transmitted infections , communicable disease/infection , reproductive health , parenting , and, injury prevention/safety . Four of these eight topic areas have expressed interest by visitors or registered users. For visitors, ranking at fifth, eighth and tenth place respectively, searches submitted in 2010 for parenting totalled 1, 813 pageviews, for injury prevention/safety 1, 360, and, for reproductive health 1, 273 pageviews. Ranking tenth place, 1, 422 registered users indicated interest in the topic communicable disease/infection.", "Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: Another contributing factor to the low pertussis incidence observed could be that surveillance was conducted during a period of low pertussis transmission. Pertussis is a cyclical disease, thought to peak every 2 to 4 years, and we may have captured the burden at a low circulation period . We observed over 70% of our B pertussis cases over a 1-year period. This increase from earlier observation periods could indicate a temporary rise in pertussis consistent with its cyclical pattern or a true increase in the baseline burden. Previous research on pertussis seasonality has in different places and time periods demonstrated Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: The average pertussis episode duration was 8 days . Mean age of onset of symptoms was 83 days . The most common symptoms were cough, difficulty breathing, and cough with vomit. None of the additional symptoms related to pertussis that were added in year 2 resulted in collection of nasal swabs based solely on these additional symptoms. Pertussis episodes were statistically significantly more likely to include difficulty breathing, cough with vomit, and whoop compared with other respiratory illness. Six infants had at least 1 pertussis vaccination before pertussis disease onset with a mean of 18 days from vaccination to illness Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: compared with 49 days for nonpertussis episodes . Five infants received their first pertussis vaccination postpertussis disease onset, whereas 6 infants received no pertussis vaccination in the first 180 days. Three fourths of pertussis episodes were coinfected with at least 1 virus, with RV and BoV the most common. Cases of pertussis were more likely to be infected with BoV than respiratory cases due to causes other than pertussis. The majority of cases occurred between February 2013 and January 2014 . Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: The average B parapertussis episode duration was 4 days . Mean age of onset of symptoms was 58 days with a range of 7-95 days. The most common symptoms were cough and wheeze. Rhinovirus and RSV were the only coinfections observed. All B parapertussis cases occurred between September 2011 and February 2012 .", "Title: Lost in Translation (LiT)\nPassage: HTS had its origin in natural product screening by 1986 by Pfizer and others. By the early 1990s, HTS, plus combinatorial chemistry, was being promoted as the solution to improve productivity in drug discovery. Companies invested heavily in highly automated facilities and in assembling large compound libraries. HTS methods were later adapted to measure some drug metabolism and safety targets. Title: High Throughput Screening for Small Molecule Enhancers of the Interferon Signaling Pathway to Drive Next-Generation Antiviral Drug Discovery", "Passage: The raw data from the HTS assay were subjected to statistical analysis using cellHTS2 , a software package designed for the analysis of HTS data as part of the Bioconductor project for statistical computing . Raw data were normalized using the plate median method . Next, a z-score transformation was applied to center and scale the data across the experiment. Replicates for a given compound at a given dose were then mean summarized. A zscore threshold of $2 was chosen to identify potential hits. Title: Docking, virtual high throughput screening and in silico fragment-based drug design", "Passage: High throughput screening is typically used at an early stage of the drug design process in order to test a large compound collection for potential activity against the chosen target . Unfortunately, HTS is time consuming and costly. For this reason, its computational corollary, the vHTS, has become an important tool to precede the large in vitro screening assays performed in pharmaceutical companies . vHTS aims at using computational tools to estimate a priori, from an entire database of existing compounds , those that are the most likely to have some affinity for the target. There are basically two approaches Title: Lost in Translation (LiT)", "Passage: Highly automated parallel syntheses that produced singlet molecules with known structures largely superseded this approach, but the aim remained to produce enormous libraries to feed the screens. HTS initially used ligand binding assays, although later cell-based assays were widely adopted. The problem was that the HTS 'hits' with the highest binding to the target were often relatively large lipophilic molecules. The chemists working on 'hit to lead' and 'lead optimization' were more likely to add groups than subtract them. The end result was often a highly lipohilic, high MW molecule with very low water solubility at the pH of the", "Title: Antibody Engineering for Pursuing a Healthier Future\nPassage: Phage libraries are useful for mapping antibody epitopes, and display millions of peptides/proteins with unique random sequences. Antibodies select peptides according to the affinity of paratopes from the libraries . Title: Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines", "Passage: Random Peptide Libraries is one common application of IAVs, where random oligopeptides are displayed on different clones of an inovirus particle. The vast diversity of an RPL depends on the size of the oligopeptide where the complexity of an RPL increases exponentially as the size of the oligopeptide increases. RPLs can subsequently be used in many applications including the identification of peptide ligands by receptors, the mapping of substrate sites for enzymes, and the creation of antibody peptide libraries. These applications are reviewed elsewhere . Inovirus display technology has also been used for epitope mapping and vaccine design purposes. RPLs Title: Screening of Random Peptide Library of Hemagglutinin from Pandemic 2009 A(H1N1) Influenza Virus Reveals Unexpected Antigenically Important Regions", "Passage: Inspired by advances in cell surface display technology and peptide fragment library construction , we devised a highthroughput scheme that utilizes yeast display and FACS that allows for direct screening of random viral peptide libraries against complex antisera instead of isolated antibodies . The peptide library is generated by random digestion of the gene encoding the target viral protein, followed by a PCR-based reassembly step that results in fragments with controllable lengths . These peptides are then expressed on the yeast cell surface by fusion to the yeast adhesion receptor AGA 2 protein, which has previously been used to display Title: Screening of Random Peptide Library of Hemagglutinin from Pandemic 2009 A(H1N1) Influenza Virus Reveals Unexpected Antigenically Important Regions", "Passage: of bacteriophage, bacteria and yeast , which in recent years have increasingly incorporated fluorescence-activated cell sorting . In these efforts, short defined or random peptides with a narrow length range ) are used to screen against monoclonal or polyclonal antibodies.", "Title: Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing\nPassage: We detected virus sequence at concentrations as low as ,2 in 10 6 reads. Virus sequence detected in a clinical sample at vanishingly low copy numbers may reflect several possible hostmicrobe scenarios. The sequence detected may be that of a pathogenic virus capable of causing illness at low copy number or through indirect effects, a ubiquitous non-disease causing microbe, a virus outside of its primary replication site, low-level contamination, an artifact of sample collection timing/processing, or remains of incomplete immune clearance. Additional evidence must be considered in each case to define the host-microbe relationship. Title: A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections", "Passage: of the individual features and their combinations , see Fig. 3A ). Figure S11. Box plots of clinical parameters and laboratory measurements in bacterial, viral, and non-infectious patients in the entire study cohort . Red line and circle correspond to group median and average respectively. T-test p-values between bacterial and viral groups and between infectious vs non-infectious are depicted. Title: Influenza virus-related critical illness: prevention, diagnosis, treatment\nPassage: not interpretable . Although viral culture can confirm the presence of infectious virus with very high sensitivity and specificity, it must be performed at public health laboratories and requires 3-10 days to yield results. Title: A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections", "Passage: the levels of multiple proteins into a bacterial likelihood score. Patients whose probability of bacterial infection was intermediate, between 0.35 and 0.55, were flagged. We use the term 'equivocal immune response' to describe these patients because their profile borders between bacterial and viral host-responses. Statistical analysis was performed using MATLAB .", "Title: Viral factors in influenza pandemic risk assessment\nPassage: Ultimately, it would be valuable to develop a simple screen to assess the ability of a viral polymerase to support replication and transmission in humans. This phenotype is influenced by at least 4 different viral genes and involves interactions with several different human host factors. If all the relevant host factors were enumerated, one could imagine quickly converting sequence information into an assay that tested for interactions that should support activity. Along these lines the recent description of a host factor, ANP32A that differs between flighted birds and mammals and explains the poor activity of avian polymerase in mammalian cells Title: Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host\u2019s Transcriptome: The Tobacco Etch Potyvirus\u2014Tobacco Case Study", "Passage: diversity of transcription factors including global , sequence-specific , GATA/NAC family members , bZIP G-box finding factors , and involved in homeotic gene expression . We also found genes related to genome integrity, , DNA replication and nucleosome assembly, alternative splicing , chromatin transition , DNA replication, and cell division . However, not all host factors recruited by the virus present alterations in their expression. According to our data, the translation initiation factor eIF4E, known to be exploited by TEV for its own translation , was found to be unperturbed while eIF3A and eIF4G expression is positively correlated with TEV Title: Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host\u2019s Transcriptome: The Tobacco Etch Potyvirus\u2014Tobacco Case Study", "Passage: GASA1 and VQ29, brassinosteroids , ethylene response factors , and members of abscisic acid perception pathway . Likewise, genes involved in methylation-mediated stress responses, such ADK2, FDM1 or the methionine adenosyltransferase MAT3 reduce their expression as virus replication is more efficient, thus resulting in less methylation and increased expression of genes that participate in apoptosis and posttranscriptional gene silencing . In this way, the overexpression of genes that modulate histone acetylation or chromatin organization, such as the histone acetyltransferase HAC1 and the chromatin remodeling factor R17 would regulate differentiation, apoptosis, transcriptional activation, or ethylene response just as viral fitness increases. Title: Ebola Virion Attachment and Entry into Human Macrophages Profoundly Effects Early Cellular Gene Expression", "Passage: rigorous pathway analyses to the datasets. Ebola virus was found to significantly regulate the expression of over 88 host genes. These changes occurred within the first hours of infection. Subsequent experiments demonstrated that virus replication was not necessary for activation. Indeed, noninfectious virus-like particles expressing the ebolavirus glycoprotein and matrix proteins were sufficient stimuli to induce activation.", "Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris\nPassage: secretion to display for full length IgGs, they suffer drawbacks of their own, including the need for modifying the protein sequence to allow surface binding in particular cases. Moreover, re-capture following secretion introduces the risk of \"crosstalk\" between clones that could lead to the loss of the required genotype-to-phenotype relationship that is critical for efficient lead-cell isolation. Without a strong genotype-to-phenotype relationship built into the display system the issue of \"cross talk\" among clones in the same culture must be addressed through tedious experimental modifications . Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: Surface display boasts the ability to link genotype to phenotype. In the classical antibody display paradigms, sorted clones are isolated and their genotypes are subcloned into new production hosts. This cloning step involves screening multiple clones to isolate ones with defined properties. The anchored Fc system side-steps the need for these additional steps by combining selection of antibody affinity and production host in a single experiment. Libraries can be generated and displayed in the cell line of choice, such as Glyco-engineered Pichia pastoris. Selected clones can be fermented directly in small or large scale vessels to generate material for in Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: We have presented the development of a novel dual-mode display and secretion technology in Glyco-engineered Pichia pastoris, and demonstrated the utility of this method in selecting mAb leads with variable affinities and high productivity. The combination of display and secretion in the same clone enables the continuity and fidelity of the antibody discovery process and could lead to shortened maturation cycle and desirable lead developability. Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: Flow cytometric analysis and cell sorting were performed on a FACSAria cell sorter with blue and red lasers equipped with FACSDiva software. The procedure was performed according to Lin et al. . Gating in a dot plot of FSC vs. SSC was routinely applied to exclude cell debris and to include a population of single cells with similar size for analysis and sorting. For each sort, the 1% of cells with the brightest signal were gated and 5000-10,000 total cells were collected. Flow cytometry data were analyzed with software FlowJo v 7.1.2 .", "Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland\nPassage: Because of polymorphism in this region, this region could be useful for epidemiological investigation . The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the viruses in Ireland may be distinguishable from those circulating in other countries. The positive samples were collected in November , March and April in this study. Higher case numbers are identified in the USA during the colder months , and our results were consistent with the circulation period in USA. It has been reported that outbreaks mainly occurred among adult riding, racing and show horses in USA . The Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: Both molecular and seroepidemiology studies suggest that ECoV may be more prevalent in the USA than in other countries . ECoV was detected in samples collected from equids in 48 states of the USA . In central Kentucky, approximately 30% of both healthy and diarrheic Thoroughbred foals were infected with ECoV . All of the qPCR positive foals with diarrhoea were co-infected with other pathogens such as rotavirus or Clostridium perfringens, suggesting that there was potential for ECoV to be over-diagnosed as a causative agent in complex diseases. In contrast in Japan, although an outbreak of diarrhoea occurred among ECoV-infected Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: five for Great Britain, France and the USA . Thus, an investigation of ECoV in Ireland is pertinent not only to increase awareness nationally of the epidemiology of the virus and promote discussion on its clinical importance, but also to inform the industry globally of the health status of Irish horses. Ireland exports horses all over the world. By illustration, in 2016 the country was the second biggest seller of bloodstock at public auctions second only to the USA . Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: Many questions remain with regard to the clinical significance of ECoV. The outbreak at a draft-horse racetrack in Japan in 2009 affected 132 of approximately 600 horses and resulted in non-starters and the implementation of movement restrictions . However, draft horses appear to have a higher infection rate than other breeds and an outbreak of similar severity has not been reported in Thoroughbred racehorses . The much higher incidence of ECoV positive Thoroughbred foals identified in Kentucky compared to similar populations internationally suggests an increased susceptibility to ECoV infection in that population. In the past, specific environmental factors were associated", "Title: A novel framework for inferring parameters of transmission from viral sequence data\nPassage: transmission. Title: Transmission Dynamics and Prospects for the Elimination of Canine Rabies\nPassage: regarding data availability. Title: Requirement of CRTC1 coactivator for hepatitis B virus transcription\nPassage: . Collectively, our results suggest that CRTC1 is required for HBV transcription and replication. Title: A novel framework for inferring parameters of transmission from viral sequence data\nPassage: making it through the bottleneck to found the next generation.", "Title: A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies\nPassage: greater than log 3.0 and, conversely, 3.5% displayed a titer below the cut-off value, i.e. log 1.25 . Thus, of 57 HCV-infected patients, only two did not test positive for neutralizing antibodies in this assay . Title: A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies", "Passage: titers of purified serum immunoglobulin samples from seventy-seven individuals were determined using a 50% focus reduction neutralization assay. Each titer was determined as the log value of the reciprocal antibody dilution that reduced the number of viral foci by 50%. IgG antibodies were first purified from each serum in order to avoid the facilitating effect of HDL on HCV entry. RESULTS: The assay's cut-off using an ELISA and RNA HCV-negative samples was found to be 1.25 log, corresponding to a dilution of 1:18. The assay was compared with a commercial HCV ELISA and exhibited specificity and sensitivity values of 100% Title: Development of in vitro and in vivo rabies virus neutralization assays based on a high-titer pseudovirus system", "Passage: RFFIT; most of these seven values were close to the cutoff value , indicating discordance was mainly associated with serum samples with very low levels of antibodies, i.e., near the borderline set for positive value. Title: Distribution of antibodies against influenza virus in pigs from farrow-to-finish farms in Minas Gerais state, Brazil\nPassage: low; 160-320, medium; and \u2265640, high. Values were expressed by mean log 2 antibody titers. Means log 2 antibody titers are equivalent to HI titers: 4\u00c132 = 20; 5\u00c132 = 40; 6\u00c132 = 80; 7\u00c132 = 160; 8\u00c132 = 320; and 9\u00c132 = 640. A herd was considered positive when at least one of the animals was seropositive.", "Title: The origins of the great pandemic\nPassage: Those who have chronicled the march of this pandemic have pointed to two distinct phases through which, during the year 1918, its incidence had moved. The first phase, which began in spring and lasted until August, was characterized by an acute onset and high fever. The illness was of short duration and fatalities were relatively few. Then followed, from the autumn onwards, a second and more destructive phase. It affected all ages and conditions, but as noted above its effects on young adults were particularly marked. Title: CDC Summary 21 MAR 2020,", "Passage: Different parts of the country are seeing different levels of COVID-19 activity. The United States nationally is in the initiation phase of the pandemic. States in which community spread is occurring are in the acceleration phase. The duration and severity of each pandemic phase can vary depending on the characteristics of the virus and the public health response. Title: Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus\nPassage: For example, when a 99% restriction of all transports was imposed, the peak was averagely deferred to the ninth month and the eleventh month respectively in absences and presences of the uses of antiviral and hospitalization. Title: The origins of the great pandemic\nPassage: the initiation of its most intense wave.", "Title: Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance\nPassage: them to the scientific community for further investigation. Title: Multifunctional biophotonic nanostructures inspired by longtail glasswing butterfly for medical devices", "Passage: Both sensors were retrieved after one month of implantation to quantify cell growth on surface and to assess biocompatibility. We used confocal fluorescence microscopy to determine the extent of tissue growth and cellular viability at the time of retrieval. DAPI was used to localize all constituent cells while Phalloidin, which selectively binds to actin, was used as an indicator of cellular processes and health 48 . Additionally, matrix metalloproteinases-2 was used as an indicator of inflammation for its role in various inflammatory and repair processes 49 . Fig. 5e and 5f show the top views of the z-stacked multi-channel immunofluorescence Title: Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton", "Passage: Confocal microscopy: Laser scanning microscopy Spinning disc confocal microscopy Eliminated out of focus light increases contrast Good multi-dimensional spatial and temporal resolution Phototoxicity and photobleaching, particularly for laser scanning confocal microscopy AdV-C2 , Poliovirus , Reovirus Photoactivated localization microscopy Superior spatial resolution Most powerful with fixed samples Limited availability of photoswitching labels for PALM and STORM Some fluorophores require special buffers that can affect cell viability Low time resolution limits usefulness for live cell imaging High demand on data post-processing Rotavirus VSV-like particles Influenza A virus Light sheet microscopy: Diffraction-limited light microscopy has a spatial resolution in the range of Title: Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy", "Passage: Imaging studies under experimental in vitro conditions revealed exciting details of the replication cycle of many different viruses. Virus entry through endocytosis and fusion, intracellular trafficking and nuclear import, and assembly and release of viral particles has been extensively studied in vitro using cancer cell lines and primary cells. Thereby, fluorescence microscopy played an important role as the visualization of viral and cellular proteins by fusion to fluorescent proteins or immunostaining allowed researchers to define subcellular structures that are critical for various steps of the viral life cycle. In particular, live cell imaging using confocal laser-scanning or spinning-disk microscopy provided", "Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: done by means several techniques . Title: Use and Evaluation of Molecular Diagnostics for Pneumonia Etiology Studies\nPassage: Respiratory diagnostics are further complicated by the absence of a perfect gold standard. Culture is difficult or insensitive for some pathogens and unavailable for others . Serologic tests are often not available and usually require paired serum specimens for accurate results. Statistical methods to adjust for such alloyed gold standards, such as discrepant analysis, have been frequently employed, but they can be susceptible to significant bias . Comparative evaluations of respiratory diagnostic assays must also take into account variations in which panel of pathogens is selected, which genetic sequences are targeted, what specimen sources are used , and even what Title: Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine", "Passage: Disease emergence and bioterrorism events, especially since 2001, have highlighted some of the short-comings of traditional surveillance, generally based on laboratory test results and direct reporting . Focus has shifted to earlier detection of pathogen introduction in human or animal populations, leading to the implementation of new techniques using data sources upstream to those typically used in traditional surveillance ; especially prediagnosis data that are already available and automatically collected , such as sales of over-the-counter medicine, absences from work or school, and patients' chief complaint upon visits to an emergency center . Title: Retrospective diagnosis of a famous historical figure: ontological, epistemic, and ethical considerations", "Passage: The last but not the least relevant point is that medical diagnosis has several methodological dimensions. One condition can be diagnosed from many different dimensions: by clinical signs and symptoms ; by laboratory tests ; by genetic tests ; by identifying etiology ; by pathological examination . These methodological dimensions are not synonymous labels for the same condition. For example, AIDS and HIV infection are not synonymous; a patient can have the latter without former. Which methodological dimension to be used depends on the clinical context. As already mentioned, the diagnosis of \"viral syndrome\" is sufficient without etiological or laboratory", "Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: new research by other researchers in Kenya and other countries on other health problems. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: A lay summary of the results will be shared with the participating schools and households, as well as and communities surrounding the schools. Manuscripts will be submitted to appropriate journals discussing the methods, statistical analysis and output, and applications of the data in mathematical modelling of respiratory disease transmission and control. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: it might be worth considering how the proposed proximity data might relate to existing diary-based studies. Title: A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan\nPassage: sample material.", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: As at 09:00 on 21 February 2020, 47 confirmed cases of COVID-19 were reported in the WHO European Region and one of these cases had died . Data on 38 of these cases are included in this analysis. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: 2 days to be hospitalised.", "Title: Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014\nPassage: Soap is more effective at removing pathogens than washing with water alone . According to a meta-analysis of more than 30 hand hygiene studies conducted between 1960 and 2007, handwashing contributed to reducing digestive and respiratory system diseases by 31% , 19% to 42%) and 21% , respectively. The most efficacious intervention was handwashing with soap, with no difference in efficacy between antimicrobial and nonantimicrobial soap . Title: Associations of hand-washing frequency with incidence of acute respiratory tract infection and influenza-like illness in adults: a population-based study in Sweden", "Passage: Our negative results may seem counterintuitive and in conflict with the existing literature. However, although many studies conclude that hand-washing should be recommended as a public health measure in the face of threatening upper respiratory tract virus epidemics, the scientific evidence remains unconvincing. To a large extent, the evidence is derived from studies among children , in whom the baseline hand hygiene is often imperfect and the interventions are typically enforced by dedicated adults, in non-blinded cluster-randomized trials with risks for Hawthorne effects and biased outcome assessment, or in hospital-based case-control studies with their known risk of bias. Moreover, despite Title: Associations of hand-washing frequency with incidence of acute respiratory tract infection and influenza-like illness in adults: a population-based study in Sweden", "Passage: Acute respiratory tract infections constitute a large part of the total disease burden among people in productive ages and cause significant costs for society . Hand-washing is typically recommended as a central non-pharmacological measure against ARI, but the evidence for its effectiveness is surprisingly sparse, weak and divergent . Cluster-randomized non-blinded intervention trials, sometimes combining hand hygiene with wearing of face masks, in households with newly infected index cases generally failed to statistically confirm protective effects on primary outcomes , but some found significant protection in subgroups that started intervention early . Public health intervention trials with clusterrandomization in more Title: Associations of hand-washing frequency with incidence of acute respiratory tract infection and influenza-like illness in adults: a population-based study in Sweden", "Passage: A recent Finnish cluster-randomized intervention study found a significant effect of hand-hygiene with soap and water on ARI occurrence, but when the influenza A 2009 pandemic struck, a concurrent nationwide campaign for improved hand hygiene seemingly annulled differences between the intervention arms . Since our study coincided with the influenza pandemic in Sweden we cannot exclude the possibility that temporary changes in hand hygiene habits may have attenuated possible protective effects of the reported habitual washing pattern. However, subanalyses in the influenza highseason and the post-peak season did not reveal any important differences. Interaction between hand-washing and contact behaviour was", "Title: Year in review 2012: Critical Care - respiratory infections\nPassage: score of greater than 0.5 had a sensitivity of 0.75 and a specifi city of 0.71 for determining the risk of MDR pathogens. But more importantly, among patients with a score of not more than 0.5 on entry, the prevalence of resistant bacteria was 8%, compared with 38% in those with a score of at least 3 . Th e fi ndings suggest a way to stratify patients with HCAP, so that not all would have required empiric broad-spectrum therapy. Title: Coinfection and Mortality in Pneumonia-Related Acute Respiratory Distress Syndrome Patients with Bronchoalveolar Lavage: A Prospective Observational Study", "Passage: Of the 142 pathogen-positive patients, 55 had bacterial, 88 had viral, and 81 had fungal pathogens . A total of 55 bacterial pathogens were identified in 42 patients: two pathogens were identified in eight patients, and three pathogens in two patients. Gram-negative bacteria were more common than gram-positive bacteria vs. n \u00bc 10 ). The most common gram-negative and gram-positive bacteria were P aeruginosa and methicillinresistant S aureus, respectively. A total of 88 viral pathogens were identified in 82 patients: two pathogens were identified in six patients. The most common virus was CMV, followed by influenza. A total of 81 Title: Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?", "Passage: During the study period, 618 patients were admitted to our adult ICUs. Overall, one or more TA samples were obtained from 105 patients, and a microbiologic diagnosis was made in 65 of them . Bacterial infection was diagnosed in 29 patients, and the frequencies of the pathogens isolated were as follows: Staphylococcus aureus, 37.9%; Enterobacteriaceae, 24.1%; Pseudomonas aeruginosa, 17.2%; Streptococcus pneumoniae, 13.7%; and Acinetobacter baumannii, 6.8%. A diagnosis of viral infection only was made in 25 patients: 23 with influenza virus, one with adenovirus, and one with herpes simplex virus. Aspergillus fumigatus was the only microorganism isolated in three patients. Title: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China", "Passage: Overall, 48\u00c10% of our cases were positive for respiratory virus infections, which resembled the latest study in the same city. 21 A similar incidence rate has been obtained in neighboring regions 13, 22 and other cities such as Rome 23 and Milan, 24 but it was different from other studies. In China, the overall positive rate reported varied from 27\u00c13 to 74\u00c18% depending on different areas and detection methods. 15, 16, The rate of respiratory viral infections varied worldwide, and many factors such as geographic distribu-tion, study design and detection protocols could lead to these variations. 1, 7, 8, 32", "Title: Activation of the Cellular Unfolded Protein Response by Recombinant Adeno-Associated Virus Vectors\nPassage: A massive influx of exogenous proteins such as in the case of viral infection is also known to trigger UPR, to maintain cellular homeostasis . Several viruses such as herpes simplex virus, cytomegalovirus and others are known to induce ER stress and UPR signalling pathways . While some of them such as influenza virus and rotavirus manipulate these UPR pathways to establish its productive infection many viruses such as Japanese encephalitis virus and Tula virus succumb to its activation due to cross activation of UPREs . NF-kB is a major transcription factor activated in response to UPR signalling that results Title: Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo", "Passage: Here we demonstrate that the ER stress response, in particular the ire-1 arm, is activated upon exposure of C. elegans and mammalian cells to PFTs. We demonstrate for the first time that the ire-1 -xbp-1 arm of the UPR is functionally important for defense against a pathogenic attack since loss of this pathway leads to animals hypersensitive to PFT, but not to other toxic insults. Furthermore, we demonstrate that activation of the ire-1-xbp-1 pathway by PFT requires p38 MAPK and its associated MAPK kinase and that the in vivo response of the UPR to a PFT can be separated from Title: Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo", "Passage: A link between the p38 and UPR pathways has been shown in previous studies, although not with the level of functional relevance demonstrated here. Various arms of the UPR have been shown as both upstream or downstream of the p38 pathway, depending on the circumstances . The p38 pathway itself is implicated extensively in innate immune protection of many organisms against pathogens and against PFTs in worms and mammals . Our data presented here for the first time functionally link the UPR to this major innate immune signal transduction pathway. Our findings on the activation and role of the UPR Title: Activation of the Cellular Unfolded Protein Response by Recombinant Adeno-Associated Virus Vectors", "Passage: The ultimate effect of UPR is a paradox where it can either have a cyto-protective effect by restoring cellular homeostasis or can lead to cell death via apoptosis. The activation of the PERK or the combined activation of PERK and IRE1a pathways can lead to enhanced ER protein folding capacity and clearance of misfolded ER proteins or provoke innate immune response against viral proteins. However, depending on the strength of UPR activation, the cells can no longer have the opportunity to restore cellular homeostasis and may eventually lead to apoptosis. It is intriguing though how an identical scAAV genome packaged", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: Text: Since mid-December 2019 and as of early February 2020, the 2019 novel coronavirus originating from Wuhan has infected over 25,000 laboratory-confirmed cases across 28 countries with about 500 deaths . More than 90% of the cases and deaths were in China . Based on the initial reported surge of cases in Wuhan, the majority were males with a median age of 55 years and linked to the Huanan Seafood Wholesale Market . Most of the reported cases had similar symptoms at the onset of illness such as fever, cough, and myalgia or fatigue. Most cases developed pneumonia and some Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: The 2019-nCoV infected cases have symptoms like fever, fatigue, dry cough, dyspnea etc., with or without nasal congestion, runny nose or other upper respiratory symptoms . Despite the atypical symptoms were reported , Nan-Shan Zhong, the academician of Chinese Academy of Engineering in an exclusive interview with Xinhua News Agency on 28 January 2020, pointed out that fever is still the typical symptom of 2019-nCoV infection. Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: Text: In December 2019, the 2019 novel coronavirus was discovered and identified in the viral pneumonia cases that occurred in Wuhan, Hubei Province, China; And then was named by the World Health Organization on 12 January 2020. In the following month, the 2019-nCoV quickly spreading inside and outside of Hubei Province and even other countries. What's more, the sharp increase of the case number caused widespread panic among the people. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia", "Title: Inference and forecast of H7N9 influenza in China, 2013 to 2015\nPassage: when infection is suspected, culled, as required by the Chinese government . Title: Inference and forecast of H7N9 influenza in China, 2013 to 2015\nPassage: early stages of the outbreaks. This probably reduced chicken-to-human exposure and chicken-tochicken mixing and consequently may have attenuated the severity of the outbreak. On the other hand, for southern provinces such as Guangdong , co-circulation of a diverse array of avian influenza subtypes as well as multiple strains of H7N9 and H9N2 influenza viruses has been documented. This abundance of viruses creates an environment primed for influenza reassortment, resulting in diversified and more adaptive genotypes and a higher risk of infections in both poultry and humans and may therefore keep susceptibility high and stable across seasons. Title: Inference and forecast of H7N9 influenza in China, 2013 to 2015", "Passage: at the beginning of the outbreak at a national scale . Title: A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014\nPassage: . The genotype analysis of the H7N9 virus was classified by the criteria previously described 3 .", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: On the other end of the spectrum, viruses that induce strong type 1 inflammation and cell death such as IFV and certain CoV , may not cause prolonged inflammation due to strong induction of antiviral clearance. These infections, however, cause massive damage and cell death to the epithelial barrier, so much so that areas of the epithelium may be completely absent post infection . Factors such as RANTES and CXCL10, which recruit immune cells to induce apoptosis, are strongly induced from IFV infected epithelium . Additionally, necroptotic factors such as RIP3 further compounds the cell deaths in IFV infected epithelium Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: IFV, usually result in severe acute exacerbations with non-classical symptoms of chronic airway inflammatory diseases. Fortunately, annual vaccines are available to prevent IFV infections ; and it is recommended that patients with chronic airway inflammatory disease receive their annual influenza vaccination as the best means to prevent severe IFV induced exacerbation. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: eosinophilic infiltration in the asthmatic airway. The effect is also further compounded by the participation of Th1 and ILC1 cells in the COPD airway; and Th2 and ILC2 cells in the asthmatic airway. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: that aid in the proper function of the motile cilia in the airways are aberrantly expressed in ciliated airway epithelial cells which are the major target for RV infection . Such form of secondary cilia dyskinesia appears to be present with chronic inflammations in the airway, but the exact mechanisms are still unknown . Nevertheless, it was found that in viral infection such as IFV, there can be a change in the metabolism of the cells as well as alteration in the ciliary gene expression, mostly in the form of down-regulation of the genes such as dynein axonemal heavy chain", "Title: Mapping the drivers of within-host pathogen evolution using massive data sets\nPassage: We avoid considering lower quantiles due to potential biases which would be induced by drug/HLA specific sample sizes. We then perform hierarchical clustering on assigned selection classes using hclust , using the complete linkage method. The resultant dendrograms for drug associated selection are shown in Supplementary Figure 13 . Title: K-Pax2: Bayesian identification of cluster-defining amino acid positions in large sequence datasets\nPassage: The above criteria led to the discovery of 23 core clusters among the 57 clusters present in the K-Pax2 output. Title: Visual tools to assess the plausibility of algorithm-identified infectious disease clusters: an application to mumps data from the Netherlands dating from January 2009 to June 2016", "Passage: A major challenge with clustering algorithms is to balance specificity and sensitivity. If an algorithm lacks specificity, it finds clusters of cases even though there are no transmission events that link them. If it lacks sensitivity, the algorithm does not find genuine transmission chains. To be on the safe side, most algorithms have a high sensitivity at the expense of specificity and as a result also identify clusters of cases that are not genuine transmission clusters. We therefore propose cluster detection using algorithms as a two-step process: detecting possible clusters of infectious diseases with an algorithm and assessing the plausibility Title: Visual tools to assess the plausibility of algorithm-identified infectious disease clusters: an application to mumps data from the Netherlands dating from January 2009 to June 2016", "Passage: of which five are nested . After collapsing the nested clusters into their parent clusters, five significant highest unnested clusters remain. Of those five highest unnested clusters clusters, cluster 2 , 3 and 4 contain smaller clusters which are also significant, whereas cluster 1 and 5 are not supported by other significant clusters at a lower nesting level.", "Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings\nPassage: The PATH and the CDC laboratories both used the CDC-validated real-time RT-PCR assays specific for each target microbe in this study. Oligonucleotide primers and probes were procured from IDT . Real time PCR has previously been described as an effective method by which to assess the performance of extraction methods in that it is highly specific, it can detect very low levels of target and can indirectly inform on the purity of extracted samples . The core amplification reagent used in all real time RT-PCR assays was qScript XLT 1-Step RT-qPCR ToughMix . All reactions were conducted in 20 \u03bcL Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase", "Passage: To further demonstrate the flexibility of the new RT-qPCR method to variants, we performed a comparison between the new method and the conventional RT-qPCR method. To increase the comparability, the forward primer of the conventional method shares identical sequence with the HFman probe, and an additional TaqMan probe was designed for the conventional method. For the wild template, although the curve of the new method appeared slightly earlier and had stronger fluorescent signal than that of the conventional method, the amplification curves produced by both methods are close to each other , supporting the idea that both methods are comparable. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Apart from the commonly used RT-PCR in diagnosing MERS-CoV, four studies identified various diagnostic methods such as reverse transcription loop-mediated isothermal amplification , RT-insulated isothermal PCR and a one-step rRT-PCR assay based on specific TaqMan probes. RT-LAMP has similar sensitivity as real time RT-PCR. It is also highly specific and is used to detect MERS-CoV. It is comparable to the usual diagnostic tests and is rapid, simple and convenient. Likewise, RT-iiPCR and a one-step rRT-PCR assay have also shown similar sensitivity and high specificity for MER-CoV. Lastly, one study focused on the validation of the six commercial real RT-PCR kits, Title: A novel quantitative PCR mediated by high-fidelity DNA polymerase", "Passage: All 7 samples were detected as positive by the new method, while only 4 were detected as positive by the conventional method , possibly due to low viral load. This result suggested that the HFman probe-based RT-qPCR has higher sensitivity than the TaqMan probe-based conventional RT-qPCR.", "Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant\nPassage: She presented 1 month later with 5 days of upper respiratory tract infection symptoms, fever, headache, and a rapidly progressive right-hand weakness with normal alertness. She had normal blood pressure . She was started on cefotaxime, vancomycin, and acyclovir. White cell count was 13.4 \u00d7 10 9 /L, hemoglobin was 7.8 g/L, and platelets were 239 \u00d7 10 9 /L. While in the MRI machine she deteriorated with vomiting and reduced level of consciousness . Brain MRI showed a rapid progression over a few sequences of an active bleed involving both superficial and deep gray matter as well as subcortical Title: Muscle weakness associated with H7N9 infection: report of two cases", "Passage: that lesions had shrunk . Cough and other symptoms also alleviated gradually, and finally, she began absorbing oxygen via venturi mask one month later. The last chest CT scan was token on day 80 , and another 10 days later, she was discharged with a slight cough and expectoration and with no significant dry and wet rales heard. Her upper limb proximal muscle strength was measured at level 2/5, distal parts at level 4/5, and lower limb muscle strength at level 2/5. Title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus", "Passage: Cerebrospinal fluid analysis and an electroneuromyogram were performed on fourth and fifth days after neurological symptom onset, respectively; the results were within normal limits. The electroneuromyogram was repeated on the 15 th day of neurological symptoms, but no significant abnormalities were noted despite the persisting weakness in the patient's left leg and arm. During the treatment with IVIG, the patient presented with transient worsening of her hemiparesis, but progressively recovered over the course of weeks after discharge from the hospital. At 32 days post-neurological symptom onset , a physical exam revealed significant improvement of muscular strength and abolished deep tendon Title: Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant", "Passage: After discharge, the patient was started on regular transfusion exchange. Six months later, the patient was diagnosed to have Crohn's disease and primary sclerosing cholangitis. Two years later, the patient still suffers right hemiparesis but is able to walk without support. She presents an expressive aphasia. Her intellectual abilities are average, or below the mean but in the normal range, except for the speed of information processing, verbal working memory, and some elaborated executive functions.", "Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome\nPassage: Text: Severe acute respiratory syndrome coronavirus , a member of the genus Betacoronavirus within the family Coronaviridae, is an enveloped virus with a single-stranded positive-sense RNA genome of approximately 30 kb in length. The 5 two-thirds of the genome encodes large polyprotein precursors, open reading frame 1 and ORF1b, which are proteolytically cleaved to generate 16 non-structural proteins . The 3 one-third of the genome encodes four structural proteins, spike , envelope , matrix and nucleocapsid , and non-structural proteins, along with a set of accessory proteins . SARS-CoV is the etiological agent of SARS . At least 8,098 laboratory-confirmed Title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 \u00c5 resolution", "Passage: and symmetrical relationships between GP and the matrix protein VP40 in the envelope, and the underlying nucleocapsid layer . Title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 \u00c5 resolution\nPassage: generated by projection matching, using methods similar to those previously used with other viral spikes within their envelopes 4,40 . The main difference was the use of \"T\"-masked images for two-dimensional analysis and alignment, and unmasked images to apply the alignment parameters to generate new image averages. In addition a cylindrical mask was used on the 3-D reference volume. In both cases, the 2-D and 3-D masks selected data from the envelope and spike, and suppressed noise from adjacent spikes, as illustrated in Supplementary Figs S2 and S3 . Title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 \u00c5 resolution", "Passage: shape . While our structure shows a spike length of 13 nm and a stalk length of 5 nm and width of 3.5 nm, the tomographic structures show a spike length of 14 nm, with a more pinched, shorter and more narrow stalk region of 2.5 nm in length and 3 nm width, while the virion envelope at the base also appears to be sloped away from the GP stalk . Our structure clearly delineates the 5 nm bilayer of the virion envelope as well as the alpha helices of the heptad repeat domains and the nub feature at the", "Title: Prevalence and associated factors of pediatric emergency mortality at Tikur Anbessa specialized tertiary hospital: a 5 year retrospective case review study\nPassage: The top causes for neonatal deaths were late-onset sepsis and meningitis , while in infants, pneumonia and congestive heart failure were the main causes of death. This was similar in the preschool age children with pneumonia at 26.7% and congestive heart failure at 16%. On the other hand, congestive heart failure was the most common cause of death for the school age group, followed by pneumonia and hematological malignancy. There were no neonatal cases of tuberculosis, renal failure, abdominal mass and hematological malignancy . Title: Prevalence and associated factors of pediatric emergency mortality at Tikur Anbessa specialized tertiary hospital: a 5 year retrospective case review study", "Passage: and diarrhea account for 20% of deaths in children fewer than 5 years old . Malaria, AIDS, acute respiratory-tract infection, measles, and malnutrition were significantly contributed to child mortality . In developing countries 10 to 20% of severely sick children are admitted to hospital every year . Title: Pneumonia in Bhutanese children: what we know, and what we need to know", "Passage: Focusing on data collected under the term \"pneumonia\", this disease was ranked as the fifth main cause of mortality among the Bhutanese population in 2017 . The estimates of deaths for different major causes in Bhutanese children between one and 59 months of age showed a Table 5B ). However, pneumonia remains the single biggest cause of post-neonatal child deaths, causing 27\u00b78% of the overall number of deaths in 2010 . A hospitalbased study conducted between 2009 and 2011 collected causes of under-five mortality in Bhutan. Authors reported that pneumonia accounted for 45% of deaths in children from one to Title: Pneumonia in Bhutanese children: what we know, and what we need to know", "Passage: In 2015, pneumonia was ranked as the single biggest killer of post-neonatal children worldwide. With an estimated 15\u00b75% attributable fraction of all deaths in children under 5 years of age, pneumonia is believed to be responsible for the deaths of around 900,000 children every year . The main burden remains disproportionately concentrated in low-and middle-income countries in Southeast Asia and sub-Saharan Africa, where pneumonia is one of the most frequent triggers of health facility consultation, and one of the most common causes of hospitalization, representing a huge load for the overburdened and fragile health care systems .", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: 2 days to be hospitalised. Title: Estimating the number of infections and the impact of non-\nPassage: estimate that interventions across all 11 countries will have averted 59,000 deaths up to 31 March Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.", "Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic\nPassage: Postseason antibody testing was performed on samples collected at the next blood donation visit, and only donors with such samples were considered evaluable for infection. Seroconversion was defined as \u22654-fold increase in HI or NI titer. We followed standard criteria for vaccine seroconversion also used in some studies of infection , under which an increase from <1:10 to 20 does not qualify as 4-fold. Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: We found only 1 instance of seroconversion among the 87 participants , each of whom had 2 serum samples taken for antibody measurement. Miller et al. reported that 89.1% of participants with pandemic 2009 had an antibody titer of >32 three weeks after infection, although a baseline serum sample was not taken; therefore, seroconversion could not be demonstrated . None of the participants with positive PCR results reported taking NIs, and all had serum samples taken >2 weeks after the positive nose swab specimen, allowing suffi cient time for seroconversion. Our results are likely to be true positives, as all Title: Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection", "Passage: By measuring antibodies against FeLV p45 and whole virus by ELISA, seroconversion was observed in one cat. In the p45 ELISA, this cat had a positive response throughout weeks 8 to 20 with a peak of 26% of the positive control at week 14, and throughout weeks 4 to 20 with a peak of 54% of the positive control at week 20 in the FeLV whole virus ELISA . Analysis of the remaining animals showed no statistically relevant difference between the groups in p45 as well as whole virus ELISA . Prior to challenge, all samples were negative for the Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: plus enhanced surveillance that has detected a substantial number of mild or asymptomatic infections. 63 Outside hospital, the burden of disease is likely to be larger than has been reported. 66 Serological analysis of several UK patients found a rapid rise in antibodies from day 10, and that titres were maintained for at least 300 days post-infection. Anti-S antibodies are responsible for virus neutralisation. Importantly for serological analyses, patients who experience only mild disease may mount only a modest serological response. 67 Sequential samples from three cases involved in a chain of transmission were extensively analysed using next-generation sequencing. 68", "Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines\nPassage: Antigen-presenting cells in LN then maintain the homeostasis of LN themselves and activate adaptive immune responses. In the last decades, the long-held paradigm of migratory DCs, resident in peripheral tissues as the skin, as unique APCs involved in T cell immunity has dramatically changed. Indeed, CD169 + subcapsular sinus macrophages, medullary macrophages, and LN-resident DCs are LN sentinels that avoid excessive pathogen dissemination and mediators of immune responses . Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines", "Passage: Dendritic cells are the primary professional antigen-presenting cells that reside in both lymphoid and non-lymphoid organs . DCs encompass several heterogeneous subsets whose subdivision relies on ontogeny, expression of surface-receptors, and transcription factors . Much effort has been done in the identification and characterization of tissue-specific DC subsets to unravel the correlation between phenotype, localization, and functional properties, both in health and disease. Initially, DCs have been classified into conventional DCs and plasmacytoid DCs . Briefly, cDCs prime na\u00efve T cells and orchestrate ag-specific adaptive responses, while pDCs intervene during viral infections producing type I interferons . Advanced approaches have Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines", "Passage: Concerning migratory DCs and considering the skin, which represents the site of utmost importance for vaccination strategies due to the ease accessibility and the extremely high presence of DCs, skin-resident DCs have been subdivided into epidermalresident Langerhans cells , which are Langerin + and two diverse subsets of dermal DCs: Langerin + CD103 + and Langerin \u2212 CD103 \u2212 . Upon infection, dDCs migrate to the LN within 10-24 h while LCs within 48-72 h, supporting long-lasting ag-presentation. Several works reveal the intrinsic differences between the two subsets in inducing Th or CTL responses, due to the particular cross-presenting capabilities Title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines\nPassage: subcutaneous, intradermal, and intramuscular immunization , thus permitting an extremely fast uptake by phagocytes strategically localized in close proximity to the subcapsular sinus or lymphatic sinus of draining LN .", "Title: Quantifying social distancing arising from pandemic influenza\nPassage: social distancing. Title: Quantifying social distancing arising from pandemic influenza\nPassage: It is possible that other interventions, such as closing schools and quarantining infectives, played a role in containing the epidemic. We argue that most of these can be broadly categorized as social distancing. Measures such as quarantine are likely to have been practised more or less constantly throughout the epidemic and probably did not contribute to the changes in R. Title: Quantifying social distancing arising from pandemic influenza\nPassage: thus discouraging people from getting out and circulating in the wider population . Title: Estimating the number of infections and the impact of non-\nPassage: Social distancing Avoid social interaction wherever possible", "Title: Host resilience to emerging coronaviruses\nPassage: Both viral infections elicit a very strong inflammatory response, and are also able to circumvent the immune response. There appears to be several ways that these viruses evade and otherwise redirect the immune response . The pathways that lead to the induction of the antiviral type I interferon response are common targets of many viruses, and coronaviruses are no exception. SARS-CoV and MERS-CoV are contained in double membrane vesicles , that prevents sensing of its genome . As with most coronaviruses several viral proteins suppress the type I IFN response, and other aspects of innate antiviral immunity . These alterations Title: Adenovirus flow in host cell networks", "Passage: DNA receptors and RIG-I-like receptors. The detected signal may be a cell-bound virus, a viral genome in the midst of a carrier process, or any molecule that gets released or secreted from damaged or dying cells . Stimulation of a given sensory receptor triggers a cascade of tens or even hundreds of proinflammatory proteins that together orchestrate the early response to infection, and also play a role in activation, maturation and shaping of the adaptive immune response. In addition to the PAMP-recognition system, the cell can also detect host-derived antibody that gets internalized along with virus during cell entry . Title: Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins", "Passage: Even among non-immune cell lines RV infection efficiency differs dramatically, although our data using a pseudotype virus system shows that non-immune cells are generally susceptible to RV. These data suggest that the permissibility to RV infection differs considerably among non-immune cell lines. One possible factor modulating the RV infectivity is the host innate immune system. RV is highly sensitive to interferon 3, 47, 48 , and the infectivity of individual cell lines with RV is affected by their capacity for IFN production and response to IFN. Vero cells are defective in IFN production 49, 50 , and JEG3 and JAR Title: Innate Immune Sensing and Response to Influenza", "Passage: These factors directly interact with the virus inside host cells to restrict the entry, replication, and assembly of virus, thereby rendering the cells nonpermissive to virus. This form of immunity to virus is referred as intrinsic antiviral immunity . These factors are preexistent, but can be further enhanced by viral infection and type I IFNs, the principal mediator of antiviral innate response.", "Title: Key Gaps in the Knowledge of the Porcine Respiratory Reproductive Syndrome Virus (PRRSV)\nPassage: N protein is involved in several mechanisms for immune evasion and is also one of the most immunogenic structural proteins . Antibodies against N appear early during acute infection, together with those against M and GP5 proteins, but are non-neutralizing and could be involved in antibody dependent enhancement . Title: Resolution of the cellular proteome of the nucleocapsid protein from a highly pathogenic isolate of porcine reproductive and respiratory syndrome virus identifies PARP-1 as a cellular target whose interaction is critical for virus biology", "Passage: 3.1. Pull-down of cellular interacting proteins N protein was expressed with a C-terminal His-tag in BL21pLyS cells . To purify the N protein bacterial lysate from the induced culture was incubated with nickel affinity beads. Western blot analysis using anti-his antibody indicated that N protein bound to the nickel affinity beads . The same was also shown for the UBC9 protein used as a binding control . Title: Resolution of the cellular proteome of the nucleocapsid protein from a highly pathogenic isolate of porcine reproductive and respiratory syndrome virus identifies PARP-1 as a cellular target whose interaction is critical for virus biology", "Passage: more represents a working threshold for assigning specific from non-specific interactions that arise due to binding to either the matrix or the single chain EGFP antibody component of the GFP-trap . Cellular interacting proteins exhibiting ratios of a conservative value of 4-fold or greater were therefore considered to potentially represent specific interacting partners of the N protein. This resulted in the identification of 108 proteins that could potentially interact with N protein either individually or as part of larger protein complexes . These proteins were used in downstream analysis. Title: High Fidelity Processing and Activation of the Human \u03b1-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3", "Passage: The proHNP1 cDNA sequence encoding the natural 75 amino acid residue sequence extended by 5 amino acids at the N-terminus was amplified using oligonucleotides and with plasmid PEC2081 as template. EcoRIand XhoI-digested DNA was ligated into pET28a+ vector to generate plasmid PEC2129 which encodes proHNP1 with a 41 amino acid residue N-terminal sequence containing the His 6 -tag . The plasmid was used to transform Escherichia coli BL21, generating strain PEC2132-1 which was used for expression and purification of His 6 -proHNP1.", "Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: to define two major genotypes or groups, A and B, which are further classified into four subgroups . HMPV A2, the most frequently observed subgroup, is further divided into two proposed sub-lineages . Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: used to define two major genotypes or groups, A and B, which are further classified into four subgroups . HMPV A2, the most frequently observed subgroup, is further divided into two proposed sub-lineages . Title: Consensus and variations in cell line specificity among human metapneumovirus strains", "Passage: Recently, epidemiological survey studies by PCR have detected the unique 180nt-dup and 111nt-dup in the G gene of A2b subtype HMPV strains . At the Virus Research Center, Sendai Medical Center, Japan, varieties of respiratory viruses have been routinely isolated using a microplate system harboring several types of cell lines . A2b subtype HMPV strains were isolated from 86 patients between 2014 and 2016 . Among the 86 patients, 41 patients in different seasons or locations were selected, and the nucleotide sequences spanning the G gene of HMPV strains in these patients were directly determined using the clinical samples. From Title: Consensus and variations in cell line specificity among human metapneumovirus strains", "Passage: Barcelona city, Spain . These data showed that all the A2b 180nt-dup and A2b 111nt-dup strains detected in different areas are closely related to one another. Six HMPV A2b strains without nt-dup duplication in the G gene strains) were also observed in this cluster . To obtain the highest resolution of phylogenetic relationships of subtype A2b strains, a phylogenetic analysis of the full-length genome sequences was performed. Subtype A2b HMPV strains, which were subjected to fulllength genome sequencing in this study, are listed in Table 1 . The full-length genome sequence of hMPV/Sendai/0256/2015 was successfully determined directly from the clinical", "Title: Patterns of Positive Selection in Six Mammalian Genomes\nPassage: more similar to it than the two orthologs Title: An object simulation model for modeling hypothetical disease epidemics \u2013 EpiFlex\nPassage: What is most notable in Figure 7 is the relationship between the rough sine wave form of the classically derived SIRP once the initial startup period is over for influenza, a repeating wave develops that is similar in overall shape and variability to real world data such as those for Milwaukee, at a roughly similar scale. These two graphs refer to populations that differ in size by about 1 order of magnitude . We can also see a similar number of peaks. Owing to the need to compare these two graphs natively, these two figures are not optimum. However, they Title: Lost in Translation (LiT)", "Passage: Studies of intact healthy, unrestrained animals with telemetry monitoring of vital functions are of growing importance as is the drive to move into man much earlier, provided there is adequate safety coverage. The physiology of the cardiorespiratory system has translated to man reasonably well, the gastrointestinal tract of rodents has significant differences from man, the immune system of mice has large differences from man . The higher cognitive and reasoning facilities of rodents have limited translation to man. The most widely explored cross-species biochemical systems comparison has been of plasma lipids. Unsurprisingly, non-human primates have the closest resemblance, and rabbits Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity .", "Title: Composition and dynamics of the respiratory tract microbiome in intubated patients\nPassage: The OP community was sampled by placing a sterile Copan FLOQSwab against the posterior oropharynx along the external margin of the endotracheal tube. ET samples were collected via the endotracheal tube's inline suction catheter. After flushing the suction catheter with approximately 5 mL of sterile saline, the catheter was advanced into the distal trachea and approximately 5 mL of sterile saline was flushed into the trachea and suctioned back into a Lukens trap. All samples were stored immediately on ice and transferred to \u221280\u00b0C storage within 60 min of collection. Title: Isolation and characterization of microparticles in sputum from cystic fibrosis patients", "Passage: Bacterial species in sputum specimens were identified accordingly to the North-American guidelines . Sputum samples were directly spread-out in selective media, such as MacConkey agar for Pseudomonas aeruginosa and Alcaligenes xilosoxidans, manitol salt agar for Staphylococcus aureus, and BCSA for Burkholderia cepacia complex, and incubated at + 36 \u00b1 1\u00b0C for a period of 18-72 h. Colonies were quantified and identified by classical phenotypical tests. Title: Composition and dynamics of the respiratory tract microbiome in intubated patients", "Passage: Fifteen subjects were enrolled from the medical intensive care unit of the Hospital of the University of Pennsylvania. Initial sample and data collection was performed within 24 h of intubation, with subsequent collection performed at 48-to 72-h intervals thereafter for the duration of mechanical ventilation. Sampling was performed by oropharyngeal swab and endotracheal aspirate. Informed consent was obtained from subjects themselves or a patient surrogate. The protocol was reviewed and approved by the University of Pennsylvania IRB . Healthy controls were non-intubated volunteers without underlying lung disease sampled by OP swab and bronchoscopic bronchoalveolar lavage and have been previously described Title: Automated TruTip nucleic acid extraction and purification from raw sputum", "Passage: Clinical sample characteristics are summarized in S1 Table. Nine samples were both smear negative and culture negative, so these nucleic acid extraction and PCR amplification results are not included in the final analysis . Sputum samples ranged from saliva-like to hemoptoic , with most samples characterized as mucoid or mucopurulent . One of the AFB smear positive , solid culture positive sputum samples was consumed in its entirety during NALC-NaOH decontamination, leaving 123 sputum extracts and 124 sediment extracts for automated nucleic acid extraction.", "Title: A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe\nPassage: Of the top 100 human pathogens identified, 42 were either included in the GBD , or are reportable to the EC , or both. Reasons for failure to include pathogens may be that pathogenic agents cause rarely diagnosed disease , or because disease agents are diverse, e.g. pneumonia or other lung infections and gastro-intestinal symptoms or GI-tract infections . The impact of chronic disease or diseases causing low morbidity may be difficult to quantify or seen as less important . In addition, some pathogens may generally be commensals or natural biota or species existing in the environment causing opportunistic infections Title: A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe", "Passage: Two lists each including the top 100 human and domestic animal pathogens which cause significant clinical disease and which therefore need consideration from a health and well-being perspective were short-listed using the Hindex prioritisation method ). When combined, 114 pathogens appeared solely in the human or animal list, and 43 were in both lists. Of the top 100 human pathogens, 66 were classed as zoonotic and 67 were emerging, compared to 67 and 57 for domestic animal pathogens, respectively. Title: One Health in China", "Passage: It has been reported that 1,415 species of infectious organisms have been identified to be pathogenic to humans. Among these organisms, 868 are zoonotic, which may be transmitted between humans and animals . Of the emerging pathogens, 132 pathogens are zoonotic, and zoonotic pathogens are twice as likely to be associated with emerging diseases compared with nonzoonotic pathogens . There are 43 infectious diseases, such as SARS, MERS, H5N1, H7N9, Ebola, and Marburg that have newly emerged worldwide since the 1970s . Twenty of these diseases were found in China. In addition, reemerging diseases, such as rabies, pulmonary tuberculosis, and Title: Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations", "Passage: Using the Global Infectious Diseases and Epidemiology Network , we compiled a dataset on pathogen richness in the corresponding 43 geographic regions . It consists of 95 diseases caused by 168 extracellular pathogens, including diverse bacterial species, fungi, protozoa, and helminthes. Using the same protocol, we additionally compiled a dataset on the prevalence of 149 diseases in the same regions caused by 214 viral and other obligate intracellular pathogens. The dataset and methodology employed for the analysis are standardized and have been used previously in similar contexts .", "Title: Influenza virus-related critical illness: prevention, diagnosis, treatment\nPassage: in combination with oseltamivir versus oseltamivir monotherapy in hospitalized influenza patients is currently enrolling participants . Title: Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine\nPassage: The first global pandemic of the 21st century was announced by the World Health Organization in 2009 due to the worldwide spread of influenza A subtype H1N1 . More than 214 countries have reported laboratory confirmed cases, and more than 18,449 deaths have been recorded . Currently, the neuraminidase inhibitor TamifluH remains the primary drug prescribed to patients infected with H1N1/09 . However, the emergence of drug resistant viral strains and limited drug administration window exemplifies the need for additional therapies. Title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus", "Passage: lethal dose of pandemic H1N1 IAV; interestingly, this inhibitor significantly out-performed the clinically recommended oseltamivir in these studies . Title: Progress of small molecular inhibitors in the development of anti-influenza virus agents\nPassage: A novel highly potent oral drug candidate AV5080 . The N-substituted Oseltamivir analogues displayed enhanced inhibition against NA from Oseltamivir-resistant and wild-type strains . Jin-Hyo Kim et al synthesized a series covalent NA inhibitors by introducing the strong electronegative fluorine atom at core-ring of Zanamivir and Oseltamivir ; and these compounds showed excellent antiviral activity in vitro. Compound 27 showd IC50 values of 1 nM and 10 nM agaisnt B/Perth/211/01 and A/Fukui/45/01 H3N2 in plaque size reduction assays, superior than those for Zanamivir . These compounds also showd comparable inhibition levels in animal models .", "Title: Exposure science in an age of rapidly changing climate: challenges and opportunities\nPassage: . As noted above, the 2015 ISES Meeting was an important motivation for this paper and for the case study topics presented. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: This study was approved by the Massey University Human Ethics Committee: Southern A . Written informed consent was obtained from all participants. Title: A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan\nPassage: sample material. Title: Identification of antigens presented by MHC for vaccines against tuberculosis\nPassage: Further information on research design is available in the Nature Research Reporting Summary linked to this article", "Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection\nPassage: A conclusion of several evaluations of the specificity of WHO's 1999 clinical case definition for influenza was that the definition needed to be revised to enhance its specificity for influenza detection. In 2010, only 31 of the 105 countries that participated in a WHO survey of national influenza centres reported using this definition. 15 An earlier investigation of influenza surveillance across western Europe had revealed that case definitions varied between countries. 16 In a global consultation in 2011, WHO outlined how influenza surveillance should allow influenza seasonality to be evaluated in each country and allow the start of the influenza Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection", "Passage: definitions for infection with the human immunodeficiency virus and acquired immunodeficiency syndrome were revised multiple times between 1982 and 2014, to reflect new knowledge about the syndrome and the isolation of the virus and to include laboratory testing. 8 In the revision of any case definition there needs to be careful deliberation over how the available relevant evidence can help balance the sensitivity and specificity of the definition in such a way that the objectives of any related surveillance can be met. In 2011, the World Health Organization launched an initiative to develop global standards for influenza surveillance, including a Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection", "Passage: also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden. Title: Global epidemiology of avian influenza A(H5N1) virus infection in humans, 1997 \u2013 2015: a systematic review", "Passage: The WHO case definition was used. 58 A confirmed case was defined as a human case of influenza A virus infection reported by WHO and with laboratory confirmation, i.e. a patient with defined clinical signs, epidemiological linkage and laboratory confirmation by an influenza laboratory accepted by WHO, as specified in the WHO case definition. Other reported cases were considered as probable cases if they had exposure to other confirmed human cases, or to sick or dead poultry, or the H5N1 infection was confirmed by the country or local institutions but not meeting WHO criteria or announced by WHO.", "Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: Spain 15% Title: Estimating the number of infections and the impact of non-\nPassage: 45. Wikipedia. 2020 coronavirus pandemic in Spain. Wikimedia Foundation Title: Estimating the number of infections and the impact of non-\nPassage: Spain measures cough or fever symptoms.47 17/3/2020", "Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires\nPassage: B cell receptor diversity within the na\u00efve B cell compartment results from the recombination of the variable , diversity , and joining genes in the heavy chain and VJ genes in the light chain during B cell maturation. During an infection, na\u00efve B cells are exposed to antigen in the secondary lymphoid organs and undergo activation and differentiation including somatic hypermutation and immunoglobulin class switching to produce high affinity Abs. Ag-activated B cells may undergo differentiation into Bmem or short and long-lived PCs. The differentiation into Bmem may occur with or without T cell help and in a germinal center Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: rearrangement during B cell differentiation was responsible for antibody diversification . The subsequent explosion of available monoclonal antibodies led to revolutionary diagnostic, therapeutic, and research reagents to distinguish different types of immune cells . Together, these discoveries have allowed us to probe humoral immunity at the level of the antigen-specific B cell. Title: Techniques to Study Antigen-Specific B Cell Responses\nPassage: during B cell differentiation was responsible for antibody diversification . The subsequent explosion of available monoclonal antibodies led to revolutionary diagnostic, therapeutic, and research reagents to distinguish different types of immune cells . Together, these discoveries have allowed us to probe humoral immunity at the level of the antigen-specific B cell. Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires", "Passage: wild-type strain of S. pneumoniae which allowed the vaccination to elicit a memory response. Furthermore, the studies also revealed that the Ab repertoire across individuals was oligoclonal based on their limited usage of VH and VL families and similar H and L pairing for specific serotypes. Two studies identified IgG2 and IgA H chains matching the Ab isotype and response found in the donor sera indicating that the Fabs and Abs derived were from a response to S. pneumoniae infection . Further characterization of the full-length fully human serotype-specific mAbs revealed a preferential use of lambda over kappa light chains", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: While poxvirus-vectored vaccines have not yet been approved for use in humans, there is a growing list of licensed poxvirus for veterinary use that include fowlpox-and canarypox-vectored vaccines for avian and equine influenza viruses, respectively . The fowlpox-vectored vaccine expressing the avian influenza virus HA antigen has the added benefit of providing protection against fowlpox infection. Currently, at least ten poxvirus-vectored vaccines have been licensed for veterinary use . These poxvirus vectors have the potential for use as vaccine vectors in humans, similar to the first use of cowpox for vaccination against smallpox . The availability of these non-human poxvirus Title: Avipoxviruses: infection biology and their use as vaccine vectors", "Passage: In the poultry industry, prophylactic measures against FWPV are achieved primarily by vaccination with live FWPV or antigenically similar pigeonpox virus strains produced in CEF cells . In the past two decades, numerous outbreaks have been reported in vaccinated flocks, suggesting that vaccines used against the disease were not effective. In the United States a commercial FWPV vaccine was shown to be contaminated with REV and caused lymphoma among broiler chickens . It has been shown that sequences of REV have been integrated into the DNA of FWPV vaccines as well as in field FWPV isolates . The integration site Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Poxvirus vaccines have a long history and the notable hallmark of being responsible for eradication of smallpox. The termination of the smallpox virus vaccination program has resulted in a large population of poxvirus-na\u00ef ve individuals that provides the opportunity for the use of poxviruses as vectors without preexisting immunity concerns . Poxvirus-vectored vaccines were first proposed for use in 1982 with two reports of recombinant vaccinia viruses encoding and expressing functional thymidine kinase gene from herpes virus . Within a year, a vaccinia virus encoding the HA of an H2N2 virus was shown to express a functional HA protein and Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is strong safety and efficacy data for use of NYVAC or MVA-vectored influenza vaccines, preexisting immunity remains a concern. Although the smallpox vaccination campaign has resulted in a population of poxvirus-na\u00ef ve people, the initiation of an MVA or NYVAC vaccination program for HIV, influenza or other pathogens will rapidly reduce this susceptible population. While there is significant interest in development of pox-vectored influenza virus vaccines, current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains. This would likely limit the use and/or efficacy of poxvirus-vectored influenza virus vaccines for regular and seasonal use", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: Intranasal therapy with carrageenan and Zanamivir starting 72 hpi significantly protects lethally influenza H1N1pdm infected mice Next, the minimal effective dose of Zanamivir used as mono-therapy was evaluated in a lethal H1N1pdm mouse model, following the same scheme as described in the H7N7 experiments. The lowest effective dose of Zanamivir after a treatment start 24 hpi was 1 mg/kg BW/ day and its combination with carrageenan was highly effective . In the following experiment the therapeutic potential of the combination with a therapy start 48 or 72 hpi was investigated in comparison with the respective placebo treatment. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: contrast, the combination therapies led to 50% and 90% survival, depending on the Zanamivir concentration. Statistical analysis showed that the Zanamivir mono-therapy 1 mg/kg BW/day did not show a significant benefit , whereas the mono-therapy with 3 mg/kg BW/day significantly increased the survival rate compared with placebo treated mice . Both Zanamivir concentrations experienced significant benefit in survival by the combination with carrageenan . Similarly, the combination therapies resulted in remarkably increased survival when compared to the carrageenan mono-therapy. No statistically significant difference was observed between the combination containing 3 mg/kg BW/day Zanamivir and that containing 1 mg/kg BW/day . Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: The finding supports the development of the Zanamivir and carrageenan combination approach. As the intranasal treatment regime is incapable to effectively treat virus infections of the lung, the primary target of such a product is the prophylaxis and therapy of uncomplicated influenza. Since the majority of influenza infections causes uncomplicated illnesses and practically all cases of influenza start with an infection of the nasal cavity or the upper respiratory tract, the therapeutic potential is huge. However, clinical studies are required to elucidate and demonstrate the potential of the proposed combination therapy. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: First, we determined the minimal effective dose of a Zanamivir mono-therapy that significantly improved survival time of H1N1 and H7N7 infected mice. For the H7N7 lethal infection the minimal effective dose of Zanamivir as mono-therapy ranged between 1 and 3 mg/kg BW/ day . Next, we compared the antiviral activity of carrageenan and Zanamivir mono-therapies with the respective combination versus placebo treatment. Survival rates of mice with treatment starting 24 hpi are shown in Fig 2A. All placebo treated mice died between day 7 and 9 and also in all mono-therapy groups 100% lethality was observed until day 15. In", "Title: Detection of Acute HIV-1 Infection by RT-LAMP\nPassage: Although the LAMP method is attractive for the development of a rapid POC NAAT, the HIV-1 RT-LAMP assay may also be useful in select laboratory settings, because of the quicker turnaround time and lower cost compared to current laboratory NAAT platforms. The HIV-1 RT-LAMP assay is estimated to cost 15-40X less per test compared to APTIMA, depending on the individual laboratory cost for purchasing the APTIMA kit. In relation to the viral load for each seroconversion panel member, RT-LAMP exhibited the expected limit of detection for the assay, which is approximately 10 4 RNA copies/ mL. Additionally, RT-LAMP had a Title: Detection of Acute HIV-1 Infection by RT-LAMP", "Passage: Ongoing studies involve the evaluation of single-use, disposable heating devices with lyophilized RT-LAMP reagents for detection of HIV from whole blood specimens. Another limitation of the current study is that the assay was specifically designed for detecting subtype B HIV infections, since the primary focus of our laboratory is detection of HIV in the US. For global use, a group M-conserved RT-LAMP assay is preferred. Parallel evaluations of a subtype-conserved RT-LAMP assay are being performed in our laboratory. Title: Detection of Acute HIV-1 Infection by RT-LAMP", "Passage: The LAMP technique has several characteristics that are appealing for the development of a rapid NAAT. The amplification method is highly specific because it requires six primers that recognize eight different sequences in the same target region. The method is less sensitive to biological inhibitors than PCR, which allows for amplification directly from biological samples, such as whole blood, plasma and oral fluid, without the need for extraction of nucleic acid . Amplified material can be detected within 15-60 minutes when incubated at a constant temperature and immediate visual detection is possible due to the large amount of DNA generated Title: Detection of Acute HIV-1 Infection by RT-LAMP", "Passage: to resistance mutations induced by antiretroviral use. For POC use, the RT-LAMP assay may be performed using low-tech, portable heating devices, such as the ESEQuant Tube Scanner or non-instrumented nucleic acid heaters . Similar performance between these devices and traditional thermal cyclers has been demonstrated for the HIV-1 RT-LAMP assay . In the current study, however, a thermal cycler was used as a matter of convenience for large-scale testing.", "Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.\nPassage: Toltrazuril has been marketed for anticoccidial treatment in sheep since the 1980s, and its use has increased during recent years, both in Norway and in the UK . Extensive use of a drug over time may result in decreased efficacy, possibly due to the haploid stages of Eimeria, which immediately select for resistance . Since toltrazuril is the only registered anticoccidial for sheep in several countries, development of resistance in ovine Eimeria species may result in there being few treatment options available for sheep farmers, especially in northern Europe . Diclazuril is an anticoccidial that has been registered for treatment Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.", "Passage: Two lambs were treated orally with trimethoprim/sulphamethoxasole during the first three days of life due to suspected Escherichia coli-infection, from which both recovered within 48 h. Six lambs, two controls and four treated with toltrazuril, developed lameness due to interdigital abscessation, and Streptococcus aureus was detected in two lambs. Four lambs recovered without treatment, and two of the lambs recovered after treatment with benzylpenicillinprocaine administered intramuscularly for three days. Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.", "Passage: rates in different production systems . In contrast, treatment of clinical coccidiosis is considered inefficient due to the extensive intestinal damage already caused by the infection . Loss of sensitivity to toltrazuril, the only anticoccidial registered for use in sheep in the Nordic countries , should therefore be a matter for serious concern for lamb production. Title: Controlled efficacy trial confirming toltrazuril resistance in a field isolate of ovine Eimeria spp.\nPassage: treated and control lambs .", "Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study\nPassage: Information about pre-existing conditions was available for 20 case-patients. Four case-patients had no reported pre-existing conditions or risk factors for severe disease. Pre-existing conditions reported were: morbid obesity/obesity , lung disease , heart disease , pregnancy , diabetes , immunodeficiency , cerebral palsy , prematurity in an infant and genetic disorder . Three case-patients were reported to have more than one pre-existing condition/risk factor. Antiviral therapy was prescribed for 10 case-patients . Antibiotics were prescribed for 10 case-patients . Four case-patients received both antiviral and antibiotic therapy. Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study", "Passage: the importance of pre-existing conditions such as heart disease and obesity is therefore not possible. Onset dates were estimated by reporting parties where information was not available. Finally, these data relate to a small number of cases. Title: Mortality, morbidity and health in developed societies: a review of data sources", "Passage: Studies based on health insurance data can relate to the onset of handicaps, hospital admissions, preventive dental care, etc. Administrative and billing data can be used to study, for example, social inequalities in health or differences in health status between regions. For example, in the USA, Medicare data can be used for comparative effectiveness research on treatments, benefit designs and delivery systems for Medicare beneficiaries , i.e. around 50 million people nationwide . These data permit, for example, national assessments of imaging utilisation and spending for this subpopulation. A French study has used healthcare consumption to compare the health status Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Data on pre-existing conditions were reported for seven cases; five had no pre-existing conditions while one was reported to be obese and one had pre-existing cardiac disease. No data on clinical signs e.g. dyspnea etc. were reported for any of the 38 cases.", "Title: Host resilience to emerging coronaviruses\nPassage: Both viral infections elicit a very strong inflammatory response, and are also able to circumvent the immune response. There appears to be several ways that these viruses evade and otherwise redirect the immune response . The pathways that lead to the induction of the antiviral type I interferon response are common targets of many viruses, and coronaviruses are no exception. SARS-CoV and MERS-CoV are contained in double membrane vesicles , that prevents sensing of its genome . As with most coronaviruses several viral proteins suppress the type I IFN response, and other aspects of innate antiviral immunity . These alterations Title: Temporal trends in the discovery of human viruses", "Passage: implications. Current trends are consistent with a pool of at least 38 undiscovered species that will be reported at an average rate of at least approximately one per year to 2020. In this context, it is worth noting that three new species were reported in 2007: two polyoma viruses, Ki and Wu, and a reovirus, Melaka . Other viruses may have been reported but not yet classified. In practice, future rates of discovery will, of course, be affected by any major advances in virus detection technology or by any major shifts in the effort expended on virus discovery programmes. Tissue Title: Frontiers in antiviral therapy and immunotherapy", "Passage: Opening this CTI Special Feature, I outline ways these issues may be solved by creatively leveraging the so-called 'strengths' of viruses. Viral RNA polymerisation and reverse transcription enable resistance to treatment by conferring extraordinary genetic diversity. However, these exact processes ultimately restrict viral infectivity by strongly limiting virus genome sizes and their incorporation of new information. I coin this evolutionary dilemma the 'information economy paradox'. Many viruses attempt to resolve this by manipulating multifunctional or multitasking host cell proteins , thereby maximising host subversion and viral infectivity at minimal informational cost. 4 I argue this exposes an 'Achilles Heel' that Title: Specialized pro-resolving mediators: endogenous regulators of infection and inflammation", "Passage: Influenza. Viral pathogens also appear to interact with the host in a way that is modifiable by pro-resolving factors. Influenza viruses are a well-suited model to understand the role of resolution mediators and the mechanisms in viral infections, as different strains of the virus elicit varied host immune responses and outcomes. In studies that compare more virulent strains of the influenza virus to less virulent strains, pro-resolving mediators inversely correlated with biological activity of the virus. More virulent strains of influenza led to suppression of lipoxins 98 , which is associated with enhanced viral dissemination. Protectin D1 has pivotal and", "Title: Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification\nPassage: references. The fold threshold for changed protein fold-change ratios was set at \u00b1 1.20, which covers a 95% quantification area based on the normal distribution of two mock samples in all biological replicates 57 . Thus, the proteins with fold-change ratios \u2265 1.20 or \u2264 0.83 were selected as DEPs. Title: Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics", "Passage: bias. Our subcellular and quantitative proteomic analysis workflow is outlined in Figure 2A . Fold changes were calculated by normalizing protein expression in virus-infected cells with corresponding protein expression in mock-infected cells. Venn analysis revealed 1248 common proteins in all infected samples of both technical sets . Based on the Gaussian distribution of the quantitative ratio , we defined the significantly changed ratio threshold as a fold-change of 1.2. We also applied the method used by Barderas et al. and Tan et al., and confirmed the fold induction change \u22651.2 as significant . There were 40 common proteins with fold-changes Title: Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression", "Passage: have the correct identification. Single-and double-hit proteins of the correct identifications were further validated through manual inspections of MS/MS spectra . Quantification of peptides and proteins was performed with XPRESS software, and the peptides with bad quality were not considered by quantification. Finally, we identified nuclear-encoded 1,121 mt proteins that included 313 down-regulated proteins , 201 up-regulated proteins , and 607 not significantly changed proteins. The thresholds of 0.67 represents the 1.5-fold decrease , whereas the threshold of 1.5 represents 1.5-fold increase . Protein abundance ratio smaller than 0.67 or larger than 1.5 were routinely-applied thresholds indicating significant changes in Title: Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses", "Passage: Most of the dysregulated proteins were affected <25%; thus, we considered more stringent parameters and chose fold-change cut-offs of 1.5-fold along with significance. Thus, proteins that were dysregulated >1.5-fold, but not considered significant by either p-value or Z-score, because of a substantial variability in replicate values, were excluded from Viruses 2019, 11, 1028 4 of 16 the subsequent analysis. Using these parameters, we identified 76 proteins that were significantly dysregulated by infection with any of the tested viruses . Five or fewer proteins were significantly dysregulated by RV733 and the pdm09 strains, 15 were dysregulated by PR8, with all but", "Title: Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study\nPassage: Of the 200 enrolled in this study, 25 patients were excluded from the analysis of the data. Of these, 21 patients had incomplete sampling and four patients met exclusion criteria. The characteristics on admission of the 175 patients included in our analysis study group are presented in Table 1 . Mean age was 62 years; roughly one-third had CAP, one-third had HAP, and one-third had VAP. The median hospital and ICU lengths of stay prior to enrolment were six days and nine days , respectively. Title: Development of a tool to assess oral health-related quality of life in patients hospitalised in critical care", "Passage: There are no definitive criteria for the required sample size in a validation study of this kind. However, previous literature suggests that a sample size of 45 to 50 patients should be sufficient for the proposed analysis . Title: Dynamic variations in the peripheral blood lymphocyte subgroups of patients with 2009 pandemic H1N1 swine-origin influenza A virus infection\nPassage: Up to 76 H1N1 outpatients and inpatients were chosen from August to December 2009 in the Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University. Among these, 36 cases were severe and 40 cases were moderate . In addition, 20 healthy volunteers who were not infected with 2009 H1N1 virus, were selected as controls. There were no statistical differences between their ages and genders compared with the H1N1 patients. Title: A Combined Syndromic Approach to Examine Viral, Bacterial, and Parasitic Agents among Febrile Patients: A Pilot Study in Kilombero, Tanzania", "Passage: Patient screening and enrollment. From June 11 to July 12, 2014, a total of 250 patients were screened to determine their eligibility for enrollment. Of these patients, 205 febrile patients were enrolled, including 70 children and 135 adults . All patients enrolled were Tanzanian, and 151 lived on the grounds of the Estate.", "Title: Estimating the number of infections and the impact of non-\nPassage: current trends continue, there is reason for optimism. Title: Gain-of-Function Research: Ethical Analysis\nPassage: there is good reason for such confidence. Title: What Do We Have to Lose? Offloading Through Moral Technologies: Moral Struggle and Progress\nPassage: commitment not met\" . Title: The Large Scale Machine Learning in an Artificial Society: Prediction of the Ebola Outbreak in Beijing\nPassage: infection transfers to another group, new growth will emerge.", "Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity\nPassage: In summary, we find that the presence of viral RNA in the blood and anal swab is positively correlated with the severe disease stage and that early monitoring of virus RNA in blood and the digestive tract on top of the respiratory tract might benefit the disease prediction. Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "Passage: the clinical severe symptom stage. Unfortunately, we missed the earlier time points of patient 1 ) and 3 ) who were directly admitted to ICU on transfer to our hospital because of severe condition, of patient 4 ) who had serum sample collected one day post the diagnosis of severe illness. We, fortunately, observed high serum viral load in serum within their severe illness stage. In the anal swab cohort, we found that the presence of virus RNA in the anal digestive tract was also positively correlated with disease severity . The 3 patients detected with anal virus RNA but Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: We found 15 patients who still carry virus following days of medical treatments. Of these patients, 8 were oral swabs positive , 4 were anal swabs positive , 6 blood positives and 3 serum positives . Two patients were positive by both oral swab and anal swab, yet none of the blood positive was also swabs positive. Not surprisingly, all serum positives were also whole serum positive . In summary, viral nucleotide can be found in anal swab or blood even if it cannot be detected in oral swabs. It should be noted that although swabs may be negative, the Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "Passage: Abstract: The novel coronavirus infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood and the anal swabs . Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity . Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the", "Title: Estimating the number of infections and the impact of non-\nPassage: 2 Results Title: Comparing the outcomes of different postgraduate year training programs in Taiwan\nPassage: All of the 314 trainees participated in the MCQ exam. They were divided into four groups according to their training program. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Results Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: 28 and 60 days after enrollment.", "Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: R\u00e9union Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean . The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance , based on the surveillance system of mainland France . Influenza activity generally increases during austral winter, corresponding to summer in Europe . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: The inclusion phase started on July 21 st and was continued up to week 44, throughout the epidemic wave and beyond. A first serum sample was obtained from each household member. An active telephonic inquiry was then conducted twice a week to record symptoms compatible with influenza-like illness occurring in households. Report of ILI led to three consecutive visits of a nurse to the incident case-dwelling to record symptoms and collect nasal swabs from all family members serum sample was obtained to determine seroconversion rates. Sera were aliquoted and stored at 280uC. Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009\nPassage: subsequent austral winter seasons in 2010 and 2011. Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Statistical analyses were performed with Stata 1 and Excel 1 . Two seasons were defined to identify possible seasonal trends in circulation of the viruses: winter season during weeks 23 to 39 between June and September and summer season during the rest of the year.", "Title: Estimating the number of infections and the impact of non-\nPassage: Italy 9.8% Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: Table l: Posterior model estimates of percentage of total population infected as of 28th March 2020. Title: Estimating the number of infections and the impact of non-\nPassage: https://www.gazzettaufficiale.it/eli/id/2020/03/08/20A01522/sg .", "Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: R\u00e9union Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean . The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance , based on the surveillance system of mainland France . Influenza activity generally increases during austral winter, corresponding to summer in Europe . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Despite the distance of 9,300 km between R\u00e9union and France, the island is directly connected to Europe with four daily flights to France. These exchanges can impact respiratory pathogens circulation in southern and northern hemisphere. Results of this study can therefore be of interest to both Indian Ocean and Europe countries. Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Within a year, the E1-A226V mutation was present in La Reunion Island, and Ae. albopictus apparently vectored the large epidemic infecting 34% of La Reunion Island's population . All of the CHIKV strains isolated from Mayotte carried the E1-A226V mutation, and the mutation was also found in Madagascar in 2007 . The E1-A226V mutation was not present at the beginning of the Indian Ocean Islands outbreak . However, more than 90% of later viral strains found there had incorporated the mutation , indicating a genotype switch during the winter season . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: vector similar to the ones observed in Reunion Island .", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit", "Title: CDC Summary 21 MAR 2020,\nPassage: Healthcare workers caring for patients with COVID-19 are at elevated risk of exposure. Title: Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China\nPassage: Caring for 2019-nCoV patients represents a substantial exposure risk for ICU staff because of the following reasons: highly contagious with multiple transmission route, high exposure dose, long daily contact hours, and ICU stay. The basic reproductive number was estimated to be 2.2 , or as high as between 3.6 and 4.0 . The 2019-nCoV is proved to be transmitted by respiratory droplets, contact, and fecal-oral, even transmission through the eye is possible . The higher viral load and aerosol-generating procedures, such as noninvasive ventilation, magnify the exposure and transmission risk . Moreover, virus shedding can be prolonged and last for Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: Working in the ICU was also identifi ed as a risk factor for pandemic infl uenza; patients in ICU may be severely ill, with high viral loads, and staff may be heavily exposed during multiple aerosol-generating procedures. In addition, use of PPE and hand hygiene compliance may have been lower than in other wards or patients with pandemic infl uenza may have been unrecognized and therefore appropriate PPE not used. Title: CDC Summary 21 MAR 2020,\nPassage: Close contacts of persons with COVID-19 also are at elevated risk of exposure.", "Title: Temporal trends in the discovery of human viruses\nPassage: is therefore of considerable interest. Title: What\u2019s Past is Prologue: A Scoping Review of Recent Public Health and Global Health Informatics Literature\nPassage: the GHI team lead to identify themes and trends. Title: What\u2019s Past is Prologue: A Scoping Review of Recent Public Health and Global Health Informatics Literature", "Passage: Beginning in 2013, the PHI and GHI working groups within the American Medical Informatics Association have offered a 'Year in Review' session at the AMIA Annual Symposium. These sessions highlight advancements and trends in both the science and practice of PHI and GHI. This paper builds upon these Year in Review sessions by providing a semi-systematic review of the PHI and GHI literature over the past three years. Our goal is to summarize recent advancements and trends in both fields and suggest directions for future work that will further stimulate growth in the fields and advancements in the science of Title: What\u2019s Past is Prologue: A Scoping Review of Recent Public Health and Global Health Informatics Literature", "Passage: Finally, as we opened our search in 2014 to include all countries designated as LMICs according to the World Bank, we observed new topics surface in the literature. Specifically, we observed the presence of imaging informatics publications released in 2014 . These publications described the improvement of imaging services by integrating systems, reducing cost, using mobile devices, applying new imaging techniques in LMICs, and exploring new methods to identify and compare data in images . Reviewers also identified an additional theme related to emergency services supported by information systems in LMICs .", "Title: Understanding the genetics of neuropsychiatric disorders: the potential role of genomic regulatory blocks\nPassage: two additional recent datasets of SNPs associated with other neurodevelopmental phenotypes, i.e. autism spectrum disorder and bipolar disorder , were checked for overrepresentation in genomic regulatory blocks . BD-associated loci showed no significant difference from propensity of a random locus to fall in a genomic regulatory block, however, there was a marked increase in ASD-GWAS and SCZ-GWAS detected loci overlapping a genomic regulatory block, indicating a role of genes involved in developmental transcription factors and/or cell adhesion, cell-cell signalling, axon guidance genes in molecular mechanisms leading to autism and schizophrenia. It is worth noting here that, since the BD-GWAS study Title: Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015", "Passage: Autism spectrum disorder is a group of multifactorial neurodevelopmental conditions resulting in mental disability. Estimated prevalence of ASD in Arab countries varies widely between 1.4 and 29 per 10,000 children. Early diagnosis and intervention, can substantially improve outcome and reduce demands within the health care system. Several studies reported a significant genetic background, with a certain risk for heritability, and a 4:1 male to female ratio. Title: Understanding the genetics of neuropsychiatric disorders: the potential role of genomic regulatory blocks", "Passage: We applied the same approach to the recent GWAS for autism and bipolar disorder, two other neuropsychiatric disorders with high heritability . This analysis shows significant enrichment for the GWAS loci to overlap with GRBs in autism but not bipolar disorder . In autism 82 of the 180 loci overlap a GRB, and the GRB-based analysis indicates different gene targets than those originally assigned for 61 of these loci . Thus, the GRB method could help identify novel gene targets from the GWAS studies of a number of neuropsychiatric disorders, although potentially not for bipolar disorder. Title: Understanding the genetics of neuropsychiatric disorders: the potential role of genomic regulatory blocks", "Passage: and 80% by large population-based studies and meta-analysis of twin studies ; between 64% and 91% for autism by the most recent meta-analysis on twin studies and between 60% and 80% for bipolar disorders . On the other hand, the SNP-based heritability estimated on liability scale has been estimated between 23% and 32% for schizophrenia , 17% for autism and 25% for bipolar disorder . This missing heritability may come from variants with smaller effect sizes thus far missed due to the sheer population size needed to achieve statistical significance when testing for small effects , or other types of", "Title: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses\nPassage: The 1B human seasonal lineage within-and between-clade APDs are presented in Table 3 . For the most part, each clade had an APD of \u03fe7% from other clades and almost all had an APD of \u03fd7% within the clade. The within-clade exceptions were the 1B.1 and 1B.2 clades . The 1B.1 second-order clade had too few representative sequences to calculate genetic distance, and 1B.2 represented multiple monophyletic clades that individually did not meet our criteria for further division. Similarly, the extensive 1B.1.1 clade did not meet criteria for further splitting. The exception to the between-clade threshold was associated with clades Title: Molecular phylogenetics of the African horseshoe bats (Chiroptera: Rhinolophidae): expanded geographic and taxonomic sampling of the Afrotropics", "Passage: However, for the four clades whose mean PP in the four summed Partition Schemes fell below a threshold of 0.95, PS 3 and 4 had the most influence. The clades that were not delimited all had PP \u2264 0.95 but \u22650.90 and thus had marginal support. Most of the unsupported clades had short branches and weak node support in the species tree analysis . Distinguishing robustly defined lineages by congruence across all Prior Schemes, 19 evolutionarily independent lineages are delimited including all six lineages analyzed in the capensis group and the newly sequenced R. cf. denti/ simulator; and finally 8 Title: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses", "Passage: \"\u2426-2 H1\" viruses . We defined two third-order 1B. The 1B.2 clade contained two third-order clades that corresponded to previously described \"\u2426-2 H1\" and \"\u2426-1 H1\" clades. Based on average pairwise distances, and a large number of viruses, the third-order 1B.2.2 clade met the criteria for further subdivision into 1B.2.2.1 and 1B.2.2.2 . In addition to these named subdivisions, the 1B.2 clade from 2010 to the present contained sporadic human-to-swine transmission episodes in Argentina, Chile , China, Mexico, and Vietnam; these spillovers did not warrant the designation of a clade either due to failure to establish in swine populations or Title: Revalidation and genetic characterization of new members of Group C (Orthobunyavirus genus, Peribunyaviridae family) isolated in the Americas", "Passage: To better understand the genetic relationships among group C viruses, we conducted the ML trees based on the complete coding sequences in nucleotide and amino acids level for all segments . These viruses were clustered in a unique monophyletic clade with different topologies for each segment. The S and L segments present two major clades, namely of clade A and B . The clade A was subdivided in three: subclade Ia, composed by MURV, ORIV, and Restan ; subclade IIa, with MTBV and APEUV; subclade IIIa comprised by NEPV, Gumbo Limbo . The clade B was split into two subclades:", "Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections\nPassage: By prospective design, we mean that respondents are informed in advance of the day that they are requested to record their contacts. 6, 17, 32 In a retrospective design, respondents recall their contacts over a past time period without prior warning or instruction that they would be requested to do so. Of 64 surveys, 29 used a retrospective design and 26 used a prospective design. Only four surveys 6%) used both designs for the purpose of comparison. 10, 17, 50 For five surveys , it was not completely clear whether the study was prospective or retrospective. 20, 24, 30, 48 Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: The prospective design is subject to less recall bias than the retrospective design. This notion can be partly explained by the fact that respondents in the former are informed in advance about which days they will be assigned for reporting their contact information. Furthermore, they are also asked to keep a diary with them and finish reporting before the surveying day is elapsed. Thus, the prospective design requires more commitment from respondents. In return, a prospective design can obtain more reported contacts compared with retrospective design. 17, 50 However, large-scale studies are needed to further confirm these conclusions. Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: eFigure 4; http:// links.lww.com/EDE/B552 displays the trend of using study designs in social contact surveys over time, revealing that the retrospective design was more favored by researchers, except in the period 2005-2009 in which eight prospective surveys were implemented. 6,32 Title: Retrospective diagnosis of a famous historical figure: ontological, epistemic, and ethical considerations", "Passage: their agreement can serve as the support. It is an old-fashioned way to \"confirm\" a diagnosis when there is no evidence to rely on, but it is still one form of Bayesian decision-making because the change of plausibility from Pre-odds to Post-odds by increasing or decreasing the Likelihood Ratio is considered a confirmation or disconfirmation of the diagnosis. I suggest that retrospective diagnosis be evaluated in similar peer-review methods. Currently peer review medical journals seem to do this job in terms of the soundness of diagnostic reasoning. Unfortunately, however, the review does not seem as rigorous as for contemporary case", "Title: Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity\nPassage: successful treatment for HCV serves to circumvent the viral inhibition of IFN induction. Thus, HCV may be an example of a medically relevant persistent viral infection that persists due, in part, to loss of innate immune function. Persistence of other continuously replicating RNA viruses, such as chikungunya, measles, polyomavirus, may be similarly due to ineffective innate responses. Title: Type I Interferon Response Is Delayed in Human Astrovirus Infections", "Passage: Results suggest that HAstV infection is not able to disrupt the innate immune sensing pathway induced by polyI:C . Only a previous infection with RV was able to reduce by 60% the IFN-\u03b2 mRNA levels produced after polyI:C transfection, although differences were not statistically significant . HAstV and RV yields were similar between mock-transfected wells and wells transfected with polyI:C . As expected, antiviral activity in the supernatant of cultures at 32 hpi could only be detected in cells transfected with polyI:C, and the response could only be reduced by the presence of rotavirus infection . Title: UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection", "Passage: 4-fold fewer PDCA-1+ pDCs expressing intracellular IFN-a at 40 h, and 3-fold fewer at 48 h post-infection, in 3d mice as compared to WT . This trend was also reflected in the proportion of PDCA-1+ IFN-a+ pDCs at 40 h and 48 h after infection in 3d mice compared with WT . Title: Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection", "Passage: HuNV infection and disease is rapid, with symptoms developing within 24-48 hours of infection and lasting for a few days. Thus, we selected three days after challenge as a readout for infection in our studies, since relevant vaccine-generated immune responses would have to act very early after challenge. Lack of any of the three components of the adaptive response: B cells, CD4 T cells, or CD8 T cells significantly diminished vaccine effects generated by either live virus or VP1 capsid protein immunization, and delayed viral clearance during primary infection. This indicates that VP1 has antibody epitopes as well as MHC", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 isolated from some clustered cases . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization European Region . Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Abstract: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters\u2019 index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: Antibody arrays for simultaneous multiple antigen quantification are considered the most accurate methods . Liew validated one multiplex ELISA for the detection of 9 antigens; Anderson used microarray ELISA for multiplex detection of antibodies to tumor antigens in breast cancer, and demonstrated that ELISA-based array assays had the broadest dynamic range and lowest sample volume requirements compared with the other assays. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: for printing than for coating ELISA plates. Coating of a single well in microtiter plate requires 100 \u03bcl of a 1 \u03bcg/ml antibody solution, which is equivalent to 100 ng of IgG. For the ELISA-array, only 30 nl of a 50 \u03bcg/ml antibody solution is required for each spot, which is equivalent to 1.5 ng of IgG. With the characteristics of ease of use, sensitivity, specificity, and accuracy, the ELISA-array assay would be widely accepted for clinical use. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: antibodies demonstrated that 0.05 mg/ml was also suitable. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Antigen binding was performed in PBS at 37\u00b0C for 2 h, followed by washing 3 times. Incubation of ELISA plates with biotinylated detecting antibody cocktails was performed in PBS at 37\u00b0C for 2 h. After washing, specific binding of the detecting antibodies was reported by streptavidin-HRP and stained with Super Signal ELISA Femto Maximum sensitive substrate . Visualization of the plate was performed in AE 1000 cool CCD image analyzer. The signal intensity and background of each spot was read out and recorded with \"Monster\"software. The positive signals were defined as a signal value > 400 and a signal value", "Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: The diameter of hantavirus particles is 80-US210 nm, and the structure is spherical or ovoid. They are composed of 20-30% fat, >50% protein, 7% carbohydrates, and 2% RNA. They are very stable and can survive for more than 18 days at 4 \u2022 C and \u221220 \u2022 C and 10 days at room temperature . The genome comprises three negative sense, single-stranded RNAs that consist the small , medium , and large segments that encode the nucleoprotein , envelope glycoproteins , and viral RNA-dependent RNA polymerase , respectively . The outer membrane of hantavirus is composed of Gn and Gc Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: glycoprotein, which mediates the recognition of and entry into host cells. The crystal structure of HTNV Gn is very similar to that of PUUV Gn, which confirms that hantavirus Gn is conserved in hantavirus . Title: Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France", "Passage: negative polarity: S segment codes for the nucleocapsid protein and a small non-structural s protein in several viral species; M segment for the glycoprotein precursor of the envelope glycoproteins Gn and Gc; and L segment for the RNA-dependent RNA polymerase . Each hantavirus is predominantly associated with one or a few distinct mammal species and this stable virus-host association underscore the importance of host-related factors for understanding current distribution, evolution and epidemiology and mechanisms of emergence. Title: Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/K(b) Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: Hantaan virus antigens in the supernatants of the tissue samples of Tg mice were detected by sandwich ELISA. The anti-HTNV NP mAb 1A8 was prepared in the Department of Microbiology of our university. The mAb 1A8 was used as the coating antibody, and the horseradish peroxidase-conjugated mAb 1A8 was used as the detecting antibody . The supernatants of normal tissue were used as negative controls. First, add 100 \u00b5L prepared supernatants to duplicate wells and incubate for 2 h at 37\u00b0C. Next, remove the supernatants and wash three times. Then, add 100 \u00b5L detecting antibody to each well and incubate", "Title: Estimating the number of infections and the impact of non-\nPassage: countries between 7 and 43 million individuals have been infected with SARS-CoV-Z up to 28th March, Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: According to the situation report published by the WHO on 28 January 2020 , a total of 2798 confirmed 2019-nCoV cases have been reported globally; of these, 2761 cases were from China, including Hong Kong , Macau and Taipei . Thirty-seven confirmed cases have been reported outside of China in eleven countries in Europe, North America, Australia and Asia; of these 37 exported cases, 36 had a travel history from China or an epidemiological link to a case from China. Of the confirmed cases in China, 461 have been reported as severely ill, with 80 deaths to date. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: SARS-CoV and MERS-CoV cause severe disease, but despite the initial R0 estimations of greater than 2.0 for SARS-CoV , and some large outbreaks, neither were as transmissible as initial concerns suggested. SARS-CoV caused 8098 reported cases and 774 deaths in 37 countries before the epidemic was controlled. Control was thought to have been possible because a high proportion of cases were severe, making it easier to rapidly identify and isolate infected individuals. In addition, the virus was present at lower levels in upper airway secretions. There was no secondary transmission in the United States from the 8 imported cases, although Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: in Toronto, Canada, a single importation is thought to have led to about 400 cases and 44 deaths. Later estimates of R0 were less than 1, indicating that SARS-CoV may not have been capable of sustained transmission, especially in the setting of control measures.4", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: The analysis of the focus group data was undertaken by a single researcher who was neither present at the focus groups nor had read any preliminary findings. This work was verified by the focus group facilitators to ensure that any \"contextual richness\" had not been missed in the data. Thematic analysis was used to identify themes and concepts across the entire data set to \"identify repeated patterns of meaning\" . The process involved working through the six phases of thematic analyses as identified by Braun and Clarke . Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The study was part of a rapid response initiative; therefore focus groups were selected as the most efficient means of data collection in the time available. Eight semi-structured focus groups were recruited between May and July 2010 comprising 7 to 13 participants each and lasting approximately 1 hour. Separate focus groups were conducted for each of the target groups with a total of 80 participants representative of five target populations groups identified in consultation with Ministry of Health staff: M\u0101ori, Pacific Peoples, children , general population, and vulnerable people with chronic conditions (defined as those who are eligible for subsidised Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: All focus group sessions were recorded and independently, professionally transcribed. Transcriptions were mainly verbatim, with verbal padding and hesitations omitted. Apart from the facilitators, specific individuals were not identified in the transcripts or any subsequent reports. The extracts used to illustrate the content of each theme are identified by codes which correspond to the focus group transcripts from which they were taken .", "Title: Patterns of Positive Selection in Six Mammalian Genomes\nPassage: Since it first became possible to compare the sequences of complete mammalian genomes about five years ago, a number of genome-wide scans for positively selected genes have been conducted using phylogenetic methods . These studies have provided a valuable initial assessement of the genome-wide landscape of positive selection in mammals, but they have left many important questions unanswered. The analysis presented here, by incorporating non-primate mammalian genomes into a genome-wide scan for positive selection, represents a significant step forward. The larger, more divergent group of species improves power significantly, and the use of a nontrivial phylogeny provides insight into the Title: Patterns of Positive Selection in Six Mammalian Genomes", "Passage: particular patterns of positive selection that have helped to shape present-day genes. To our knowledge this is the largest and most detailed genome-wide analysis of positive selection to date, not only in mammals but in any group of organisms ). Title: Patterns of Positive Selection in Six Mammalian Genomes\nPassage: To accurately identify orthologous sequences in the six mammalian species, we used syntenic whole-genome alignments produced by the MULTIZ program on the following assemblies available through the UCSC genome browser : human , chimpanzee , macaque , mouse , rat , and dog . The human genome was used as a reference genome. We used the pairwise syntenic nets with respect to human genome as an input to MULTIZ pipeline to reduce the likelihood of paralogous alignments. We compensated for low sequence quality in some regions by masking the bases in chimpanzee, macaque, rat, and dog with sequence quality lower Title: Patterns of Positive Selection in Six Mammalian Genomes", "Passage: For each gene cluster we have selected the transcript that has been successfully mapped to the largest number of species, using CDS length as a secondary criteria. This procedure resulted in 17,500 genes that were successfully mapped to at least two additional species besides human. For technical reasons, we have removed 11 additional transcripts, obtaining orthologous multiple alignments for 17,489 genes, with average of \u223c4 non-human orthologs per gene. The number of genes in this data set for each species is shown in Table 1 .", "Title: Severe Measles Infection: The Spectrum of Disease in 36 Critically Ill Adult Patients\nPassage: Acute respiratory distress syndrome was defined in compliance with the Berlin conference on ARDS. 69 Adjunctive therapies of ARDS including prone positioning, inhaled nitric oxide , and extracorporeal circulation membrane oxygenation were recorded. Title: Severe imported malaria in an intensive care unit: a review of 59 cases", "Passage: frequent in those who died. These data are in agreement with literature review, where the fatality rate is higher in cerebral malaria and acute respiratory distress syndrome . Two of the patients were put on ECMO, used as a rescue therapy . They had been working in Angola and Mozambique for some years, had parasitaemia 2% and 3% respectively and severe ARDS and multiorganic dysfunction. One of them survived and recovered without respiratory sequelae, the other died in refractory shock. These cases show the importance of a clinical surveillance of all patients, because the evolution is sometimes unfavourable in cases Title: Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study", "Passage: Almost all patients had ARDS, categorized as severe in 86% , with 17% of them requiring ECMO. ICU and hospital mortality rates were 45% and 51% , respectively. Patients with aMDA-5 dermato-pulmonary syndrome had a higher ICU mortality than those with AS syndrome . Among the 26 ICU survivors, 5 were diagnosed with a cancer during the 279 days post-ICU stay follow-up. Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: Conclusions: Although MSF is generally considered a benign disease we had a high ICU admission rate and a considerable mortality rate. We found that the SAPS II score, the leukocytes count and aPTT are predictors of death in patients with MSF admitted to the ICU. Introduction: The Middle East Respiratory Syndrome coronavirus has caused several hospital outbreaks and frequently leads to severe critical illness. To learn from our experience, we described the response of our intensive care unit to a MERS-CoV hospital outbreak. Methods: This observational study was conducted at a 1000-bed tertiary-care hospital in Riyadh, Saudi Arabia which had", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Testing models of pathogenesis can be done more effectively when there is an animal model that mimics key aspects of the disease. There is no such model that closely mimics HFRS, but animal models exist for both the asymptomatic carriage of PUUV and SNV by their native carrier rodents, the bank vole Myodes glareolus and the deer mouse P. maniculatus; as well as a Syrian hamster model using ANDV or the related Maporal virus from Venezuela, for which an HCPS-mimetic disease is observed . Title: The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus", "Passage: virological examination of the trachea, lung, brain, heart, liver, spleen, kidney, stomach, intestine, and olfactory bulb. All nine animals were observed for clinical signs and weighed daily as an indicator of disease. Nasal and throat swabs were collected on 1, 3, 5, 7, 9 d.p.i. and transferred to 1 ml of phosphate buffer solution . Virus titers were determined by end-point titration in MDCK cells. Title: Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France", "Passage: between the reservoir and the disease is not clearly elucidated . Among likely explanations, it could be that many NE cases remain undetected or misdiagnosed due to mild symptoms which possibly lead to confusion with other diseases and to a lack of clinician awareness for hantavirus diseases in non-endemic areas. Alternatively, bank voles could be free of PUUV infections in specific areas or PUUV strains that circulate in these areas would be not transmitted to or infectious for humans or provoke a milder infection. Title: The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus\nPassage: the trachea, lung, brain, heart, liver, spleen, kidney, stomach, intestine, and olfactory bulb. All nine animals were observed for clinical signs and weighed daily as an indicator of disease. Nasal and throat swabs were collected on 1, 3, 5, 7, 9 d.p.i. and transferred to 1 ml of phosphate buffer solution . Virus titers were determined by end-point titration in MDCK cells.", "Title: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses\nPassage: Clade designations for 1A swine lineage. The 1A lineage contained 1,889 viruses from 34 countries collected from 2010 to the present . According to our nomenclature rules, we refined the classification of 1A viruses into three second-order divisions, each of which corresponds to earlier, regional classifica- Table 2 . Each clade had an APD of \u03fe7% from other clades and an APD of \u03fd7% within the clade, although some minor exceptions were made when all other clade-defining criteria were met and mitigating circumstances supported the exception. Within-clade exceptions were made for the first-order 1A.1 and the extensive 1A.1.1 second-order clade Title: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses", "Passage: Clade designations for 1C swine lineage. The 1C lineage consisted of 315 viruses from 14 countries collected from 2010 to the present in China and South Korea. Avian H1 HA sequences were generally restricted to two monophyletic clades distinct from, but sister to, the 1C swine viruses: these HA sequences were defined as \"Other-Avian.\" The within-and between-clade APDs are presented in Table 4 . For the most part, each clade had an APD of \u03fe7% from other clades and an APD of \u03fd7% within the clade. The one within-clade exception in this lineage was 1C.2 , which had multiple monophyletic Title: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses", "Passage: The 1B human seasonal lineage within-and between-clade APDs are presented in Table 3 . For the most part, each clade had an APD of \u03fe7% from other clades and almost all had an APD of \u03fd7% within the clade. The within-clade exceptions were the 1B.1 and 1B.2 clades . The 1B.1 second-order clade had too few representative sequences to calculate genetic distance, and 1B.2 represented multiple monophyletic clades that individually did not meet our criteria for further division. Similarly, the extensive 1B.1.1 clade did not meet criteria for further splitting. The exception to the between-clade threshold was associated with clades Title: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses", "Passage: were placed into seven clades. The numerically dominant clades reflected intensive surveillance in the United States , investigator sequencing efforts in Canada , and the rapid dissemination of the 2009 H1N1 pandemic virus across global swine populations . Similarly, coordinated surveillance in Europe and Asia captured two primary clades of 1C Eurasian avian lineage currently circulating in the two continents.", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: Bats have a suite of antiviral defenses that keep the amount of virus in check. For example, some bats have an antiviral immune response called the interferon pathway perpetually switched on. In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm, include the loss of certain genes that normally promote inflammation. However, no one has previously explored how these unique antiviral defenses of bats impact the viruses themselves. Now, Brook et al. have studied this exact question using bat cells grown in the laboratory. Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: The experiments made use of cells from one bat species -the black flying fox -in which the interferon pathway is always on, and another -the Egyptian fruit bat -in which this pathway is only activated during an infection. The bat cells were infected with three different viruses, and then Brook et al. observed how the interferon pathway helped keep the infections in check, before creating a computer model of this response. The experiments and model helped reveal that the bats' defenses may have a potential downside for other animals, including humans. In both bat species, the strongest antiviral responses were Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: Recent research advances are beginning to shed light on the molecular mechanisms by which bats avoid pathology from these otherwise virulent pathogens . Bats leverage a suite of species-specific mechanisms to limit viral load, which include host receptor sequence incompatibilities for some bat-virus combinations and constitutive expression of the antiviral cytokine, IFN-a, for others . Typically, the presence of viral RNA or DNA in the cytoplasm of mammalian cells will induce secretion of type I interferon proteins , which promote expression and translation of interferon-stimulated genes in neighboring cells and render them effectively antiviral . In some bat cells, the Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: countered by the virus spreading more quickly from cell to cell. This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures like humans are not.", "Title: Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors\nPassage: Cysteine-protease inhibitors have gained considerable attention over the last couple of decades and many classes of compounds are currently in human clinical trials for a number of diseases. Interest in papain family cysteine proteases as chemotherapeutic targets is derived from the recognition that they are critical to the life cycle or pathogenicity of many microorganisms. The cysteine proteases from Streptococcus sp. , Staphylococcus sp. , Plasmodium falciparum and Trypanosoma cruzi are some of the most widely studied members of papain family which have been reported to be linked with severity of infection and various pathological conditions caused by these microorganisms. Title: Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors", "Passage: In summary, the results of the present study have established that 1-substituted pyridylimidazopyridine derivatives could be candidate for novel and potent inhibitors of papain like cysteine proteases, which play deleterious role in the progression of different diseases caused by diverse microorganisms. Therefore, this group of compounds could be the subject of future research to confront the challenges with resistant microorganisms that is a major threat globally. Title: Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors", "Passage: In summary, the results of the present study have established that 1-substituted pyridylimidazopyridine derivatives could be candidate for novel and potent inhibitors of papain like cysteine proteases, which play deleterious role in the progression of different diseases caused by diverse microorganisms. Therefore, this group of compounds could be the subject of future research to confront the challenges with resistant microorganisms that is a major threat globally. Title: Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors", "Passage: Text: Cysteine-protease inhibitors have gained considerable attention over the last couple of decades and many classes of compounds are currently in human clinical trials for a number of diseases. Interest in papain family cysteine proteases as chemotherapeutic targets is derived from the recognition that they are critical to the life cycle or pathogenicity of many microorganisms. The cysteine proteases from Streptococcus sp. , Staphylococcus sp. , Plasmodium falciparum and Trypanosoma cruzi are some of the most widely studied members of papain family which have been reported to be linked with severity of infection and various pathological conditions caused by these", "Title: Rapid RNA Exchange in Aqueous Two-Phase System and Coacervate Droplets\nPassage: the corners with Valap, and evaporation was allowed to occur through the edges over several hours. Slides were observed either with a confocal microscope or with a Nikon TE2000 inverted fluorescence microscope with a 100\u00d7 oil objective. Title: Rapid RNA Exchange in Aqueous Two-Phase System and Coacervate Droplets\nPassage: to be: Title: Rapid RNA Exchange in Aqueous Two-Phase System and Coacervate Droplets", "Passage: to be: Title: Rapid RNA Exchange in Aqueous Two-Phase System and Coacervate Droplets\nPassage: coacervate samples with 5 \u00b5M 5\u2032-6-FAM-labeled RNA 15-mer at room temperature in 100 mM Tris-Cl pH 8. On the left, the system clearly separates into two phases with the RNA in the bottom, complex-enriched phase. On the right, the system is composed of small, dispersed complex-enriched droplets in bulk aqueous solution and resulted in a turbid solution. At increasing salt concentrations, the charge interactions between the pLys and ATP are disrupted and the system starts to tend towards a one-phase system again. . Scale bars are each 100 \u00b5m. Title: Rapid RNA Exchange in Aqueous Two-Phase System and Coacervate Droplets\nPassage: All imaging visualization, analysis, calculations, and production of movies were performed using FIJI . All curve fitting was performed using MATLAB . All figures were produced using Adobe Illustrator .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: cases of acute febrile disease with renal compromise were described from several Eurasian countries and Japan, often in association with military engagements . HFRS as a distinct syndrome, however, was first brought to the attention of western medicine in association with an outbreak that occurred among United Nations troops during the Korean conflict between 1951 and 1954, where more than 3,200 soldiers were afflicted . It took more than two decades until the etiologic agent, Hantaan virus , was isolated from the striped field mouse Apodemus agrarius, detected in part by the binding of antibodies from patient serum samples to Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: The initiation of careful observation and prompt but judicious supportive treatment is crucial to improve patient survival condition for both HFRS and HCPS . It has been demonstrated that admission to the ICU and supportive treatment could greatly reduce the mortality rate of HFRS . In general, the treatment principle for HFRS patients is using intravenous hydration and electrolyte therapy to maintain physiological blood pressure. Platelet transfusions can be applied to reduce the mortality in patients with severe thrombocytopenia. Intermittent hemodialysis is the first choice to improve uremia condition and rectify kidney dysfunction in patients with acute kidney injury. Continuous Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: It is wildly accepted that HFRS and HCPS are caused by uncontrolled systemic inflammatory responses, in which multiple inflammatory cytokines, especially TNF-\u03b1, IL-8, and RANTES, contributed to disease progression ; however, immunoregulation treatment in HFRS or HCPS is undesirable. A recent study with depletion of alveolar macrophages, which are considered the main resource for proinflammatory responses, could not prevent ANDV-caused pathogenesis in hamsters . The immunomodulatory treatment of corticoids was firstly performed during the Korean war, but the case fatality rate was not improved . In Chile, a retrospective analysis suggested that a high dose of methylprednisolone could reduce mortality Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: in 22 HCPS patients . However, a double-blind clinical trial in Chile failed to observe a significantly improved outcome between methylprednisolone recipients and placebo recipients for HCPS. Similarly, another randomized prospective study did not show any benefit from corticosteroid treatment in HFRS patients .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Phage display technology has facilitated the production of protein libraries, which are formed with large numbers of phage particles displaying different molecules . Specific binder screening with biopanning allows the enrichment of the desired molecule . The first step is the incubation of the display library with an immobilized surface of the entire cell. The non-binding phages are then removed by extensive washing and the binders are eluted by acid or salt buffer. Then, binders are amplified using an appropriate bacterial host cell such as E. coli. To obtain highaffinity targets, up to five rounds of biopanning are performed . Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: In the mid-1980s, the principle of modifying the filamentous phage genome to display polypeptides as fusions to coat proteins on the virion surface was invented by Smith and colleagues . Based on the ideas described in Parmley and Smith , groups in California, Germany, and the UK developed phage-display platforms to create and screen libraries of peptide and folded-protein variants . This technology allowed, for the first time, the ability to seamlessly connect genetic information with protein function for a large number of protein variants simultaneously, and has been widely and productively exploited in studies of proteinprotein interactions. Many excellent", "Title: 1918 Influenza: the Mother of All Pandemics\nPassage: 12. Reid AH, Fanning TG, Hultin JV, Taubenberger JK. Origin and evolution of the 1918 \u201cSpanish\u201d influenza virus hemagglutinin gene. Title: The 1918 Influenza Pandemic: Looking Back, Looking Forward\nPassage: finding, and it will be important for future work to reconcile the well-accepted idea that a 1918-like virus may have circulated in Europe and North America in the second half of the 19th century, with the notion that Madrid would have escaped this virus. Title: 1918 Influenza: the Mother of All Pandemics\nPassage: by the Same Virus? If So, How and Why? Title: 1918 Influenza: the Mother of All Pandemics\nPassage: Could a 1918-like Pandemic Appear Again?", "Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection\nPassage: \"An acute respiratory illness with a measured temperature of \u2265 38 \u00b0C and cough, with onset within the past 10 days\". a Compared with corresponding definition published in 1999. 9 Box 2. Criteria previously used in regional definitions of severe acute respiratory infection Among individuals aged above five years, the criteria used were those for pneumonia in this age group, i.e. sudden onset of fever above 38\u00b0C, cough or sore throat, shortness of breath or difficulty breathing, and requiring hospitalization. Among individuals aged between two months and five years, the criteria used were either those for pneumonia in this age Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection", "Passage: viruses. For the detection of infections with influenza viruses in children younger than five years, it may be advisable to use a tailored case definition, e.g. one that uses a higher temperature cutoff for fever 28 or includes rhinorrhea or other additional respiratory symptoms 35 , to increase specificity. Title: Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection", "Passage: conducted before WHO's 2011 consultation, the most predictive symptoms of influenza were found to be cough, fatigue, fever and myalgia. 18, 19 As sore throat had been identified as a negative predictor of influenza 13, 17, 19 and been found hard to diagnose in young children, it was omitted from the clinical case definition of ILI proposed in 2011. 17 The criterion \"absence of another diagnosis\" was also omitted because its inclusion in the 1999 definition had resulted in the exclusion of ILI cases with underlying chronic conditions, e.g. asthma and congestive heart failure, that can influence influenza risk. The Title: Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance", "Passage: We found 323 persons 6-7%) who met the pneumonia case definition in the previous year. Almost all met the case definition with self-reported cough and difficulty breathing for at least two days; 2% reported only a physician's diagnosis of pneumonia; and 12% reported both. There were 60 cases of pneumonia reported among children <5 years old, and 263 cases among persons aged five years or older. Among the children <5 years old, 31 met the case definition for severe pneumonia.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: DCs, may be an occupational group with significantly higher incidence of seropositivity to MERS-CoV when animals have active MERS-CoV infections . Expanded virological investigations of African DCs may lead to more seropositive animals and geographic areas in which humans may be at risk. It is possible that there are areas where humans already harbour MERS-CoV infections that have not been identified because of an absence of laboratory surveillance. Virological investigations of bats may lead to findings of ancestral viruses and viral 'missing links' and identifying any other animal sources of zoonotic spread is important to inform options for reducing human Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: donors and 300 selfidentified animal workers from the Jazan Region of the KSA during 2012 . Similarly, a study of four herdsmen in contact with an infected DC herd in Al-Ahsa, eight people who had intermittent contact with the herd, 30 veterinary surgeons and support staff who were not exposed to the herd, three unprotected abattoir workers in Al-Ahsa and 146 controls who were not exposed to DCs in any professional role, found none with serological evidence of past MERS-CoV infection using the ppNT assay . A delay in the neutralizing antibody response to MERS-CoV infection was associated with increased Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: As a group, HCWs comprised 16 % of MERS cases in the KSA and South Korea. It is apparent that the weekly proportion of infected HCWs increases alongside each steep rise in overall detections . In May 2013, the WHO published guidelines for IPC during care of probable or confirmed cases of MERS-CoV infection in a healthcare setting . This is explainable because to date, each case rise has been intimately associated with healthcare-facility related outbreaks . These rises in MERS-CoV detections can decrease the average age during each event because HCWs are usually younger than inpatients with MERS. Healthcare", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: consideration for human influenza vaccination. Title: Virus-Vectored Influenza Virus Vaccines\nPassage: current limitations of influenza vaccines. Title: Virus-Vectored Influenza Virus Vaccines\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147686/ Title: Virus-Vectored Influenza Virus Vaccines\nPassage: approaches.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: phage populations in tandem with the relative abundance of free-living heterotrophic bacteria . Environmental metagenomics efforts are just beginning to unravel the composition of viral ecosystems. The existing data suggest that filamentous phage comprise minor constituents of viral communities in freshwater and reclaimed and potable water but have much higher frequencies in wastewater and sewage , with the caveat that biases inherent to the methodologies for ascertaining these data have not been not well validated. There are no data describing the population dynamics of filamentous phage and their host species in the natural environment. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: phage populations in tandem with the relative abundance of free-living heterotrophic bacteria . Environmental metagenomics efforts are just beginning to unravel the composition of viral ecosystems. The existing data suggest that filamentous phage comprise minor constituents of viral communities in freshwater and reclaimed and potable water but have much higher frequencies in wastewater and sewage , with the caveat that biases inherent to the methodologies for ascertaining these data have not been not well validated. There are no data describing the population dynamics of filamentous phage and their host species in the natural environment. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: effects upon their bacterial hosts that may not result in the development of resistance to infection. Several studies have reported increased antibiotic sensitivity in bacterial populations simultaneously infected with either wild type filamentous phage or phage engineered to repress the cellular SOS response . Filamentous phage f1 infection inhibited early stage, but not mature, biofilm formation in E. coli . Thus, unmodified filamentous phage may be of future interest as elements of combination therapeutics against certain drug-resistant infections. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: effects upon their bacterial hosts that may not result in the development of resistance to infection. Several studies have reported increased antibiotic sensitivity in bacterial populations simultaneously infected with either wild type filamentous phage or phage engineered to repress the cellular SOS response . Filamentous phage f1 infection inhibited early stage, but not mature, biofilm formation in E. coli . Thus, unmodified filamentous phage may be of future interest as elements of combination therapeutics against certain drug-resistant infections.", "Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: ere is no specific treatment for MERS-CoV. Like most viral infections, the treatment options are supportive and symptomatic . At present, no vaccine exists for preventing the infections of MERS-CoV. e CDC indicated that preventative actions should be taken for any type of respiratory illness . Such actions include washing hands with water and soap for around 20 seconds or using hand sanitizers with alcohol if no water is available. One must cover their nose and mouth during instances of sneezing and coughing with a tissue and avoid touching the mouth, nose, or eyes with their hands until washed properly. Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: Various therapeutic options have been investigated for the treatment of MERS-CoV, but no therapy of proven value currently exists. The use of SC was associated with adverse outcome in SARS 69 and is not recommended for MERS-CoV. Many agents have shown inhibitory effects against MERS-CoV in cell culture including interferon +/\u00c0 ribavirin, cyclosporine A, mycophenolic acid, chloroquine and lopinavir. 70 Interferons, lopinavir, mycophenolate, possibly alisporivir and combinations are reasonable choices for testing in controlled clinical trials. Exploratory post hoc metaanalysis of studies related to SARS and severe influenza has shown a significant reduction in mortality following convalescent plasma treatment compared Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: Supportive care with appropriate infection control is the mainstay of current CDC treatment guidelines for 2019-nCoV. There are not yet any approved antiviral treatments for 2019-nCoV. Emergency Use Authorizations for compassionate use cases may be forthcoming from the US federal government for normally unapproved treatments. Supportive treatment predominantly includes respiratory support, hydration, and antipyretics. General treatment for severe cases should focus on the preservation of vital organ function. In the future, antiviral medications may be available. If a secondary bacterial infection such as pneumonia develops, targeted antibiotics are indicated. Title: Host resilience to emerging coronaviruses", "Passage: The current treatment and prevention options for SARS-CoV and MERS-CoV are limited. So far there are no licensed vaccines for SAR-CoV or MERS-CoV, although several strategies have been tried in animal models . There are also no antiviral strategies that are clearly effective in controlled trials. During outbreaks several antiviral strategies were empirically tried, but these uncontrolled studies gave mixed results . The main antivirals used were ribavirin, lopinavir and ritonavir . These were often used in combination with IFN therapy . However, retrospective analysis of these data has not led to clear conclusions of the efficacy of these treatment", "Title: Current and Novel Approaches in Influenza Management\nPassage: LAIV viruses in the nasopharynx elicit immune response that epitomizes a natural influenza infection. For this reason, LAIV has shown some superiority over the IIV in terms of the induction of mucosal immunity via secreted immunoglobulin A . Use of the LAIV has proven to be safe in children and immunocompromised persons . The most spelt-out advantage is the \"non-invasive\" capacity of the attenuated viruses and this had made it suitable to use for all categories of vaccines, although LAIVs are not recommended for people with underlying chronic medical conditions . A typical setback to the use of the LAIV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: February and then manufacturers begin production, taking at least six months to produce the millions of vaccine doses required for the fall . If the prediction is imperfect, or if manufacturers have issues with vaccine production, vaccine efficacy or availability can be compromised . LAIV is not recommended for all populations; however, it is generally considered to be as effective as inactivated vaccines and may be more efficacious in children . While LAIV relies on antigenic match and the HA and NA antigens are replaced on the same schedule as the TIV , there is some suggestion that LAIV may Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: decade and it has been reported to protect young individuals better than IIV . Importantly, recent studies showed that LAIV can pre-sensitize the population and, subsequently, synergistically boost the efficacy of IIV . It should be noted that the use of LAIV in poultry requires strict safety standards due to concerns about the possibility that wild type strains may circulate in domestic poultry without apparent clinical symptoms, undergo genetic reassortment with the vaccine virus, and produce novel virulent strains . An ideal poultry LAIV should not be able to revert to wild type virus or undergo reassortment with field strains. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: in humans . Currently, NA-specific antibody responses are not considered a correlate of protection . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx . LAIV immunization induces serum antibody responses, mucosal antibody responses , and T cell responses. While robust serum antibody and nasal wash antibody responses are associated with protection from infection, other immune responses, such as", "Title: Estimating the number of infections and the impact of non-\nPassage: representing between 1.88% and 11.43% ofthe population. The proportion of the population infected Title: Estimating the number of infections and the impact of non-\nPassage: 03/0 25% 50% 753% 100% Title: Estimating the number of infections and the impact of non-\nPassage: Country % of total population infected Title: Quantifying social distancing arising from pandemic influenza\nPassage: The total population size of Sydney was NZ810 700, of which at least 14 130 were admitted to hospital and approximately 3500 died as a result of influenza infection . Based on a survey of 600 establishments covering 106 923 employees, the proportion of workers that were absent from duty as a result of influenza was 36.6% . This was considered as an unbiased estimate of the clinical attack rate, although we argue that the serological attack rate may have differed.", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Like SARS-CoV, 2019-nCoV induced pneumonia through respiratory tract by clinical observation. Therefore, the presence of viral antigen in oral swabs was used as detection standard for 2019-nCoV. Similarly, two times of oral swabs negative in a 24-h interval was considered as viral clearance by patients officially. Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: swabs were only taken when patients were symptomatic. Previously, virus isolation has been the gold standard for infl uenza detection but RT-PCR is now considered to be more sensitive and specifi c. A previous study by some of the current authors has shown that seroconversion occurs in 80%-90% of serum samples if they are tested a suffi cient time after infection . Nasal swabs are a relatively peripheral type of sample . If viral load is low in the nose, the sample may be insuffi cient as an antigenic stimulus to induce a detectable level of seroconversion in the serum. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: In the first investigation, we aimed to test whether viral positive can be found in anal swab and blood as well as oral swabs. We conducted a molecular investigation to patients in Wuhan pulmonary hospital, who were detected as oral swabs positive for 2019-nCoV upon admission. We collected blood, oral swabs and anal swabs for 2019-nCoV qPCR test using previously established method . Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: through routine surveillance, and thus pose a threat to other people. In contrast, we found viral antibodies in near all patients, indicating serology should be considered for 2019-nCoV epidemiology. A possible shift from oral positive during early infection to anal swab positive during late infection can be observed. This observation implied that we cannot discharge a patient purely based on oral swabs negative, who may still shed the virus by oral-fecal route. Above all, we strongly suggest using viral IgM and IgG serological test to confirm an infection, considering the unreliable results from oral swabs detection.", "Title: Advanced Molecular Surveillance of Hepatitis C Virus\nPassage: Hepatitis C virus infection is an important global public health problem. Approximately 180 million people are currently infected with HCV , and an alarming number of new infections occur annually . The prevalence of hepatitis C varies significantly worldwide, imposing an important burden in highly endemic countries . HCV infection is commonly associated with chronic liver disease, which frequently results in the advanced stages of cirrhosis and hepatocellular carcinoma following years of silent infection . Title: Development and Applications of VSV Vectors Based on Cell Tropism", "Passage: Hepatitis C virus has already infected more than 3% of the worldwide population and 80% of those infected develop persistent HCV infection . Persistent HCV infection often leads to chronic hepatitis, hepatic steatosis, cirrhosis, and hepatocellular carcinoma. Currently, there are still 1.5 million or more HCV carriers in Japan. Title: Interferon Lambda: Opportunities, Risks, and Uncertainties in the Fight Against HCV\nPassage: Hepatitis C virus is a positive sense, single-stranded RNA virus in the family Flaviviridae. It is estimated that as many as 160 million people are chronically infected worldwide with 3-4 million new infections every year . With a global prevalence of 2.35%, estimated to range between 0.14% on the island of Reunion and 14% in Egypt , there is a large economic cost and burden to society. Title: The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy", "Passage: Worldwide 92-149 million people, representing approximately 2% of the world's population, are chronically infected with HCV , one of the causative agents of viral hepatitis. HCV is a blood borne virus and transmission occurs parenterally, mainly by reusing injection material, insufficient sterilization of medical tools, or by transfusion of unscreened blood or blood products. As screening of blood products is a standard procedure nowadays in most countries, people who inject drugs have the highest risk of contracting hepatitis C. In fact, over 60% of injecting drug users are positive for HCVantibodies .", "Title: Self-Interest versus Group-Interest in Antiviral Control\nPassage: summarize the main findings. Title: Estimating the number of infections and the impact of non-\nPassage: main analysis. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: Characteristics of the 198 subjects are shown in Table 1 according to intervention arm. In general the groups were wellmatched. After randomization 70 of the households declined any home visits or could not be contacted after numerous repeated attempts. Proportionally more of these dropouts were in households where the index was a young adult, whereas there were few dropouts when the index subject was a child. Dropout was higher in households of index subjects who had a negative result on the rapid influenza test compared to those who had a positive result . Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: In terms of adherence, 45% of index subjects in the face mask arm reported wearing a mask often or always during the follow-up period, compared to 30% and 28% in the control and hand hygiene arms, respectively. The higher reported compliance in index subjects in the face mask group compared to household contacts was validated when at the final home visits the index subjects had used a median of 12 masks whereas household contacts had only used a median of 6 ; these include the mask worn and then disposed of by each individual as part of the demonstration and", "Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies\nPassage: a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: In summary the data presented here clearly demonstrate that KATNAL1 plays an important role in a variety of neuronal processes including neuronal migration, neuronal morphology and ependymal ciliary function. The downstream effect of these defects leads in turn to a number of behavioural changes including in learning and memory, reaction to anxiogenic situations and circadian rhythms. These data therefore highlight how perturbations in KATNAL1 may play a role in neuronal dysfunction and demonstrates that the enzyme is a novel candidate in the study of behavioural and neurodevelopmental disorders. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: In summary the data presented here clearly demonstrate that KATNAL1 plays an important role in a variety of neuronal processes including neuronal migration, neuronal morphology and ependymal ciliary function. The downstream effect of these defects leads in turn to a number of behavioural changes including in learning and memory, reaction to anxiogenic situations and circadian rhythms. These data therefore highlight how perturbations in KATNAL1 may play a role in neuronal dysfunction and demonstrates that the enzyme is a novel candidate in the study of behavioural and neurodevelopmental disorders. Title: A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies", "Passage: and ciliary function deficits suggesting KATNAL1 plays an essential role in these processes. These findings are the first to our knowledge to conclusively show that mutations in Katnal1 lead to behavioural and neuronal disturbances and provide insight regarding the clinical associations that have been linked to the gene. performed on mouse cohorts that were partially or completely congenic on the C57BL/6 J background.", "Title: The Trojan Chicken Study, Minnesota\nPassage: Statistical analysis was performed with SAS version 8.0 . Chi-squared analysis and Fisher exact test were used to compare categorical variables with powder contamination. We used t tests to compare continuous variables. Logistic regression modeling was attempted, but the models did not converge. Odds ratios and confidence intervals were calculated by using EpiInfo . Title: Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People\u2019s Republic of China\nPassage: the waves. Non-parametric tests, including the Wilcoxon and Kruskal Wallis tests were used to compare continuous variables such as age and time between illness onset and other dates of interest. Chi-square tests were used to compare frequencies of demographic and other categorical variables for the three waves. SPSS 17.0 was used for analyses. Title: A method of processing nasopharyngeal swabs to enable multiple testing", "Passage: For categorical data we used the Chi-square test to compare distributions. To compare mean values between groups we used paired t-test and analysis of variance . Title: Coinfection and Mortality in Pneumonia-Related Acute Respiratory Distress Syndrome Patients with Bronchoalveolar Lavage: A Prospective Observational Study\nPassage: Categorical variables were compared using the chi-square test or Fisher exact test. Descriptive variables were expressed as the mean AE standard deviation. All variables were tested for normal distributions by using the Kolmogorov-Smirnov test. The Student t test was used for comparing the means of continuous variables with a normal distribution and the Mann-Whitney U test was used for the remaining variables. The cumulative survival curves as a function of time were generated through the Kaplan-Meier approach and compared using the log-rank test. All the statistical tests were two tailed and P < 0.05 was considered statistically significant. The SPSS", "Title: Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies\nPassage: basis of the present study. Informed consent/parent assent was consistent with the Declaration of Helsinki. Phenotypes were defined by age of illness onset, clinical features, disease course, race or autoantibodies. Disease course was classified as monocyclic if the patient achieved remission without evidence of active disease, based on clinical examination and laboratory testing, within 2 years of diagnosis; as polycyclic if the patient had recurrence of active disease after a definite remission; as chronic continuous if disease activity persisted for >2 years; and as undefined if follow-up was <2 years from the time of diagnosis . Clinical, demographic and autoantibody Title: Relapsing macrophage activating syndrome in a 15-year-old girl with Still's disease: a case report", "Passage: Still's disease was described for the first time in children by George Still in 1896. It is characterized by a fever of approximately 39\u00b0C which continues for more than seven days, arthralgias or arthritis of two weeks duration or longer, and macular and/or maculopapular rash which is non-pruritic and salmon pink in color. Sore throat, lymph node swelling, hepatomegaly and/or splenomegaly with abnormal liver function studies, may also be present . Typically, laboratory studies show an elevated ESR, which is accompanied by leukocytosis with the predominance of granulocytes. Normocytic normochromic anemia with hemoglobin values less than 10 g/dl and reactive Title: Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies", "Passage: The juvenile idiopathic inflammatory myopathies are a heterogeneous group of acquired systemic autoimmune diseases characterized by symmetric proximal weakness, the presence of characteristic rashes and other systemic features. While the aetiology of these disorders remains unknown, many lines of evidence suggest that they result from the interaction of multiple genetic risk factors and environmental exposures . Title: Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies\nPassage: characteristics of the study population are described in Table 1 . Only the autoantibody phenotypes defined as anti-aminoacyl-tRNA synthetase, anti-signal recognition particle , anti-Mi2, anti-p155, anti-MJ, anti-U1 RNP and autoantibody negative were included in the analyses of environmental factors.", "Title: Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral Restrictions at the Plasma Membrane\nPassage: These unavoidable processes are common to all enveloped viruses. Moreover, the lipid envelope is the one component of the virus particle that is not encoded by the virus itself. It is perhaps unsurprising that the mammalian host has evolved multiple antiviral mechanisms whose role is to inhibit viral replicative processes that are associated with entry and exit , necessitating either the evolution of directly encoded countermeasures by the virus, or other mechanisms of resistance or avoidance. Furthermore, these mechanisms are often regulated by type 1 interferons and pattern recognition responses, linking these factors to the wider antiviral immune response. Title: The role of viral persistence in flavivirus biology", "Passage: When mammalian cell cultures are acutely infected with TBFV, a legion of general cellular defense and antiviral systems are triggered, as are specific factors designed to limit or restrict virus reproduction. Some of these include type I interferon , type III interferon , mitochondrial activated signaling, and the induction of inflammatory factors, such as interleukins . For example, the IFN-induced tripartite motif protein, TRIM79a, has been shown to restrict TBEV replication by degrading NS5 . The unimpeded deployment of these antiviral factors and systems would lead to cell death. Cell death is thought to be mediated primarily through apoptosis , Title: Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral Restrictions at the Plasma Membrane", "Passage: are also activated directly by pattern recognition responses . In addition to the activation of systemic innate and adaptive immunity, a number of these ISGs have direct antiviral activity against the replicative stages of diverse mammalian viruses . These antiviral factors, sometimes called restriction factors, often target common pathways or structures that are essential for viral replication, and which cannot be simply mutated around. In the case of lentiviruses, several restriction factors have been identified that are targets of virally encoded accessory proteins , for example tetherin and Vpu described below. The evolutionary arms race between these countermeasures and species-specific Title: Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral Restrictions at the Plasma Membrane", "Passage: may prevent the effective viral envelope clustering that is required particularly for IAV fusion and the IFITM multiplexes could also form a \"meshwork\" within the outer leaflet of the membrane that not only decreases fluidity and imposes rigidity but induces an outward membrane curvature that opposes the forces exerted by the viral fusion machinery. These general mechanisms may account for the diversity of viruses inhibited, including nonenveloped viruses, such as reoviruses, that do not require fusion, but do need to disrupt the endosomal membrane to enter the cell . Such models are also consistent with observations of IAV and Semliki", "Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016\nPassage: 68.8 % males: mean age was 53.2 years , and 31.2 % females: mean age was 53.2 years , where the youngest patient reported was 10 month and the oldest patient reported was 109 year old. Comorbidities were reported in 46.9 %: mean age was 60.1 and 71.8 % male and 28.2 % female. Healthcare workers were reported to be 15.6 %, mean age was 38.6 and 53.3 % male, 46.7 % female and 19.7 % of them had comorbidities. 12.1 % reported with history of camel contact; mean age was 56.7 and 91.7 % male, 8.3 % female and Title: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey", "Passage: Among our cohort of 215 children, 57% were male. The median age of the patients was 31 months , with 19% of the children having less than 3 months of age . As shown in Table 1 , 101/215 children presented with one or more underlying co-morbid condition, principally chronic lung diseases and neurological disorders. The median age of patients presenting co-morbidities was significantly higher than of those without . Title: Clinical profile and outcome of patients with acute kidney injury requiring dialysis\u2014an experience from a haemodialysis unit in a developing country", "Passage: The mean age of patients was 36.7 \u00b1 14.5 years, with more than two third being in the age group between 21 to 40 years. Gender distribution was nearly equal, with 50.3 % being male. Patients came from all corners of the country with more than a third coming from the capital Addis Ababa and two third were urban residents . The majority of patients acquired AKI in the community. Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years .", "Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers\nPassage: Text: The virus family Arenaviridae consists of only one genus, but most viruses within this genus can be divided into two different groups: the Old World arenaviruses and the New World arenaviruses . The differences between the two groups have been established through the use of serological assays. Most of the arenaviruses cause persistent infection in rodents without any symptoms, and humans acquire a variety of diseases when zoonotically infected. Lymphocytic choriomeningitis virus is the only arenavirus to exhibit a worldwide distribution, and causes illnesses such as meningitis . Congenital LCMV infections have also been reported . Most importantly, viral Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: . These viruses are also considered to be potential bioterrorism agents . Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers\nPassage: the virus species or can be broadly reactive for New World arenaviruses, depending on the MAb used. Furthermore, the VSV-based pseudotype system provides a safe and rapid tool for measuring virus neutralizing antibody titers, as well as a model to analyze the entry of the respective arenavirus in susceptible cells without using live arenaviruses. Recent discoveries of novel arenavirus species and their potential to evolve predominantly via host switching, rather than with their hosts , suggest that an unknown pathogenic arenavirus may emerge in the future, and that the diagnostic methods for VHF caused by arenaviruses should thus be further Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers\nPassage: arenaviruses.", "Title: A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity\u2014Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings", "Passage: We have demonstrated the ability of an optimized NINA heater prototype, based on exothermic chemical reactions and EPCM, to support isothermal NA amplification assays and established its equivalence to commercially available PCR instruments. The disposable heater described is a component of an instrument-free point of care molecular diagnostics system under development. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that enables electricity-free NA testing for many important analytes. Replicate temperature profiles display minimal variation between runs and far less variation Title: A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity\u2014Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings", "Passage: These results clearly show that the NINA heater can incubate isothermal reactions predictably and precisely with no electricity and without any form of closed-loop control. We also demonstrate that it can be used for LAMP assays, with no discernable difference when compared to two reference heaters, the GeneAmpH 9600 and the ESE-Quant Tube Scanner. There is a bias between the NINA heater and the ESE-Quant , but this is not a significant finding considering we are comparing FIU without any assay calibration. This bias would be easily removed by applying a standard curve. Although we did not intend to rigorously Title: A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity\u2014Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings", "Passage: Heat Production and Temperature in the NINA Heater Ten replicate runs of the optimized prototype displayed minimal variation in temperature from run to run within the reaction tubes . The heater reached the optimal incubation temperature in 15 minutes, and maintained the target temperature with minimal drift over 60 minutes. Comparison of the temperature plots for the CaO, EPCM, and reaction tubes in Figure 1 to Figure 1B in Hatano et al. illustrates the beneficial effect of having the EPCM component in the heater. The CaO temperature traces show rapid and poorly controlled heat generation, with maximum temperatures exceeding 100uC. Title: A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity\u2014Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings", "Passage: device with its attendant requirements. One could also imagine how a properly tuned, stand-alone heater unit could be applicable to any field analytical or preparative method that requires a constant heat source; e.g., cell lysis or temperature-responsive polymer mediated concentration. More compelling is the potential of the NINA heater as the core component of a stand-alone assay kit, capable of providing a result without external electrical power, a reader instrument, or any complex ancillaries. Such a device might include the NINA heater, reaction chambers containing lyophilized reagents, sample metering devices, a readout chamber or lateral flow strip for visible interrogation,", "Title: CDC Summary 21 MAR 2020,\nPassage: The virus that causes COVID-19 is infecting people and spreading easily from person-to-person. Cases have been detected in most countries worldwide and community spread is being detected in a growing number of countries. On March 11, the COVID-19 outbreak was characterized as a pandemic by the WHOexternal icon. Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: It is currently unclear how 2019-nCoV is spread, but it is suspected to be transmitted through contact with infected respiratory secretions, like other known coronaviruses. There are instances of sustained human-to-human transmission across generations of cases, especially near the epicenter in Wuhan City. 21 Current evidence suggests that close contact with an infected person is a major factor in disease transmission. CDC defines \"close contact\" 33 as being in or within two meters of an area with a confirmed patient or being directly exposed to infectious secretions without appropriate PPE. Healthcare facilities in China have reported spread from person to Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Transmission of respiratory viruses generally happens through large respiratory droplets, but some respiratory viruses can spread through fine particle aerosols , and indirect transmission via fomites can also play a role. Coronaviruses can also infect the human gastrointestinal tract , and faecal-oral transmission might also play a role in this instance. The SARS-CoV superspreading event at Amoy Gardens where more than 300 cases were infected was attributed to faecal-oral, then airborne, spread through pressure differentials between contaminated effluent pipes, bathroom floor drains and flushing toilets . The first large identifiable superspreading event during the present 2019-nCoV outbreak has apparently taken Title: CDC Summary 21 MAR 2020,", "Passage: People who get a fever or cough should consider whether they might have COVID-19, depending on where they live, their travel history or other exposures. More than half of the U.S. is seeing some level of community spread of COVID-19. Testing for COVID-19 may be accessed through medical providers or public health departments, but there is no treatment for this virus. Most people have mild illness and are able to recover at home without medical care.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054935/ Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: DOI: 10.1080/22221751.2020.1733440 Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: To claim that it was the lack of transmissibility, rather than the control measures that ended SARS, is not based on any evidence. And it ignores the heroic efforts of affected countries. Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: Authors: Liu, Shan-Lu; Saif, Linda J.; Weiss, Susan R.; Su, Lishan", "Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1\nPassage: In addition to employing our likelihood based method to obtain estimates for the reproductive number and serial interval from the observed data, we also consider various schemes of underreporting among both those surveyed and those not surveyed. Additionally we consider the possibility of overreporting, given that it was later noted that some of the cases reported were actually seasonal flu strains . These reporting patterns are informed using the following pieces of information. Title: Estimating the number of infections and the impact of non-\nPassage: underreporting as well as systematic and country-specific changes in testing. Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1", "Passage: The results of the simulations are given in Figure 1 and 2. Consistent with our theoretical results we observe that when the reporting fraction is constant, the estimates of R0 are unaffected by a failure to control for missingness. However if the reporting fraction increases, then the estimates are smaller when we adjust for the missingness. We also note that has recently described a tendency of this method to overestimate the mean of the serial interval when the serial interval is short, such as in cases of influenza. Thus part of the effect seen could be attributed to this phenomena, Title: Estimating the number of infections and the impact of non-\nPassage: from that date onwards).", "Title: Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada\nPassage: Lower respiratory tract infections in children and infants are common and can require hospitalization; thus, they are a major public health concern. A number of viruses including respiratory syncytial virus , influenza viruses, parainfluenza viruses, rhinovirus, and adenovirus are responsible for LRTIs. In children and infants, RSV is the most common cause; during the first year of life 50%-70% of children will have an RSV infection, and by the third year of age almost all children will have been infected. 1 Neonatal and pediatric LRTIs and RSV are often mild, but can be associated with significant health resource utilization and Title: Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?", "Passage: As for underlying conditions, chronic obstructive pulmonary disease was defined according to the criteria of the 2007 Global Initiative for Chronic Obstructive Lung Disease . Immunosuppressed patients were those with hematologic malignancy , HIV infection, inflammatory diseases under biologic or immunosuppressive treatment and solid organ transplant. As for influenza vaccination, we considered patients who had been vaccinated against influenza within 6 months before admission. Title: Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada", "Passage: Acute bronchiolitis due to RSV was the most frequently listed LRTI as the primary diagnosis followed by acute bronchiolitis, unspecified ; pneumonia, unspecified organism ; bronchopneumonia, unspecified organism ; and acute bronchiolitis due to other specified organisms . Title: Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada\nPassage: Most of the LRTI admissions were for an unspecified viral cause . Pneumonia, organism RSV-specific infections accounted for 1353 cases of LRTI as the primary diagnosis among all children <19 years of age. Most RSV-associated hospitalizations were for acute bronchiolitis due to RSV accounting for 1198 RSV-associated hospitalizations, followed by RSV pneumonia , and acute bronchitis due to RSV .", "Title: DGV: Dengue Genographic Viewer\nPassage: Asian I was predominant in Thailand, whereas genotype Asian American was predominant in Cambodia and Vietnam . From 2001, Asian I increased in Cambodia and Vietnam until finally in 2007 Asian I became the predominant genotype in Indochina. The genotype Asian I viruses in Thailand seemed to be widely disseminated into Vietnam via Cambodia but did not reach Malaysia and Bangladesh . Thus, the Asian American genotype was replaced by Asian I in Cambodia and Vietnam between 1998 and 2011. This example also suggests the idea of genotype transition, which probably reflects the mosquito vector habitat and human activities in Title: DGV: Dengue Genographic Viewer", "Passage: We also found a timeline change in the predominant genotypes. From 1998 to 2007, the dominant genotype in Asia was Cosmopolitan, although India-Pakistan-Sri Lanka and Southeast-Oceania belonged to different lineages . The major genotypes in the Indochina countries were different from those of the other Asian countries; genotype FIGURE 4 | A screenshot of the DENV sequence similarity search. An Env sequence derived from an autochthonous case in Japan was used as a sample query. The query was assigned as the Env region of DENV-1 genotype I. Title: DGV: Dengue Genographic Viewer", "Passage: Intriguingly, when focusing on the genotype instead of the serotype, the data from 2000 to 2014 showed at least three potential geographical genotype distribution border lines in Asia . The first border is between the American continents and other regions , the second is located between Bangladesh and Myanmar for the genotype distributions of DENV-1 and -2 and India and Myanmar for DENV-3, and the third is located between Indochina and the Malay Peninsula . There seem to be differences in the DENV-1 and -3 distributions between Malaysia, Singapore and Indonesia; however, the border line is not clear because Malaysia Title: Genetic diversity of swine influenza viruses isolated from pigs during 2000 to 2005 in Thailand", "Passage: This study also revealed that a human-like swine H3N2, which may have been a provider of the Hb genes, was introduced into the Thai pig population. The Hb genes of the Thai SIVs shared a common ancestor with European and Hong Kong H3 N2 SIVs which possess humanlike surface antigens and avian-like genes encoding internal proteins. SIVs with an avian internal protein gene constellation have been recognized in Europe for H3N2 and H1N2 subtypes since the mid-1980s and -1990s respectively. 4, 22 Although it is not clear when the progeny Hb Thai viruses were introduced into the Thai pig population,", "Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% of clinical subjects, and 6.7% of community subjects . Coronavirus OC43 was the most common virus detected in community members . A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: E/NL63 was detected in 12.5% of the clinical subjects and not detected in the community. Double, triple and quadruple infections were another common feature of note. Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: viruses in the clinical sample and their prevalence in the community. Finally, some of the viruses detected in this study have not been detected and implicated with ARIs in Nigeria. There is no report, to the best of our knowledge, implicating coronavirus in ARIs in Nigeria, and it was detected in 12 subjects in this study. Although cases of double and triple infections were observed in a study in Nigeria in 2011 , as far as we are aware, reports of quadruple infections are rare and have not been reported in Nigeria previously. Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Abstract: OBJECTIVE: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical surveillance in Nigeria. RESULTS: Children were selected via convenience sampling from communities and a tertiary care center during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority of subjects were under 6 years old, of whom 46 were infected . A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: SARS-CoV that includes the split orf8b , civet SARS-CoV , two bat SARS-related-CoV containing full-length orf8 , 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5 ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: The single-stranded RNA genome of the 2019-nCoV was 29891 nucleotides in size, encoding 9860 amino acids. The G + C content was 38%. Similar to other . There are no remarkable differences between the orfs and nsps of 2019-nCoV with those of SARS-CoV . The major distinction between SARSr-CoV and SARS-CoV is in orf3b, Spike and orf8 but especially variable in Spike S1 and orf8 which were previously shown to be recombination hot spots. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Orf8 orf8 is an accessory protein found in the Betacoronavirus lineage B coronaviruses. Human SARS-CoVs isolated from early-phase patients, all civet SARS-CoVs, and other bat SARS-related CoVs contain fulllength orf8 . However, a 29-nucleotide deletion, Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Bat which causes the split of full length of orf8 into putative orf8a and orf8b, has been found in all SARS-CoV isolated from mid-and late-phase human patients . In addition, we have previously identified two bat SARS-related-CoV and proposed that the original SARS-CoV full-length orf8 is acquired from these two bat SARS-related-CoV . Since the SARS-CoV is the closest human pathogenic virus to the 2019-nCoV, we performed phylogenetic analysis and multiple alignments to investigate the orf8 amino acid sequences. The orf8 protein sequences used in the analysis derived from early phase SARS-CoV that includes full-length orf8 , the mid-and late-phase", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: Text: The prevalence of chronic airway inflammatory disease is increasing worldwide especially in developed nations . This disease is characterized by airway inflammation leading to complications such as coughing, wheezing and shortness of breath. The disease can manifest in both the upper airway and lower airway which greatly affect the patients' quality of life . Treatment and management vary greatly in efficacy due to the complexity and heterogeneity of the disease. This is further complicated by the effect of episodic exacerbations of the disease, defined as worsening of disease symptoms including wheeze, cough, breathlessness and chest tightness . Such exacerbations Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: eosinophilic infiltration in the asthmatic airway. The effect is also further compounded by the participation of Th1 and ILC1 cells in the COPD airway; and Th2 and ILC2 cells in the asthmatic airway. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases .", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: of proteins with unique and unknown functions. 12 Moreover, hundreds of human-and avian-infective viruses such as IAV strain H5N1 are known, but recent efforts indicate the true number may be in the millions and many harbour zoonotic potential. 13 It is increasingly clear that host-virus interactions have generated truly vast yet poorly understood and untapped biodiversity. Closing this Special Feature, Watanabe and Kawaoka elaborate on neo-virology, an emerging field engaged in cataloguing and characterising this biodiversity through a global consortium. 14 I predict these efforts will unlock a vast wealth of currently unexplored biodiversity, leading to biotechnologies and treatments that Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses", "Passage: the N alone and maintaining its solubility . The neo-synthesized genomic RNPs then serve either as templates for additional rounds of transcription and/or replication, or are transported to the cell membrane where they are assembled with the M and G proteins into virions, which are then released from the cell through the budding process. Title: N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells", "Passage: in over two decades, though mechanisms limiting its efficacy still occur. 4 Therefore, novel approaches to this disease are necessary. Viral oncolysis is a novel approach to NB that has shown promise in various preclinical cancer models. 5, 6 Despite their promise as therapeutics, oncolytic viruses face application hurdles due to our incomplete understanding of the role of the tumor microenviroment and antiviral immune responses on virotherapy. In general, OVs can selectively kill tumor cells while leaving normal cells intact. 7 They achieve this by exploiting the same cellular defects that promote tumor growth. One of such defects is the Title: N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells", "Passage: Oncolytic viruses are promising new therapies for many cancer types including high-risk NB. 38 However, their application in the clinic could be hampered due to the complexity of the tumor microenviroment and the presence of host immune responses to OVs. It is now understood that the interaction of cancer cells and stroma contribute to cancer progression, metastasis, resistance to chemo drugs, recurrence after treatment, 39, 40 and resistance to virotherapy. 41 Due to the highly heterogeneous nature of NB, it is not surprising if some subpopulations of tumor cells with differences in permissiveness to virus infection or functional IFN signaling", "Title: Animal board invited review: advances in proteomics for animal and food sciences\nPassage: with a special focus on Marek disease , which is of particular interest as a model for human tumours . Title: Deconstructing host-pathogen interactions in Drosophila\nPassage: virulence factors, which is more challenging in intact mammals. Finally, we highlight in Box 1 how studying the effect of toxins can shed light on basic cellular processes. Title: Generalists and Specialists: A New View of How MHC Class I Molecules Fight Infectious Pathogens", "Passage: Finally, much can be learned from evolutionary biology approaches, including observation and simulation, typically with wild outbred populations. For detailed disease associations including autoimmunity and for mechanistic studies, humans and mice are obviously much better suited for rapid progress than chickens. However, at the least, the chicken MHC again has provided a simple model to discover phenomena that have been difficult to discern in both the more complicated MHC of typical mammals and the less well-characterized MHC of wild species. Title: Animal board invited review: advances in proteomics for animal and food sciences", "Passage: Pathogen proteomics Proteomic technologies have also been used to provide novel approaches and insights into the pathogenic mechanisms of bacterial infection in farm animal diseases, which offer unique opportunities to study the proteome of bacterial pathogens during infection . A limited number of proteomic studies have focussed on pathogen responses during clinical intramammary infections discovered major membrane-associated proteins in bovine mastitis S. aureus isolates that could be involved in the recognition of mammary epithelial cell receptors. Tedeschi et al. identified the three highly immunogenic proteins in bovine mastitis S. aureus isolates involved in virulence. Recent proteomic studies investigating different S.", "Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC\nPassage: The transmission of viral particles between humans occurs mainly via direct contact or through a fomite, typically with inoculation into the eye or nose from the fingertip. RVs are able to survive on hands for several hours, which allows an easy human-to-human transmission through this route in the absence of adequate hand hygiene, particularly in the presence of high viral loads . Transmission by large particle aerosols has also been documented, but is presumably less efficient . Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: The transmission of viral particles between humans occurs mainly via direct contact or through a fomite, typically with inoculation into the eye or nose from the fingertip. RVs are able to survive on hands for several hours, which allows an easy human-to-human transmission through this route in the absence of adequate hand hygiene, particularly in the presence of high viral loads . Transmission by large particle aerosols has also been documented, but is presumably less efficient . Title: Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets", "Passage: IAVs can be transmitted via non-mutually exclusive routes of transmission: direct contact, indirect contact, respiratory droplets, or aerosols. However, the relative contribution of each route to efficient IAV transmission remains unknown and under debate. Respiratory droplet transmission is mediated by expelled particles that have a propensity to settle quickly because of their size and is therefore reliant on close proximity between infected and susceptible individuals, usually within 1 m of the site of expulsion 36 . Aerosol transmission is mediated by expelled particles that are smaller in size than respiratory droplets and can remain suspended in the air for prolonged Title: Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets", "Passage: periods of time, allowing infection of susceptible individuals at a greater distance from the site of expulsion. A generally accepted cut-off size to discriminate between respiratory droplets and aerosols is 5 \u00b5m diameter 37 . The current paradigm adopted by the Word Health Organization is that influenza viruses are transmitted via respiratory droplets, when aerosol-generating procedures are excluded 37 . Therefore, current guidelines to prevent influenza virus transmission in health care settings are only based on preventing respiratory droplet transmission . However, the recent body of work on the detection of influenza virus genomes and infectious particles in aerosols suggests", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Noncontaminated CT disinfection procedures after suspected COVID-19 case examination Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Fever-CT disinfection procedures after examination Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: fever-CTs) after these sterilization procedures. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: equipment and prepares to disinfect the imaging equipment immediately after the examination.", "Title: Estimating the number of infections and the impact of non-\nPassage: Lockdown Title: Estimating the number of infections and the impact of non-\nPassage: Lockdown Title: Estimating the number of infections and the impact of non-\nPassage: Lockdown Title: Estimating the number of infections and the impact of non-\nPassage: banned Implemented with lockdown.57 24/3/2020", "Title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: According to a recent study on the three-dimensional structure of IFITM3, there is a C-terminal transmembrane \u03b1-helix and a two-N-terminal intramembrane \u03b1-helices in IFITM3 . There are two splice variants that differ by the presence or absence of the first N-terminal 21 amino acids . Several SNPs including 13 non-synonymous, 13 synonymous, 1 in-frame stop, and 1 splice site acceptoraltering have been reported in the translated IFITM3 sequence . Among them, the rare SNP rs12252C allele of IFITM3 truncates the protein as described above, leading to a reduced inhibition of influenza virus infection in A549 cells . We demonstrated that Title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: Previous studies reveal that the truncated IFITM3 protein produced by SNP rs12252 C allele leads to an impaired anti-influenza activity . To test the functional significance of this polymorphism in HTNV infection, we transfected the majority T or minority C variant IFITM3 alleles that produce full-length or N-terminally truncated proteins with c-myc-tag to HUVEC and A549 cell using lentivirus vectors . Then, we challenged the cells with HTNV at moi = 1 for 24 h and found that cells with the minority C variant were more susceptible to HTNV infection with higher expression of HTNV S segment and more positive Title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: the CC genotype also had higher plasma viral loads compared with those with the CT/TT genotype. Given the impaired function of the IFITM3 protein produced by the C mutation, and the fact that enrichment of the rs12252 C allele in patients with severe disease and the higher viral load in patients with the CC genotype, this founding suggests that IFITM3 plays a pivotal role in the anti-HTNV response in vivo. We speculate that the much higher level of CC allele at healthy population of Han Chinese compared with Caucasians may place the Chinese at a higher risk for developing severe Title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: truncated IFITM3 protein also loses the ability to inhibit HTNV infection in vitro. In Northern European patients hospitalized with seasonal influenza or pandemic influenza A virus, increased homozygosity of the minor C allele of SNP rs12252 in IFITM3 was observed . In Chinese patients infected with influenza A virus, there was also an increased frequency of the C allele and CC genotype of SNP rs12252 . In the present study, we observed an increased frequency of the C allele and CC genotype of SNP rs12252 in severely infected HFRS patients compared with healthy control and mildly affected patients. Patients carrying", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Text: Coronaviruses are spherical, enveloped, and the largest of positive-strand RNA viruses. They have a wide host range, including birds, farm animals, pets, camels, and bats, in which they primarily cause respiratory and gastrointestinal disease. Belonging to the order Nidovirales, family Coronaviridae, and the subfamily Orthocoronaviridae there are four genera of coronaviruses-Alphacoronavirus, Betacoronavirus, Deltacorona virus, and Gammacoronavirus . Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Transmission of respiratory viruses generally happens through large respiratory droplets, but some respiratory viruses can spread through fine particle aerosols , and indirect transmission via fomites can also play a role. Coronaviruses can also infect the human gastrointestinal tract , and faecal-oral transmission might also play a role in this instance. The SARS-CoV superspreading event at Amoy Gardens where more than 300 cases were infected was attributed to faecal-oral, then airborne, spread through pressure differentials between contaminated effluent pipes, bathroom floor drains and flushing toilets . The first large identifiable superspreading event during the present 2019-nCoV outbreak has apparently taken", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV was found and characterized because of its apparent association with severe, and therefore more obvious, illness in humans; we were the canaries in the coal mine. Sero-assays and prospective cohort studies have yet to determine the extent to which milder or asymptomatic cases contribute to MERS-CoV transmission chains. However, transmission of MERS-CoV is defined as sporadic , intra-familial, often healthcare associated, inefficient and requiring close and prolonged contact In a household study, 14 of 280 contacts of 26 MERS-CoV positive index patients were RNA or antibody positive; the rate of general transmission, even in outbreaks is around 3 % Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: of \"contact\" during these interviews has been defined for one study . Despite this lack of clarity, the WHO consider that evidence linking MERS-CoV transmission between DCs to humans is irrefutable . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first WHO case definition defined probable cases of MERS based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract involvement. It also included roles for contact with a probable or confirmed case or for travel or residence within the Arabian Peninsula. If strictly adhered to, only the severe syndrome would be subject to laboratory testing, which was the paradigm early on . From July 2013, the revised WHO case definition included the importance of seeking out and understanding the role of asymptomatic cases and from June 2014, the WHO definition more Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and", "Title: Interferon-\u03b3 Inhibits Ebola Virus Infection\nPassage: Filovirus pathogenesis has been investigated through the use of a variety of different animal models, including mice, guinea pigs, hamsters, and non-human primates . These various model organisms offer different advantages for studying EBOV pathogenesis and assessing novel antiviral treatments. While NHPs are considered the most representative model for EBOV infection as they display very similar symptoms to those observed in humans , they are expensive and, ethically, the use of these animals should be limited to late phase pre-clinical studies. In contrast, infection of mice with MA-EBOV serves as a good, genetically manipulatable small animal model for early phase Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats", "Passage: Text: Members of the Coronaviridae family are enveloped, non-segmented, positive-strand RNA viruses with genome sizes ranging from 26-32 kb . These viruses are classified into two subfamilies: Letovirinae, which contains the only genus: Alphaletovirus; and Orthocoronavirinae , which consists of alpha, beta, gamma, and deltacoronaviruses . Alpha and betacoronaviruses mainly infect mammals and cause human and animal diseases. Gamma-and delta-CoVs mainly infect birds, but some can also infect mammals . Six human CoVs are known to cause human diseases. HCoV-HKU1, HCoV-OC43, HCoV-229E, and HCoV-NL63 commonly cause mild respiratory illness or asymptomatic infection; however, severe acute respiratory syndrome coronavirus and Title: Animals as Reservoir for Human Norovirus", "Passage: upon oral or intragastric inoculation with a high viral dose . Whereas pigs and calves developed diarrhea, both chimpanzees and rhesus macaques did not display any gastrointestinal symptoms. Virus replication was usually found to be restricted to sites of the small intestine. In mice, viral genomes could be amplified from various organs, and in minipiglets, low levels of the virus were additionally found in blood as well as in tonsils, spleen, and lymph nodes . Pathological changes were detectable only in calves and pigs but not in primates. These changes included villous blunting, atrophy, and an increase in inflammatory cells Title: \u03b3\u03b4 T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection", "Passage: treatment methods. In our study, the mice were infected with the HPAI H5N1 virus, which likely induces more severe lung injury than does the H1N1 virus. Moreover, our animal experiments were conducted in TCR-\u03b4 \u2212/\u2212 mice, which completely lack \u03b3\u03b4 T cells; however, \u03b3\u03b4 T cells may not have been completely depleted by the anti-mouse TCR \u03b3\u03b4 mAbs used in the later study.", "Title: Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid\nPassage: strain that is administered orally, and secondly a Vi polysaccharide subunit vaccine administered parenterally. Both these vaccines are only partially effective with studies finding 16-96% efficacy at 3yrs post vaccination for orally administered vaccines and 55-72% at 1.4-3yrs for injectable vaccines . Title: Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid", "Passage: The local response elicited by oral but not IV vaccination prevents bacteria from colonising not only the PP and MLN but also the small intestine and the colon . As bacteria travel out of the colon in the faeces, bacterial numbers in the colon are likely a proxy for the number of bacteria being shed and the risk of transmission from that individual. While orally vaccinated mice have a minimal chance of transmitting secondary infections, as they have almost no detectable bacteria in the gut, IV vaccination provides no reduction in gut colonisation from a secondary infection. This means that Title: Vitamin A deficiency impairs the immune response to intranasal vaccination and RSV infection in neonatal calves", "Passage: increased length of hospital stay for infants receiving VA 58 . We speculate that oral supplementation at the time of vaccination may not be ideal for addressing VAD and its effects on the respiratory immune response, primarily due to kinetics. A similar principle applies to supplementation during acute infection. Changes in VA homeostasis due to acute inflammation likely limits VA access to inflamed tissues and prevents any modulation to the ongoing immune response. Thus, in the future, we are interested in investigating the utility of a mucosal VA supplementation strategy, which may be a more efficient approach to addressing the Title: Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid", "Passage: In contrast, analysis of vaccine growth in the gut-associated organs showed very different patterns of colonisation and clearance based on the method of immunisation. While oral administration of the vaccine strain resulted in colonisation of the mesenteric lymph node and Peyer's patches , intravenous administration rarely resulted in bacteria in these tissues. In the MLN, oral vaccination led to high numbers of bacteria early in the infection, which drops over time, whereas IV vaccination required up to four weeks before bacteria were detected in the majority of mice, and even then only at very low levels . This same pattern", "Title: Estimating the number of infections and the impact of non-\nPassage: to date \u2014 the attack rate - is estimated to be highest in Spain followed by Italy and lowest in Germany Title: Estimating the number of infections and the impact of non-\nPassage: infected to date. Germany is estimated to have one of the lowest attack rates at 0.7% with 600,000 Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: France 3.0%", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: is no evidence that MERS-CoV is a virus of pandemic concern. Nonetheless, hospital settings continue to describe MERS cases and outbreaks in the Arabian Peninsula. As long as we facilitate the spread of MERS-CoV among our most vulnerable populations, the world must remain on alert for cases which may be exported more frequently when a host country with infected camel reservoirs is experiencing human clusters or outbreaks. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Vigilance remains important for containment since MERS-CoV is a virus with a genetic makeup that has been observed for only three years and is not stable. Among all humans reported to be infected, nearly 40 % have died. Continued laboratory testing, sequencing, analysis, timely data sharing and clear communication are essential for such vigilance to be effective. Global alignment of case definitions would further aid accurate calculation of a case fatality ratio by including subclinical case numbers. Whole genome sequencing has been used extensively to study MERS-CoV travel and variation and although it remains a tool for experts, it appears Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: ere is no specific treatment for MERS-CoV. Like most viral infections, the treatment options are supportive and symptomatic . At present, no vaccine exists for preventing the infections of MERS-CoV. e CDC indicated that preventative actions should be taken for any type of respiratory illness . Such actions include washing hands with water and soap for around 20 seconds or using hand sanitizers with alcohol if no water is available. One must cover their nose and mouth during instances of sneezing and coughing with a tissue and avoid touching the mouth, nose, or eyes with their hands until washed properly. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: from areas in Africa where there are camels with a history of MERS-CoV have been reported to date. However,an absence of unexplained pneumonia that may be attributable to MERS-CoV infection may not signal the absence of virus among humans in each country but simply reflect a lack of expensive epidemiology studies conducted by resource-poor countries. It is thus unclear whether MERS-CoV, or an antigenically related CoV, is an unrecognized pathogen in these regions, perhaps circulating for even longer than it has been known in the Arabian Peninsula .", "Title: Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C\nPassage: Hepatitis C Virus is an enveloped positive sense single-stranded RNA virus that infects more than 170 million people . A majority of the individuals infected with HCV develop chronic hepatitis and a proportion will develop cirrhosis and liver carcinoma. HCV remains the most common reason for liver transplantation worldwide . Title: Advanced Molecular Surveillance of Hepatitis C Virus", "Passage: Hepatitis C virus infection is an important global public health problem. Approximately 180 million people are currently infected with HCV , and an alarming number of new infections occur annually . The prevalence of hepatitis C varies significantly worldwide, imposing an important burden in highly endemic countries . HCV infection is commonly associated with chronic liver disease, which frequently results in the advanced stages of cirrhosis and hepatocellular carcinoma following years of silent infection . Title: Interferon Lambda: Opportunities, Risks, and Uncertainties in the Fight Against HCV", "Passage: Hepatitis C virus is a positive sense, single-stranded RNA virus in the family Flaviviridae. It is estimated that as many as 160 million people are chronically infected worldwide with 3-4 million new infections every year . With a global prevalence of 2.35%, estimated to range between 0.14% on the island of Reunion and 14% in Egypt , there is a large economic cost and burden to society. Title: Evidence for Novel Hepaciviruses in Rodents", "Passage: Hepatitis C virus is one of the leading causes of human morbidity and mortality due to hepatitis, liver cirrhosis, and hepatocellular carcinoma . It has become the main reason for liver transplantation in developed countries and represents an economic burden exceeding 1 billion US$ of direct health costs . New estimates of the burden of disease suggest at least 185 million individuals worldwide to have been seropositive in 2005, with a tendency to increase . Treatment has considerably improved due to the optimization of antiviral regimens and the advent of new antiviral drugs . However, treatment in resource-limited settings is", "Title: A real-time spatio-temporal syndromic surveillance system with application to small companion animals\nPassage: End-users of a real-time surveillance system will be responsible for receiving system outputs, interpreting them, and if necessary following up on alarms. Therefore, in addition to flexibility, another important attribute of a surveillance system should be that it reports outcomes in an easily interpretable manner. Our system generates outputs in the form of practice-specific time-series and maps that display the spatio-temporal evolution of GI disease risk over an area of interest in a user-friendly manner; see Fig. 3 . Additionally, we have illustrated the use of a traffic-light device as a visual aid for analysts to quickly identify potential GI Title: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data", "Passage: Some researchers assume that data on the information environmentsuch as Google searches and Twitter feedscan be used as proxies that directly estimate disease transmission in the population as long as the \"signal\" can be separated from the \"noise\" . Others simply view information environment data as a direct proxy for disease transmission. Surveillance systems that are fast, inexpensive, decentralized, automated, and utilize the power of information technology seem to satisfy the need for a magic bullet in the digital era. Whether such systems work as expected, or are another example of \"big data hubris\" , remains an open question. Title: Quantifying the value of surveillance data for improving model predictions of lymphatic filariasis elimination", "Passage: be exploited both scientifically and in management . Specifically, we suggest that these surveillance data need to be analysed using models in a manner that allows the extraction of maximal information about the monitored dynamical systems so that this can be used to better guide both the collection of such data as well as the provision of more precise estimates of the system state for use in making state-dependent decisions . Currently, parasite control programmes use infection monitoring data largely from sentinel sites primarily to determine if an often arbitrarily set target is met . Little consideration is given to Title: A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011\u20132012", "Passage: One of the goals of sentinel influenza surveillance is to minimize the impact of disease by providing useful information to public health authorities so that they may better plan appropriate prevention and control measures . An effective influenza surveillance system should also be able to identify novel or emergent pathogens in the community, and promptly alert health authorities about persons most affected in order to better target programmatic responses. For surveillance to be effective, data collection systems should be able to maintain data integrity, quickly provide analysis-ready data, and be sustainable to run. In the last decade, information and communication", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: The health-evidence.ca registry was used to identify gaps and areas of wealth in the public health review literature. Each of the 21 Focus of Review topic areas were searched, and the quantity and proportion of reviews rated methodologically strong, moderate, and weak were identified. Three categories were used to define availability of reviews within each topic area: few, representing 1-150 reviews; moderate, representing 151-300 reviews; and, many, representing topic areas possessing greater than 301 reviews. Reviews that addressed multiple topics were accounted for within each topic area that they addressed . Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: and how these influence the process warrant a more in-depth examination. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: While well-done reviews in a large number of areas are available, it is important to continue to improve the quality of the overall body of public health review literature. Considering that the majority of weak reviews scored poorly on assessing the methodological quality of the primary studies, transparency, methods for combining or comparing results, conducting a comprehensive search strategy, and data supporting the author's interpretations, review authors should be cognisant of these criteria when conducting systematic reviews. In improving the quality of systematic reviews, the overall goals should ensure there are high quality reviews in all public health topic areas Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: Visitor areas of interest were assessed by summing frequency of visitor searches of the 21 Focus of Review topic areas and visitor use of the topic area browse menu for the period January 1, 2010 to December 31, 2010. Visitor site usage is tracked via Google Analytics, a web analytics tool that collects and aggregates nonpersonal data to report on visitor interaction with the health-evidence.ca website. Total search and browse access by unique visitors were ranked from highest to lowest pageviews. The top 10 areas of interest were summed to generate the denominator: total visitor interest in the top 10", "Title: RNAi Therapeutic Platforms for Lung Diseases\nPassage: The use of aerosols to deliver medication to the lungs has a long history. Administration by inhalation is a popular and non-invasive method of delivering agents into the lungs. There are several inhalation devices available for the delivery of drugs into the lungs. Metered dose inhalers and dry powder inhalers are the most common modes of inhaled delivery. MDIs are the most commonly used inhalers for several lung diseases, such as asthma, bronchitis, and chronic obstructive pulmonary disease , and a spacer is an external device that is attached to an MDI to allow for better drug delivery by enhanced Title: In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery", "Passage: duration at the beginning 50% of inspiratory phase; more studies might be needed to explore different aerosol spray durations to seek for the optimal percentage. Lastly, similar to all the in vitro studies , the manikin's airway did not have physiological functions such as heat and humidify the gas, filter and absorb the medication by the upper airway, etc; additionally, the filter can capture all the aerosol while some aerosol might be exhaled in vivo, contributing to the higher aerosol deposition in the lung with in vitro study. Title: Targeted Versus Continuous Delivery of Volatile Anesthetics During Cholinergic Bronchoconstriction\nPassage: multiple agents, and operational simplicity of the U-PAC vaporizer provides an ideal method for the delivery of inhaled anesthetics in clinical settings, where there are limited options available for administration of these agents to patients . Title: Targeted Versus Continuous Delivery of Volatile Anesthetics During Cholinergic Bronchoconstriction", "Passage: robust estimates of lung mechanics could help to resolve these discrepancies. Nevertheless, although we were unable to detect significant bronchodilation during inhaled anesthetic delivery, our targeted delivery system indicates that it is possible to deliver inhaled anesthetics predominately to the anatomic dead space, resulting in reduced systemic dose. Thus it may be possible to achieve direct pharmacologic action on airway smooth muscle, with less potential for systemic absorption.", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: There are a variety of different methods available for identifying multiple antigens in one sample simultaneously, such as two-dimensional gel electrophoresis , protein chip, mass spectrometry, and suspension array technology . However, the application of these techniques on pathogen detection is still in an early phase, perhaps due to the complicated use and high cost. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Antibody arrays for simultaneous multiple antigen quantification are considered the most accurate methods . Liew validated one multiplex ELISA for the detection of 9 antigens; Anderson used microarray ELISA for multiplex detection of antibodies to tumor antigens in breast cancer, and demonstrated that ELISA-based array assays had the broadest dynamic range and lowest sample volume requirements compared with the other assays. Title: Rapid identification of novel antigens of Salmonella Enteritidis by microarray-based immunoscreening", "Passage: lateral flow test strips are designed with easy handling and read-out in mind. In fact, immunochromogenic strips based on lateral flow have been successfully introduced in the developing countries to detect Treponema pallidum, the cause for the sexually transmitted infection syphilis, among others . Commonly used ELISA systems are based on a sandwich assay format using Anti-O-H antibodies , which detect both the O-antigen and the H-antigen of salmonella. However, in order to improve sensitivity and specificity for future tests, a deeper understanding of specific salmonella antigens is required. Title: Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti", "Passage: Others have shown that combining antibody responses to multiple targets more accurately reflects recent malaria infection than to one antigen though at small increments 4, 31, 32 . The fact that this study showed that multiplex antimalarial antibody data could be collected accurately at scale aids in ensuring representation of the variation in human immune responses. Additional longitudinal studies collecting multiplex antimalarial antibody data following natural infections across varied settings are needed to identify which antigens best reflect exposure histories.", "Title: Estimating the number of infections and the impact of non-\nPassage: to the infection fatality ratio. Title: Clinical review: Mass casualty triage \u2013 pandemic influenza and critical care\nPassage: and case fatality rates during a pandemic, including the potential for more than one wave. The base scenario assumes a clinical attack rate of 25% and a case fatality rate of 0.37%, giving rise to 53,700 excess deaths in the UK. A reasonable worst case scenario involves a cumulative clinical attack rate of 50% with 2.5% case fatality, causing 709,300 excess deaths. Similarly, the US Department of Health and Human Services predicts that in a \"moderate\" scenario based on a virus with 1968-like pathogenicity, 865,000 will require hospitalisation and 65,000 will require ventilation. They also outline a \"severe\" 1918-like scenario Title: Tuberculosis mortality: patient characteristics and causes", "Passage: in the USA reported a TB-related case fatality rate of 0.1%, but more severe forms, such as those with extrapulmonary involvement or a poor performance status, were excluded from the study . TB-related mortality rates in some regions of the world were higher than those in our study. Those are regions with more indigenous groups, poor access to health care or a higher MDRTB percentage, such as South Africa , Australia and Russia . We also found that 82.7% of the deaths were due to non-TB-related causes. This is consistent with previous studies that have shown aging and underlying comorbidities Title: Economic burden of pneumococcal infections in children under 5 years of age", "Passage: that the mortality rate was 119 per 100,000 and the case-fatality rate was 5% for pneumococcal pneumonia; however, for pneumococcal meningitis, the case-fatality rate was as high as 59% despite the mortality rate of 10 per 100,000. Within the European region identified by WHO, the mortality rate was 25 per 100,000 and the case-fatality rate was 5% for pneumococcal pneumonia, whereas these rates were 3 per 100,000 and 38% , respectively, for pneumococcal meningitis. The differences in quality and accessibility of healthcare services may create differences between countries.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: Thus, the unique physicochemical properties of the phage, in combination with modular display of peptides and proteins with known binding specificity, have spawned wholly novel materials with diverse applications. It is worth noting that the unusual biophysical properties of the filamentous phage can also be exploited in the study of structures of other macromolecules. Magnetic alignment of high-concentration filamentous phage in solution can partially order DNA, RNA, proteins, and other biomolecules for measurement of dipolar coupling interactions in NMR spectroscopy. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Thus, the unique physicochemical properties of the phage, in combination with modular display of peptides and proteins with known binding specificity, have spawned wholly novel materials with diverse applications. It is worth noting that the unusual biophysical properties of the filamentous phage can also be exploited in the study of structures of other macromolecules. Magnetic alignment of high-concentration filamentous phage in solution can partially order DNA, RNA, proteins, and other biomolecules for measurement of dipolar coupling interactions in NMR spectroscopy. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date.", "Title: Estimating the number of infections and the impact of non-\nPassage: estimate that interventions across all 11 countries will have averted 59,000 deaths up to 31 March Title: Estimating the number of infections and the impact of non-\nPassage: banned Banning of gatherings of more than 5 people.21 10/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: ordered No in person teaching until 4th of April.52 14/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: ordered Nationwide school closures.23 14/3/2020", "Title: Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant\nPassage: Inflammation-associated cytokines include MCP-1, TNF-\u03b1, IL-1\u03b2, IL-6, IL12p70, and IL-10 . MCP-1, which is monocyte chemoattractant protein-1, recruit monocytes during infection to induce inflammation . TNF-\u03b1 induces inflammation and activates lymphocytes and leukocytes . IL-1\u03b2 is produced by monocytes and macrophages and plays an important role in inflammatory regulation . IL-6 promotes the synthesis of acute-phase proteins, such as CRP, and is produced at the site of inflammation . Overexpression of these pro-inflammatory cytokines may cause excessive inflammation or autoimmune diseases . In this study, there were no statistically significant differences in the levels of the pro-inflammatory cytokines MCP-1, TNF-\u03b1, Title: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity", "Passage: The second cytokine trend that emerged described cytokines that significantly increased following the acute phase. Cytokine profiles that were markedly lower in the acute phase and subsequently increased included IL-1b, TNF-a, IL-12, IL-5, IL-10 and IFN-c . The cytokine increase was more gradual than the previous decreasing trend, where fold changes were generally closer to 2. Both the 6-and 12-month follow-up were statistically increased compared to acute values for IL-5 levels. IL-1b, TNF-a, IL-12, IL-10 and IFN-c had significantly increased by 12 months. Even though the average for these cytokines had also risen by 6 months it was not significant. Title: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity", "Passage: A second host immune response profile was characterized by TNF-a, IL-1b, Il-10, Il-12, IFN-c and IL-5, which increased from the acute phase into convalescence. Interestingly, TNF-a and IL-1b, which are known to co-induce the other's expression, are both involved in chronic inflammatory diseases such as RA, chronic hepatitis B and C infection . Importantly, TNF-a and IL-1b are main contributors to joint pain, which is the major symptom of RA. An internal balance of TNF-a or IL-1b levels is imperative as mis-regulation of either has been shown to be a major proponent of chronic diseases . Our data indicated that Title: A bibliometric analysis of IL-35 research from 2009 to 2018", "Passage: IL-12 and IL-23 are both considered pro-inflammatory cytokines . As an effective T cell immunomodulator, IL-27 has anti-inflammatory and pro-inflammatory properties . Interleukin-35, however, was identified as an inhibitory cytokine in 2007 , indicating that IL-35 is quite different from other members of IL-12 family cytokines. . It has been shown that IL-35 inhibits the proliferation of T cells and induces the conversion of na\u00efve T cells into iTr35 cells . IL-35 activated STAT1/STAT3 by means of an IL-35 receptor, and induced human B cells to transform into regulatory B-cells . After proinflammatory cytokines provoke inflammation, IL-35 can be upregulated", "Title: CDC Summary 21 MAR 2020,\nPassage: Older people and people with severe chronic conditions should take special precautions because they are at higher risk of developing serious COVID-19 illness. Title: CDC Summary 21 MAR 2020,\nPassage: Older adults, with risk increasing by age. Title: CDC Summary 21 MAR 2020,\nPassage: The risk from COVID-19 to Americans can be broken down into risk of exposure versus risk of serious illness and death. Title: CDC Summary 21 MAR 2020,\nPassage: Early information out of China, where COVID-19 first started, shows that some people are at higher risk of getting very sick from this illness. This includes:", "Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?\nPassage: In summary, bacterial and viral co-infections of the respiratory tract are highly lethal and present a dramatic burden for the global health system. The synergy between bacterial and viral infectious agents is related to a variety of factors, including epithelial barrier damage, exaggerated innate immune response, and cytokine storm. Despite many advances in recent years, more knowledge on mechanisms and immunology of disease progression is needed. The synergistic mechanisms between viruses and bacteria leading to enhanced morbidity and mortality are poorly understood. In vivo characterizations of these severe infections are mainly performed in mice which poorly resemble the human physiology Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: In summary, bacterial and viral co-infections of the respiratory tract are highly lethal and present a dramatic burden for the global health system. The synergy between bacterial and viral infectious agents is related to a variety of factors, including epithelial barrier damage, exaggerated innate immune response, and cytokine storm. Despite many advances in recent years, more knowledge on mechanisms and immunology of disease progression is needed. The synergistic mechanisms between viruses and bacteria leading to enhanced morbidity and mortality are poorly understood. In vivo characterizations of these severe infections are mainly performed in mice which poorly resemble the human physiology Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: The clinical significance of viral/bacterial co-infections has long been a controversial topic. While severe bacterial pneumonia following influenza infection has been well described, associations are less clear among infections caused by viruses common in young children; secondary infections due to other viruses are less well understood and has been reviewed by others . Although assessing the overall contribution of bacteria to disease severity is complicated by the presence of many confounding factors in clinical studies, understanding the role of viral/bacterial co-infections in defining the outcome of paediatric ARI may potentially reveal novel treatment and prevention strategies, improving patient outcomes . Title: Confounding roles for type I interferons during bacterial and viral pathogenesis", "Passage: Another important area of research is the interface between viral and bacterial coinfections. The clinical importance of severe bacterial infections occurring after a primary viral infection is well established . Respiratory bacterial infections are more dangerous to patients when they occur following infection with viruses such as influenza and respiratory syncytial virus. This observation has been replicated in mouse models of infection . However, the interaction between viral and bacterial infection is not always deleterious. Infection with herpesvirus induces prolonged IFN-\u03b3 production that leads to protection against infection with L. monocytogenes and Yersinia pestis . The main distinguishing feature between", "Title: Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center\nPassage: Multidrug-resistant organisms and Clostridium difficile are common causes of healthcare-associated infections at hospitals . The contaminated environment is a well-established source for transmission of these organisms . Inadequate room cleaning at wards may increase the risk of acquisition of pathogens for the subsequent occupant. During a 14-month study performed at two intensive care units , patients admitted to rooms where the prior patients carried vancomycinresistant enterococci had documented increased risks of VRE acquisition . A casecontrol study showed that cases who had been exposed to a prior infected or colonized bed occupant had a 5.83-fold increased risk in developing a Title: Contamination during doffing of personal protective equipment by healthcare providers", "Passage: study began. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: The radiology department was divided into four areas : contaminated, semicontaminated, Title: Contamination during doffing of personal protective equipment by healthcare providers\nPassage: Third, contamination sometimes appeared obscure on video and was subject to examiner's decision. Though the examiner reviewed recordings several times from different angles, there could be blind spots and unobservable touches. This could have made the rates underestimated, in other words the false negative rate of the outcome measure could have increased. Also, the video review could have missed subtle contacts. Depending on a single examiner also could have influenced the accuracy of the outcome.", "Title: The Failure of R (0)\nPassage: The basic reproductive ratio-also known as the basic reproductive number, the basic reproduction number, the control reproduction number, or R 0 -is one of the foremost concepts in epidemiology . R 0 is the most widely used epidemiological measurement of the transmission potential in a given population . It is a measure of initial disease spread, such that if R 0 > 1, then the disease can invade an otherwise susceptible population and hence persist, whereas if R 0 < 1, the disease cannot successfully invade and will die out. The concept is defined as the number of secondary infections Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Secondly, the R0, the basic reproduction number, is correctly described as the average number of infections each case causes. But it lacks two key ideas: 1) the 0 after the R implies the native state, which is a fully susceptible population and without any control measures. R is the effectiive number and can include the impact of control measures. Title: Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data", "Passage: The basic reproduction number, R 0 , of an infectious disease is the average number of secondary cases generated by a single primary case in a fully susceptible population . R 0 is the most widely used epidemiological measurement of the transmission potential in a given population. Statistical estimation of R 0 has been performed for various infectious diseases , aiming towards understanding the dynamics of transmission and evolution, and designing effective public health OPEN ACCESS intervention strategies. In particular, R 0 has been used for determining the minimum coverage of immunization, because the threshold condition to prevent a major Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example", "Passage: totally susceptible population . When R 0 is greater than one, there is a likelihood that the infection will to continue to spread; however if R 0 is less than one, then the infection will eventually die out. For this reason, estimating the basic reproduction number is paramount for assessing the effectiveness of different intervention strategies.", "Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: Text: Q fever is a worldwide zoonosis caused by Coxiella burnetii , a small, gram-negative obligate intracellular bacterium. C. burnetii displays antigenic variation with an infectious phase I and less infectious phase II. The primary reservoir from which human infection occurs consists of sheep, goat and cattle. Although C. burnetii infections in animals are usually asymptomatic, they may cause abortions in sheep and goats . High concentrations of C. burnetii can be found in birth products of infected mammals . Humans frequently acquire infection through inhalation of contaminated aerosols from parturient fluids, placenta or wool . Because the infectious dose Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: C. burnetii infection in humans is asymptomatic in approximately 50% of cases. Approximately 5% of cases are hospitalized, and fatal cases are rare . The clinical presentation of acute Q fever is variable and can resemble many other infectious diseases . However, the most frequent clinical manifestation of acute Q fever is a self-limited febrile illness associated with severe headache. Atypical pneumonia and hepatitis are the major clinical manifestations of more severe disease. Acute Q fever may be complicated by meningoencephalitis or myocarditis. Rarely a chronic form of Q fever develops months after the acute illness, most commonly in the Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: Attending physicians were requested to test serum of patients with atypical pneumonia for Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Coxiella burnetii, Influenza A and B, Parainfluenza 1-3, Adenovirus and Enterovirus. Throat swabs were tested for Influenza virus, Adenovirus and SARS-Coronavirus. Laboratory confirmation of an acute Q fever infection was defined as the presence of IgM antibodies against phase II C. burnetii antigens , a 4-fold increase in anti-phase II IgG antibody titer or in anti phase II antibody titer by CF between acute and convalescent sera. A chronic infection was confirmed when both anti-phase I IgG and anti-phase II IgG Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: form of endocarditis . Children develop clinical disease less frequently . Because of its non-specific presentation Q fever can only be suspected on clinical grounds and requires serologic confirmation. While the indirect immunofluorescence assay is considered to be the reference method, complement fixation , ELISA and microagglutination can also be used . Acute infections are diagnosed by elevated IgG and/or IgM anti-phase II antibodies, while raised anti-phase I IgG antibodies are characteristic for chronic infections .", "Title: Clinical review: Update of avian influenza A infections in humans\nPassage: The HA glycoprotein mediates attachment and entry of the virus by binding to sialic acid receptors on the cell surface. The binding affinity of the HA to the host sialic acid allows for the host specificity of influenza A . Avian influenza subtypes prefer to bind to sialic acid linked to galactose by \u03b1-2,3 linkages, which are found in avian intestinal and respiratory epithelium . Human virus subtypes bind to \u03b1-2,6 linkages found in human respiratory epithelium . Swine contain both \u03b1-2,3 and \u03b1-2,6 linkages in their respiratory epithelium, allowing for easy co-infection with both human and avian subtypes . Title: Clinical review: Update of avian influenza A infections in humans", "Passage: The NA glycoprotein allows the spread of the virus by cleaving the glycosidic linkages to sialic acid on host cells and the surface of the virus. The virus is then spread in secretions or other bodily fluids. The NA glycoprotein is not the major target site for neutralization of the virus by antibodies. Title: Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses", "Passage: I nfluenza virus is a rapidly-evolving pathogen that continues to pose a substantial public health burden worldwide despite the availability of licensed vaccines, underscoring the need for more efficacious vaccines. Hemagglutinin is the most prevalent influenza viral surface glycoprotein and engages sialic acid moieties on host cell surface to mediate viral attachment, virus-host membrane fusion and infection 1, 2 . Thus, HA is a primary target for neutralizing antibodies and vaccine design. Based on phylogenetic analysis, influenza A virus HAs can be divided into 18 subtypes and classified as either group 1 or group 2 . Since antibodies that cross-react Title: Label-free sensitive detection of influenza virus using PZT discs with a synthetic sialylglycopolymer receptor layer", "Passage: Several different virus families, including Orthomyxoviridae, Paramyxoviridae and Parvoviridae, use sialoglycoconjugates for attachment . Some viruses bind preferentially to sialic acids attached via a particular glycosidic linkage, and this specificity can contribute to the virus host range, tissue tropism and pathogenesis. Influenza viruses belong to the Orthomyxoviridae, which show a near obligatory dependence on the host cell surface sialoglycoprotein composition for infection. While Influenza B and C are human pathogens and use specific sialic receptors for attachment , Influenza A viruses circulate in a wide range of avian and mammalian hosts, which determine their preferred receptor. Human Influenza A virus", "Title: Of mice and men: the host response to influenza virus infection\nPassage: both human and mouse blood after infection . Our analyses showed that in humans, IFI27 expression steadily increased from 53 h pi until 108.5 h pi in the Woods data set reaching the highest level at 108.5 h . In the Zhai data set, IFI27 expression increased from day 0 to day 2 and then declined on day 4 and day 6 . Expression levels were back to baseline levels on day 21 and post-seasonal . The differences in the timings between the two datasets are due to different definitions of the time post infections. Woods counts the actual time Title: Of mice and men: the host response to influenza virus infection", "Passage: Each year, about 500 million people are infected worldwide by the influenza virus type A and B, of which about 500,000 die . For the diagnosis and treatment of severe IV infections, it is important to determine the infection status and the status of the host response. Detection of virus in nasal swaps by rapid influenza diagnostic tests or by polymerase chain reaction tests is the first step to diagnose an IV infection. However, detection of virus per se in these swabs is not very informative for treatment decisions. It does not provide information on the level of virus replication Title: Of mice and men: the host response to influenza virus infection", "Passage: after infection, whereas Zhai designates the day when patients come into the clinic with symptoms as day 0. In mice, individual CC strains were analyzed and for this comparison, we calculated the mean difference at each day with respect to mock controls. The expression kinetic in the CC mice strains was very similar to that in humans. Expression of Ifi27 increased at day 3 pi and then declined on day 5 pi in most strains . However, individual differences for different strains could be observed. For example, CC001 still had high levels at day 8, whereas CC006 had lower levels Title: Of mice and men: the host response to influenza virus infection\nPassage: and confirmed IFI27 in an independent cohort in humans and shown that dendritic cells activate expression of IFI27 after exposure to IV.", "Title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans\nPassage: Bats, members of the mammalian order Chiroptera, have evolved a range of characteristics that allow them to adapt to changing environmental conditions. They are the only mammals capable of powered flight, most bat species undergo torpor to conserve energy and species that inhabit high northern latitudes hibernate for up to eight months with body temperatures below 10uC . Bats are extremely diverse, making up a fifth of all known mammalian species. They occupy a variety of niches across most of the world where they contribute in many ways to ecological balance . Title: Bat Astroviruses: Towards Understanding the Transmission Dynamics of a Neglected Virus Family", "Passage: after hibernation, may even cause virus persistence in the affected colony . The roosting of certain bat species in gatherings of thousands if not millions of individuals is thought to facilitate high intra-and interspecies contact rates that might allow efficient virus transmission . Deforestation, growing urbanization and environmental changes have not only destroyed great parts of the bats' habitats, but have also increased their interactions with humans and livestock . To analyze the potential health risk for humans, it has become important to study the ecology and the zoonotic potential of viruses found in bats. This review gives an overview Title: Bat Flies and Their Microparasites: Current Knowledge and Distribution", "Passage: Bats are the second most diverse mammalian group after rodents, with \u223c1,390 recognized species across 227 genera . Many bat species play keystone roles in ecosystems, where they are essential to pollination, seed dispersal, and pest control . Several studies have also highlighted their prominent role as pathogen-reservoirs ; viruses being the best studied due to their potential as human pathogens . Bats host more viruses per species than rodents, making them an interesting system for both disease ecology and public health research . Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?", "Passage: attracted by the fruits. Their nocturnal habits will limit the diversity of host they can interact with. We are not aware of any extensive study on the network of potential contacts between bats and other animals during their roosting and feeding behaviour. The majority of studies investigated potential of infectious contact from bats to other organisms . Novel technologies, such as camera traps equipped with nocturnal vision, could provide opportunities for more research on this topic.", "Title: Frequency and Fitness Consequences of Bacteriophage \u03a66 Host Range Mutations\nPassage: High-titer phage lysates were prepared by adding 1 mL stock lysate and bacteria to 3 mL top agar , and pouring onto 35 mL bottom agar in a sterile Petri dish. After 24 hours at 25uC, the resulting plaques were harvested and resuspended in 4 mL of LB, followed by 10 min centrifugation at RCF = 14006g to pellet agar and bacterial debris. Bacteria-free lysates were obtained by filtering the supernatant through a 0.22 mm filter . Phage particles per mL in the lysates were quantified via serial dilution and titering. Plaques were counted on plates where 30-500 plaques were Title: Frequency and Fitness Consequences of Bacteriophage \u03a66 Host Range Mutations", "Passage: We assayed absolute fitness for 13 of our 6 mutants and the wildtype on native and novel hosts using traditional plating methods. Here 10 5 phages were added to 3610 8 host cells in 10 mL LB and incubated at 25uC with rotary shaking for 24 hrs. All assays were replicated 5x. Bacteria-free lysates were obtained by centrifuging 3 mL culture at RCF = 2.756g for 10 min to pellet bacterial debris, then passing the supernatant through a 0.22 mm filter. Phage particles per mL in the lysates were quantified via serial dilution and titering on host lawns. For each Title: Frequency and Fitness Consequences of Bacteriophage \u03a66 Host Range Mutations", "Passage: All phages and bacteria were propagated in lysogeny broth at pH 7. Bacterial cultures were initiated by transferring a single colony from a streak plate into 10 mL LB in a sterile 50 mL flask capped with a 20 mL beaker. Culture flasks were incubated with shaking at 25uC for 18 hours, allowing bacteria to attain stationary-phase density . Title: Frequency and Fitness Consequences of Bacteriophage \u03a66 Host Range Mutations", "Passage: We phenotypically characterized HRM genotypes by determining plaque size on ERA, and by assaying reproductive capacity and attachment rates on ERA and PP. Of our unique mutant genotypes, we did not assay the three mutants whose mutations were not identified . Furthermore, we only assayed one mutant in situations where differences between genotypes were attributable to synonymous amino acid substitutions. Finally, for one mutant, stored frozen lysate degraded due to a freezer failure following sequencing, and viable phage could not be recovered for phenotypic characterization. In sum, we phenotypically characterized 13 of our 17 unique HRM genotypes.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV was found and characterized because of its apparent association with severe, and therefore more obvious, illness in humans; we were the canaries in the coal mine. Sero-assays and prospective cohort studies have yet to determine the extent to which milder or asymptomatic cases contribute to MERS-CoV transmission chains. However, transmission of MERS-CoV is defined as sporadic , intra-familial, often healthcare associated, inefficient and requiring close and prolonged contact In a household study, 14 of 280 contacts of 26 MERS-CoV positive index patients were RNA or antibody positive; the rate of general transmission, even in outbreaks is around 3 % Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: of \"contact\" during these interviews has been defined for one study . Despite this lack of clarity, the WHO consider that evidence linking MERS-CoV transmission between DCs to humans is irrefutable . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first WHO case definition defined probable cases of MERS based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract involvement. It also included roles for contact with a probable or confirmed case or for travel or residence within the Arabian Peninsula. If strictly adhered to, only the severe syndrome would be subject to laboratory testing, which was the paradigm early on . From July 2013, the revised WHO case definition included the importance of seeking out and understanding the role of asymptomatic cases and from June 2014, the WHO definition more Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and", "Title: Chikungunya Virus Fidelity Variants Exhibit Differential Attenuation and Population Diversity in Cell Culture and Adult Mice\nPassage: P \u03fd 0.05; b, P \u03fd 0.01; c, P \u03fd 0.001; d, P \u03fd 0.0001; all other cases, P \u03fe 0.05. limited to the whole genome for 1 mouse and partial genome for the remaining 2 mice per group. Sequencing from LoFi-infected muscle was not possible due to poor PCR amplification. For all isolates, the mean depth of coverage postprocessing ranged from 1,126 to 2,622 . Comparing mutant spectra of CHIKV isolates from ankles by specific nucleotide substitution frequencies, the only significant differences from the WT were greater frequencies of A\u03feC and G\u03feU substitutions in LoFi CHIKV populations . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: CHIKV has been isolated into three genotypes based on phylogenetic studies. These genotypes, based on the gene sequences of an Envelope protein , are Asian, East/Central/ South African, and West African . Using phylogenetic models, Cherian et al. estimate that the Asian genotype of CHIKV emerged between 50 and 310 y ago, and the West and East African genotypes diverged between 100 and 840 y ago . Since then, CHIKV has come a long way, with several mutations incorporated, and has continued to wreak epidemics in several regions. Recent activities of CHIKV include the Indian epidemic in 2005-2006, which was Title: Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses", "Passage: The complete genome sequences of 141 CHIKV isolates were obtained from the National Center for Biotechnology GenBank database . The accession numbers and other detailed information of the selected CHIKVs' genomes, such as isolation date, isolation place, host and genome size were also retrieved . Title: Chikungunya Virus Fidelity Variants Exhibit Differential Attenuation and Population Diversity in Cell Culture and Adult Mice\nPassage: preinoculation. Numbers of feet per group were the following: for CHIKV cohorts 1 to 3 dpi, n \u03ed 32; 4 to 9 dpi, n \u03ed 20; 10 to 11 dpi, n \u03ed 8; for the mock-inoculated group, 1 to 3 dpi, n \u03ed 16; 4 to 9 dpi, n \u03ed 10; 10 to 11 dpi, n \u03ed 4. Adult mouse viremia titers were determined by qRT-PCR of CHIKV RNA in whole blood. Each symbol represents an individual mouse. LOD is the limit of detection. Error bars represent standard deviations. P values for both graphs were calculated by one-way ANOVA. a,", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: NDV has also been explored as a vaccine vector for humans. Two NHP studies assessed the immunogenicity and efficacy of an rNDV expressing the HA or NA of A/Vietnam/1203/2004 . Intranasal and intratracheal delivery of the rNDV-HA or rNDV-NA vaccines induced both serum and mucosal antibody responses and protected from HPAIV challenge . NDV has limited clinical data; however, phase I and phase I/II clinical trials have shown that the NDV vector is well-tolerated, even at high doses delivered intravenously . While these results are promising, additional studies are needed to advance NDV as a human vaccine vector for influenza. Title: Viral vector-based influenza vaccines", "Passage: The first study using NDV as a vaccine vector for influenza was NDV-H1, that expressed the HA gene of influenza virus A/ WSN/1933. Complete protection of mice against homologous challenge infection was achieved, demonstrating that NDV can be used as an influenza vaccine vector. 148 Consequently, a recombinant NDV expressing HA genes of A viruses has been licensed as a poultry vaccine in some countries and was shown to have a protective effect against challenge infection with A viruses in chickens and ducks in various studies. The NDV based A vaccine offered only partial cross-clade protection, but was immunogenic in Title: Viral vector-based influenza vaccines", "Passage: one single study, cross-reactive cellular immune responses against A viruses were observed after vaccination with a NDV-H5 construct. 168 The immunogenicity of recombinant NDV expressing the HA and NA genes of influenza virus A/Vietnam/1203/04 was tested in non-human primates. Both constructs induced VN and local IgA antibody responses and afforded protection from A challenge infection. 169, 170 Small numbers of clinical trials have been performed with NDV, which showed that the vector is well tolerated. Title: Viral vector-based influenza vaccines", "Passage: Newcastle disease virus is a single-stranded negative sense RNA paramyxovirus that causes disease in poultry. NDV has several favorable properties as a vaccine vector; no preexisting immunity in humans exists, NDV can easily be attenuated and reverse genetics systems to rescue recombinant NDV are in place. Thus far, NDV has been extensively characterized as an influenza vaccine vector in poultry, where it serves as a bivalent vaccine capable of inducing immunity against both NDV and influenza virus. As an added advantage, NDV is easily administered to poultry through nasal spray, drinking water or ocular drops. An overview of NDV-based influenza", "Title: Antibody-Mediated \u201cUniversal\u201d Osteoclast Targeting Platform using Calcitonin as a Model Drug\nPassage: This study details the generation of an antibody-mediated osteoclast-targeting platform. This drug-delivery strategy may find utility as \"a universal osteoclast-targeting platform\" in order to directly target and deliver antiresorptive agents, anti-inflammatory agents, cathepsin K inhibitors, disintegrins, H + -ATPase inhibitors, and so on, directly to osteoclast cells. We have shown this platform is capable of being employed as an antiresorptive strategy, and our efforts will now center on the in vivo evaluation of this targeting strategy. Title: Antibody-Mediated \u201cUniversal\u201d Osteoclast Targeting Platform using Calcitonin as a Model Drug", "Passage: functional activity is directly responsible for the generalized bone loss that occurs in rheumatoid arthritis . Thus, we hypothesized that an antiresorptive strategy that selectively targets osteoclasts and/or carries an active drug to osteoclast cells directly would be highly desirable as a therapeutic to treat bone disease involving upregulated osteoclast activity. Title: Antibody-Mediated \u201cUniversal\u201d Osteoclast Targeting Platform using Calcitonin as a Model Drug", "Passage: With the advent of novel RANKL-scavenging antibodybased antiresorptive strategies , it may further prove efficacious to target the RANK receptor directly with an antibody, in order to successfully antagonize receptor signaling and osteoclast function. However, neither the \"scavenging\" nor \"antagonist\" motives of those antiresorptive strategies focus on the targeted delivery of a given drug cargo which would function as a universal osteoclast targeting platform. Title: Antibody-Mediated \u201cUniversal\u201d Osteoclast Targeting Platform using Calcitonin as a Model Drug", "Passage: associated with differing classes of bisphosphonates, the most commonly prescribed medication for osteoporosis . Estrogen hormone replacement therapy stimulates uterine and breast tissue, which predisposes the patient to neoplastic disease . Leg muscle cramps, joint aches and deep vein thrombosis has been associated with selective estrogen receptor modulator therapy . Similarly, conventional salmon calcitonin has shown limitations in antiresorptive efficacy, likely in part because of poor bioavailability to bone cells and the undesired uptake of the drug by calcitonin receptors present in tissues other than bone .", "Title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis\nPassage: intraperitoneal infections, between 25 and 5610 2 pfu of EMCV in 500 ml of PBS were injected into the peritoneal cavity of mice. Mice were monitored daily for weight loss and symptoms of disease. Title: Phleboviruses and the Type I Interferon Response\nPassage: with increased survival after lethal RVFV challenge . Lastly, mice deficient in IFN signaling are more prone to infections with RVFV and PTV . Thus, induction of sufficient amounts of type I IFNs at an early point during infection is crucial for protective effects. Title: Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection", "Passage: as shown in panel D . We analyzed IL-21 expression in pTfh after in vitro stimulation with Leukocyte Activation Cocktail by FACS and RT-PCR. The number of pTfh in the survived, but not the deceased patients showed robust increase in the 1st week, as compared with that in the healthy control , and then gradually decreased in the following two weeks to the baseline , suggesting that pTfh expansion in the early stage of acute SFTVS infection is associated with the recovery of the disease. Moreover, the expression of ICOS, a surface molecule for Tfh migration to GC , showed Title: Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose", "Passage: Vaccine induced CD4 + T cells are known to secrete phagocyte-activating type 1 cytokines like IFN-\u03b3 and TNF\u03b1, which contribute to intracellular antimicrobial defense by activating macrophages . Recent studies suggest that both CD4 + T cells and IFN-\u03b3 play critical roles in combating bacterial infections . The triple antigen fusion TFP846 contains three M.tb antigens: Rv3615c , M.tb10.4 and Rv2660c . Both Rv3615c and M.tb10.4 cover high density of T cell epitopes that promote strong T cell immune response, including functional T cell subsets secreting both IFN-\u03b3 and IL-2 . Rv2660c is stably expressed in the early and late", "Title: The Failure of R (0)\nPassage: that would be calculated assuming exponential lifetimes. They were able to derive limiting values of \u03c6 and used this to gauge the sensitivity of R 0 to dispersion in the underlying distributions. Title: The Failure of R (0)\nPassage: In de Camino-Beck et al. , a graph-theoretic method for calculating R 0 is given. Starting from the definition of R 0 = \u03c1, they derived a series of rules for reducing the digraph associated with F\u03bb \u22121 \u2212 V to a digraph with zero weight, from which \u03bb = R 0 . The rules are as follows. Title: The Failure of R (0)\nPassage: The curve labelled \"Adding and subtracting 9\" illustrates the value R 0,9 as given by . The curve labelled \"Next generation\" illustrates R 0,N , as given by . The curve labelled \"Constant term of the characteristic polynomial\" illustrates R 0,C , as given by . The curve labelled \"Exponential\" illustrates R 0,e , as given by . Title: The Failure of R (0)", "Passage: In this section, we identify some of the more popular methods used to calculate R 0 . We also describe the limitations that each method presents and demonstrate one of the core problems with R 0 . Specifically, we address a key problem with R 0 : how do biologists make sense of it from mathematical models? .)", "Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity\nPassage: The colectomy rate in our study was found to be 7.7%, while the colectomy rate in hospitalized SUC patients reported by the West China Hospital is 17.9%, both are lower than the 20%-40% reported in United Kingdom . Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity\nPassage: significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. Total proctocolectomy with ileal pouch-anal anastomosis was the most commonly employed operation. Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity\nPassage: mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis. Title: Chinese research into severe ulcerative colitis has increased in quantity and complexity", "Passage: no cases of rectal dysplasia and/or cancer was reported after a median 3-year follow-up.", "Title: Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients\nPassage: NDV is an avian paramyxovirus type I which causes a serious disease in chickens and other birds known as ND . NDV outbreaks were first reported in Indonesia, and, subsequently, in Newcastle-upon-Tyne in the year 1926. There have been several panzootics of this disease in poultry and in domestic pigeons during the last four decades . Efforts in controlling the disease involved the development of new vaccines and vaccination protocols . Title: Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients\nPassage: the interferon regulatory factor IRF-9. Title: Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients", "Passage: New viruses or variants can cause epidemics and pose huge public health problems and economic losses within a short time. Title: Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients\nPassage: is transcribed into mRNAs and is translated into viral proteins .", "Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?\nPassage: attracted by the fruits. Their nocturnal habits will limit the diversity of host they can interact with. We are not aware of any extensive study on the network of potential contacts between bats and other animals during their roosting and feeding behaviour. The majority of studies investigated potential of infectious contact from bats to other organisms . Novel technologies, such as camera traps equipped with nocturnal vision, could provide opportunities for more research on this topic. Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?", "Passage: attracted by the fruits. Their nocturnal habits will limit the diversity of host they can interact with. We are not aware of any extensive study on the network of potential contacts between bats and other animals during their roosting and feeding behaviour. The majority of studies investigated potential of infectious contact from bats to other organisms . Novel technologies, such as camera traps equipped with nocturnal vision, could provide opportunities for more research on this topic. Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?\nPassage: other ground-level foraging hosts does not expose bats to the alternative maintenance hosts ). Title: Ebola Virus Maintenance: If Not (Only) Bats, What Else?\nPassage: other ground-level foraging hosts does not expose bats to the alternative maintenance hosts ).", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: both CD4 + and CD8 + T cell responses . The adenovirus vector is another of the most widely evaluated vectors to date to express heterologous antigens, due to ease of production, safety profile, genetic stability, the ease of DNA genome manipulation, and the ability to stimulate both innate and adaptive immune responses and induce both T and B cell responses . They have been extensively examined as a delivery vector in several preclinical and clinical studies for infectious diseases such as anthrax, hepatitis B, human immunodeficiency virus -1, influenza, measles, severe acute respiratory syndrome , malaria and tuberculosis M. Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: an affinity column according to the manufacturer's instructions. Genome structures of vectors were analyzed by restriction digestion of isolated viral DNA and compared with those of the original molecular clones. Particle number and infectivity of vectors were determined by standard optical density reading and immunodetection of the hexon protein, respectively, following infection of 293 cells with limiting dilutions of each vector preparation according to the recommendations by the manufacturer . Purified virus was administered in sterile phosphate buffered saline and had particle to plaque forming unit ratios of 100:1 or less. Title: Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus", "Passage: and four chimpanzee adenovirus vectors, prior immunization with a GFPexpressing construct blocked subsequent responses to the transgene product only for homologous vector; cross-blocking was minimal . Title: Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus\nPassage: Viral particle measurements of adenovirus stocks were made by measurement of absorbance at 260 nm as described .", "Title: Estimating the number of infections and the impact of non-\nPassage: France 3.0% Title: Estimating the number of infections and the impact of non-\nPassage: France measures Advice at the time of lockdown.32 16/03/2020 Title: Estimating the number of infections and the impact of non-\nPassage: 30. Wikipedia. 2020 coronavirus pandemic in France. Wikimedia Foundation Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: of 80,793 confirmed cases and 3,169 deaths on the Chinese mainland. There remain 14,831 Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China\nPassage: 9 1975 10 25 42638 Unknown 26 10 2744 11 26 44653 Unknown 27 11 4515 12 27 46472 58761 28 12 5974 13 28 48467 63851 29 13 7711 14 29 49970 66492 30 14 9692 ----31 15 11791 ---- Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China\nPassage: We shall analyze the daily data for the number of confirmed cases in mainland China, which origins from the National Health Commission of the People's Republic of China . A part of the official diagram is shown in Fig. 1 . For calculations, we have used the data for the period of time from January 16 to February 9, 2020. The numbers shown after February 9 were used for verification of predictions. Title: One Health in China", "Passage: It has been reported that 5,327 cases with 349 deaths occurred in mainland China during the 2003 worldwide SARS epidemic . In 2009, the outbreak of H1N1 caused 164,902 cases and 878 deaths in China . Since the first human H7N9 cases were reported in Guangdong Province in February 2013, up to April 2016, 750 confirmed human cases and 314 deaths have been reported. This could possibly be an even worse threat than H1N1because H7N9 is a low pathogenic avian influenza virus. All pandemics so far have been caused by low pathogenic viruses, and not by high pathogenic viruses .", "Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012\nPassage: R\u00e9union Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean . The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance , based on the surveillance system of mainland France . Influenza activity generally increases during austral winter, corresponding to summer in Europe . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Despite the distance of 9,300 km between R\u00e9union and France, the island is directly connected to Europe with four daily flights to France. These exchanges can impact respiratory pathogens circulation in southern and northern hemisphere. Results of this study can therefore be of interest to both Indian Ocean and Europe countries. Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: Reunion Island is a French overseas department located in the southwestern Indian Ocean, 700 km east of Madagascar and 200 km southwest of Mauritius. The first imported case of pH1N1/2009v was identified on 5 th July 2009 in a traveller returning from Australia. The first case indicating community transmission was detected on 21 st July . pH1N1/2009v became the predominant circulating influenza virus within four weeks of its first detection, its activity peaked during week 35 and ended at week 38 . Contrary to initial fears, the health care system was not overwhelmed, as morbidity and mortality rates were lower Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: the population of Reunion Island and a Chi2 test was used to analyse differences in age, sex and geographic location. Cumulative incidence rates of infection and seroconversion rates were standardized according to the age structure of the community source).", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Spike glycoprotein comprised of S1 and S2 subunits. The S1 subunit contains a signal peptide, followed by an N-terminal domain and receptor-binding domain , while the S2 subunit contains conserved fusion peptide , heptad repeat 1 and 2, transmembrane domain , and cytoplasmic domain . We found that the S2 subunit of 2019-nCoV is highly conserved and shares 99% identity with those of the two bat SARS-like CoVs and human SARS-CoV . Thus the broad spectrum antiviral peptides against S2 would be an important preventive and treatment modality for testing in animal models before clinical trials . Though the S1 Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: subunit of 2019-nCoV shares around 70% identity to that of the two bat SARS-like CoVs and human SARS-CoV ), the core domain of RBD are highly conserved ). Most of the amino acid differences of RBD are located in the external subdomain, which is responsible for the direct interaction with the host receptor. Further investigation of this soluble variable external subdomain region will reveal its receptor usage, interspecies transmission and pathogenesis. Unlike 2019-nCoV and human SARS-CoV, most known bat SARSr-CoVs have two stretches of deletions in the spike receptor binding domain when compared with that of human SARS-CoV. But some Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: bat, civet and human SARS coronaviruses. However, the external subdomain of Spike\u2019s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: As shown in Figure 7 , the SARS-CoV 5 \u2032 -UTR contains SL1, SL2, SL3, SL4, S5, SL5A, SL5B, SL5C, SL6, SL7, and SL8. The SL3 contains trans-cis motif . The SL1, SL2, SL3, SL4, S5, SL5A, SL5B, and SL5C structures were similar among the 2019-nCoV, human SARS-CoV and the bat SARS-related ZC45. In the 2019-nCoV, part of the S5 found was inside Figure 7 Continued the orf1a/b , which was similar to SARS-CoV. In bat SARS-related CoV ZC45, the S5 was not found inside orf1a/b. The 2019-nCoV had the same SL6, SL7, and SL8 as SARS-CoV, and an additional", "Title: Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of Sao Paulo, Brazil, 2009\nPassage: the births. During hospitalization, 8.7% of the live births of cases and 4.2% of live births of controls evolved to death after giving birth. None of the live births of control women who delivered after discharge evolved to death. The median gestational age, birth weight and Apgar score in the 1 st minute were significantly lower among cases than among controls who delivered during hospitalization. Among the cases, 73.7% of the newborns were admitted to the intensive care unit , contrasting to only 35.0% of newborns from controls who delivered during the hospitalization. When the weight of the newborns was Title: HIV testing, test results and factors influencing among infants born to HIV positive mothers in public hospitals of Mekelle City, North Ethiopia: a cross-sectional study", "Passage: The prevalence of HIV among exposed infants can reach up to 45% if left without PMTCT interventions. Nearly two-third of pregnant women living with HIV in the Middle East and North Africa passed the virus onto their infants in the year 2015 alone 10, 11] . In Ethiopia, vertical transmission, which accounted for more than 90% of pediatric HIV, is a very critical issue. Accordingly, HIV related estimates and projections showed that the national estimate of MTCT rate was 25% in 2013 and 17% in 2015. This high magnitude makes HIV/AIDS one of the top priorities of the Health Sector Title: Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of Sao Paulo, Brazil, 2009", "Passage: Among the controls, 13.5% delivered during hospitalization, with one twin birth. Regarding the neonatal outcome in this group, there were 7.7% fetal deaths and 92.3% live births. Considering the live births that occurred during hospitalization, in 100% of cases and in 75.0% of controls a cesarean delivery was performed. The distribution of gestational outcomes shows a concentration of miscarriages and premature births among cases compared to controls who delivered during hospitalization: 82.6% and 45.8%, respectively . Among the 144 controls who were discharged before delivery and who completed a home interview, 100% had live births, 62.5% by cesarean delivery and Title: HIV testing, test results and factors influencing among infants born to HIV positive mothers in public hospitals of Mekelle City, North Ethiopia: a cross-sectional study", "Passage: Mother's adherence status had a significant association with HIV positivity among exposed infants at the 18th month rapid antibody test. Infants born to HIV positive mothers whose adherence status was poor were 15.93 times at higher risk of acquiring HIV infection than infants born to HIV positive mothers whose adherence status was good. The possible risk difference could be due to the fact that poor maternal adherence status causes drug resistance, which then leads to the elevation of maternal viral load, putting exposed infants at high risk of HIV positivity.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: Host resilience to emerging coronaviruses", "Passage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\". Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5", "Title: Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014\nPassage: Handwashing was observed in 29.5% of individuals after using the restroom, increases of 6.0% and 10.4% from 2013 and 2011 , respectively. The highest percentage of handwashing was observed in 2009, a year with an outbreak of a novel influenza strain. Handwashing after restroom use decreased from 72.6% in 2013 to 71.4% in 2014, but handwashing with soap increased from 32.3% to 41.3%. Females washed their hands more often than males . Title: Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014", "Passage: The recent novel influenza outbreak increased social interest in handwashing, and most respondents recognized the effectiveness of handwashing for disease prevention. An increasingly large proportion of respondents had experienced handwashing educational programs or promotional advertisements /pamphlets . Compared to the increased awareness, however, the percentage of respondents actually washing their hands did not increase correspondingly . Title: Associations of hand-washing frequency with incidence of acute respiratory tract infection and influenza-like illness in adults: a population-based study in Sweden", "Passage: A recent Finnish cluster-randomized intervention study found a significant effect of hand-hygiene with soap and water on ARI occurrence, but when the influenza A 2009 pandemic struck, a concurrent nationwide campaign for improved hand hygiene seemingly annulled differences between the intervention arms . Since our study coincided with the influenza pandemic in Sweden we cannot exclude the possibility that temporary changes in hand hygiene habits may have attenuated possible protective effects of the reported habitual washing pattern. However, subanalyses in the influenza highseason and the post-peak season did not reveal any important differences. Interaction between hand-washing and contact behaviour was Title: Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014", "Passage: habits in 2014, a slight increase compared to 2013 . 76.2% of students indicated that they would consider behavioral changes including handwashing after seeing the Ads/pamphlets. Most adults reported having learned to wash their hands correctly after seeing the Ads/pamphlets, compared to 7.8% who did not, a slight increase from 2013 . Nearly nine in 10 students answered affirmatively, vs. 9.6% who did not .", "Title: The Eukaryotic Translation Initiation Factor 4F Complex Restricts Rotavirus Infection via Regulating the Expression of IRF1 and IRF7\nPassage: The genome of rotavirus contains 11 segments encoding 12 proteins including six structural and six non-structural proteins . Among the structural proteins, as a spike protein, rotavirus VP4 plays an essential role in both viral entry and exit . VP4 was also demonstrated to be of importance in viral attachment and internalization , which is often used for the development of rotavirus vaccines . VP4 contains two subunits including a C-terminal subunit VP5* and a N-terminal subunit VP8*, and both VP5* and VP8* help virus entry by interacting with several putative partners and cell surface receptors . The rotavirus genome Title: Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFN\u03b1 Response", "Passage: Rotaviruses are characterized by a triple-layered protein capsid composed of four major structural proteins. Viral protein 2 comprises the innermost layer, in which the dsRNA genome is contained, while the middle layer consists of VP6. The outer layer of the virion is composed of the VP7 glycoprotein and proteasesensitive VP4 spikes . Although both triple-and doublelayered particles are generated during rotavirus replication, only TLPs are infectious, due to the requirements of VP4 and VP7 for cell binding, and trypsin cleavage of VP4 for viral entry and infectivity . Formation of noninfectious empty TLPs and DLPs, which lack the viral genome, Title: The Viruses of Wild Pigeon Droppings", "Passage: The six structural proteins showed best hits by BLASTx to group G rotavirus, first described in chicken feces from Northern Ireland . While VP1-VP3 shared 84%-94% aa-identities with group G rotavirus, other structural proteins showed lower aa-identities, ranging from 35% to 67% . Classification of rotavirus is based mainly on the inner capsid protein VP6 and according to ICTV definition the members of the same rotavirus species should share .60% nt-identity in VP6 region . The sequence of the VP6-encoding genome segment shared 68% nt-identity to group G rotavirus . Direct observation of VP6 alignment between HK18 and its closest Title: Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFN\u03b1 Response\nPassage: is also observed during infection. The nonstructural proteins are involved in viral replication, morphogenesis and assembly, but they are not expressed by nonreplicating virus and are not part of the infectious virion .", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: Koch recognized as early as 1891 that associating the presence of a certain agent with a certain disease is complex, and he therefore postulated guidelines that should be followed before an agent can be classified as a pathogen . His postulates can be summarized in three points: The microbe occurs in every case of the disease in question and under circumstances which can account for the pathological changes and clinical course of the disease; the microbe occurs in no other disease as a fortuitous and nonpathogenic parasite; and , after being fully isolated from the body and repeatedly grown in Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond", "Passage: been made to adjust the Koch's postulates specifically for viruses and the current methodologies deployed , fulfilling these postulates is still not feasible on most occasions due to the lack of an efficient cell culture system, difficulties in antigen synthesis and high levels of viral genetic diversity within viral groups, reviewed in the literature . Title: The social benefits of private infectious disease-risk mitigation\nPassage: The first two axioms imply that P is a matrix of conditional probabilities, and the third implies that it is symmetric. Title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus", "Passage: for the new disease syndrome were unsuccessful, leading to the disease being temporarily designated mystery swine disease in North America. Koch's postulates for MSD were fulfilled in 1991 with a previously unidentified RNA virus discovered in Europe, named Lelystad virus . The discovery was quickly followed by isolation of the virus, initially referred to as swine infertility and respiratory syndrome virus or SIRS virus, in North America .", "Title: Stakeholder views on the acceptability of human infection studies in Malawi\nPassage: To allow participants to reflect and share considered perspectives, we conducted Follow-Up Interview after 2-3 weeks with 3 participants from each FGD to identify any change in views or further reflections. We selected participants for follow-up interviews based on the opinions contributed in FGDs and level of participation, focusing on those who had expressed particularly critical or cautious views that we wanted to explore further, those expressing their views most strongly, and participants who had spoken little during group discussions. This strategy proved useful for ensuring we did not misinterpret original strong opinions and gathered views from those less confident Title: Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study", "Passage: For those who defaulted their follow-up with the research team, an attempt to contact the participant via telephone was made, with a maximum of three attempts. The reasons for defaulting follow-up were elicited and if the patient was admitted, details regarding the admission were obtained. Title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study\nPassage: studies with larger sample sizes should be conducted to verify our preliminary results. Title: A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial\nPassage: 2. After the first negative specimen from a previously positive site, send a repeat specimen from the same site at 48 hours after the first specimen was collected.", "Title: Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017\nPassage: average read coverage was 260-fold for the E-30 genome. Title: Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017", "Passage: using bowtie2/2.3.3.1, primer removal, low-quality and read length filtering using cutadapt 1.18, read duplication removal using a Dedup.py script, de novo assembly using SPAdes 3.7 default parameters, and BLAST search of the resultant contigs . There were a total of 141,329 postprocessing FASTQ reads. The final consensus genome was inspected and annotated using Geneious v10.0.9 . The contig was built from 15,712 reads, assembled to an E-30 reference genome , and deemed nearly complete by comparison to the reference, and the termini were determined as part of the protocol . The total GC content is 48.3% for 7,155 bases. The Title: Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017", "Passage: Data availability. The E-30 sequence of USA/2017/CA-RGDS-1005 has been deposited in GenBank under the accession number MK238483. The quality-filtered FASTQ reads have been deposited in the Sequence Read Archive with the run accession number SRR10082176. Title: Long-read viral metagenomics captures abundant and microdiverse viral populations and their niche-defining genomic islands", "Passage: '-k 500 -more-sensitive -frameshift 15 -subject-cover 20 -evalue 1e-5' Each read fragment had the potential to encode several proteins, along its length, with each putative gene aligning to several similar proteins in the NR database. This information was used to estimate the start and stop loci of each putative gene using an unsupervised learning approach. Identification of the start and stop loci for each putative gene was estimated by hierarchically clustering start and stop loci for each match to an NR protein using Euclidian distance and single linkage. A threshold of 200 bp was used to discriminate between clusters following", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: The shorter nucleocapsid or N protein is a structural component of the viral nucleocapsid, along with the genomic viral RNA segments. As an RNA-binding protein that engages the hairpin termini of the genomic segments with high affinity , it limits the access of the RNA to host nucleases and helps to render viral replication a closed process within the cytoplasm. It also acts as a peripheral membrane protein, as does the L protein , an activity that could play a role in its presumed, but not yet demonstrated function as matrix . Until recently, it had not been appreciated that Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences . N is also reported to interact with actin microfilaments, and the SUMO-1 protein . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: encoded protein in comparison to native mRNAs . N protein has been increasingly linked to viral replication and translation, sometimes in previously unanticipated ways. It is among a growing family of diverse viral proteins that can serve as a nonspecific -RNA chaperone\u2016, an activity that should facilitate the L polymerase's access to vRNA for transcription and replication, in that it can transiently dissociate misfolded RNA structures . Some of N protein's effects on translation might not immediately be recognized to be adaptive in nature. It can replace the entire EIF4F translational initiation complex, simultaneously presenting the ribosome with a replacement Title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling", "Passage: Text: glycoprotein , and viral RNA-dependent polymerase protein , respectively. Humans become infected by inhaling contaminated aerosols or by coming into contact with rodent excreta, and they develop two severe acute diseases, namely, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome . Hantavirus infection affects up to 100,000 to 200,000 humans annually, with fulminant HFRS cases most represented in China . Chinese HFRS cases, mainly caused by Hantaan virus infection, account for approximately 90% of all global cases, with a mortality rate ranging from 0.1 to 15% . Since there is neither an effective therapeutic nor FDA-licensed vaccine, further", "Title: Quantitative Analysis of Cellular Proteome Alterations in CDV-Infected Mink Lung Epithelial Cells\nPassage: As shown in Figure 1A , CPEs in the infection groups became visible at 24 hpi and progressed thereafter. Up to 36 hpi, an obvious CPE was observed and nearly 50 percent of the cells were detached at 48 hpi. The one-step growth curve revealed that the virus load reached a plateau of \u223c4.8 log 10 copy numbers/\u00b5L between 24 and 60 hpi, followed by a gradual decline . Collectively, 24 hpi was considered the optimal time-point for further proteomic analysis, at which a high viral load was maintained and most cells showed little CPE. Virus replication at 6 and Title: Quantitative Analysis of Cellular Proteome Alterations in CDV-Infected Mink Lung Epithelial Cells", "Passage: As a starting point, we determined an optimal time to perform proteomic analysis by monitoring the CPEs and analyzing the one-step viral growth curve in PS-infected Mv.1.Lu cells. The results revealed that PS infection induced serials CPE changes from 12 to 60 hpi, with the virus load exhibiting a plateau between 24 and 60 hpi. Considering the high virus load was maintained at 24 hpi and most cells showed little CPE, we conducted the following proteomic analysis based on 24 hpi. Title: Unified feature association networks through integration of transcriptomic and proteomic data", "Passage: post-infection U937 DENV+Ab infected and 2 hours post-infection U937 DENV + Ab isotype control. With all conditions, timepoints and replicates there were 95 data points comprising this dataset. The virus:antibody/mock mixtures were incubated for 45 minutes in 12-well plates at 37\u02daC. Following this incubation, 1x10 6 U937 or U937+DC-SIGN cells were added and the infection was allowed to proceed for 2 hours at 37\u02daC. The 2 hour time point was collected, and the rest of the cells were centrifuged for 2 minutes at 450XG and resuspended in fresh infection media. The collection timepoints were 2, 8, 16, and 24 hours Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: In the case of PaKiT01 cells infected with rVSV-EBOV, where an apparently persistent infection established, the assay was terminated after 200+ hours of continuous observation. Upon termination of all trials, cells were fixed in formaldehyde , incubated with Hoechst stain , then imaged at 4X on the CellInsight CX5 High Content Screening Platform. The machine was allowed to find optimal focus for each Hoechst stain image. One color channel was permitted such that images produced showed live nuclei in white and dead cells in black.", "Title: Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization\nPassage: All viruses in the genus Flavivirus possess a single-stranded, positive-sense RNA genome of approximately 11 kb . The genome usually encodes a single open reading frame that is flanked by 5' and 3' untranslated regions of ~100 and ~400-700 nt, respectively . The ORF encodes a large polyprotein that is co-and post-translationally cleaved to generate three structural proteins, designated the capsid , premembrane/membrane and envelope proteins, and seven nonstructural proteins in the gene order: 5'-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-2K-NS4B-NS5-3' . The genomes of some flaviviruses appear to encode an additional protein as a consequence of ribosomal frameshifting as discussed later in this review. Title: Viral Interference and Persistence in Mosquito-Borne Flaviviruses", "Passage: Flaviviruses are single stranded-RNA viruses with positive polarity . These viruses are approximately 11 kb in length, with a single open reading frame encoding a polyprotein that is co-and posttranslationally processed 2 Journal of Immunology Research C6/36 Aedes albopictus DENV-2 C6/36 Aedes albopictus JEV C6/36 Aedes albopictus DENV-2 JEV Aal DNV TRA-171 Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: The diameter of hantavirus particles is 80-US210 nm, and the structure is spherical or ovoid. They are composed of 20-30% fat, >50% protein, 7% carbohydrates, and 2% RNA. They are very stable and can survive for more than 18 days at 4 \u2022 C and \u221220 \u2022 C and 10 days at room temperature . The genome comprises three negative sense, single-stranded RNAs that consist the small , medium , and large segments that encode the nucleoprotein , envelope glycoproteins , and viral RNA-dependent RNA polymerase , respectively . The outer membrane of hantavirus is composed of Gn and Gc Title: Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts", "Passage: We identified an incomplete flavivirus-related sequence in sample 7 . Flaviviruses have non-segmented single-stranded positive-sense RNA genomes of around 11 kb. The flavivirus genome contains a long ORF that is translated as a polyprotein. Structural proteins are encoded at the 5' end of the genome and non-structural proteins are encoded at the 3' end.", "Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana\nPassage: Willingness to work during outbreaks and emergencies is deemed a sense of duty even in the face of risk. In this study, less than 50% of HCWs indicated their willingness to work in the event of an EVD outbreak. Additionally, over one third indicated various forms of compensation for themselves or families in case of death or while taking care of an EVD case. This implies that if HCWs are assured or guaranteed that they and or their families would be taken care of in case of death or while taking care of an EVD case, they will willingly work Title: Health workers perceptions and attitude about Ghana\u2019s preparedness towards preventing, containing, and managing Ebola Virus Disease", "Passage: \"If we are assure of some insurance package for people who accept to work in such areas, then I may accept to do that because it is very risky to take care of Ebola patients because we have read on the internet that several health workers have died from the condition\" . Respondents suggested a formal documentation of the insurance package for people who agree to work in EVD treatment centres. Any verbal assurance was deemed unacceptable by respondents. Respondents also indicated the need to consider the families of people who will agree to work in EVD treatment centres in Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: Isolation is a key public health measure to prevent the spread of infectious diseases. In this study, over 97% of HCW indicated their willingness to comply and accept to be isolated in case they became infected after attending to suspected EVD patient. However, a small proportion of HCWs surveyed stated that they would be very unhappy, and this could ultimately affect compliance. Isolation is one of the oldest methods of controlling communicable disease outbreaks for patients . However, it is worthy of note that less that 50% said they would be willing to attend to an EVD suspected patient and Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: The results of this study point to the fact that knowledge and the provision of tools such as personnel protective equipment and other logistics alone is not good enough strategy. There might be the need to as well address issues related to myth, and culture as well as assurances of upkeep should one be infected. The general outlook one's country's devotion to their health staff might be a contributory factor in all of this and cannot be ignored. However, getting HCWs inspired and feel safe in caring for such highly infectious disease outbreaks is critical. During our study, HCWs indicated", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: transcriptomic blueprints for this IFN response are expressed constitutively, even in the absence of stimulation by viral RNA or DNA . In non-flying mammals, constitutive IFN expression would likely elicit widespread inflammation and concomitant immunopathology upon viral infection, but bats support unique adaptations to combat inflammation that may have evolved to mitigate metabolic damage induced during flight . The extent to which constitutive IFN-a expression signifies constitutive antiviral defense in the form of functional IFN-a protein remains unresolved. In bat cells constitutively expressing IFN-a, some protein-stimulated, downstream ISGs appear to be also constitutively expressed, but additional ISG induction is nonetheless Title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis", "Passage: Virus infection of mammals induces the synthesis of type I interferons , which, in turn, inhibit virus replication. The high susceptibility of type I IFN receptor knockout mice to infection by a variety of viruses provides strong evidence for the major role of the IFN system in protecting from viral pathogenesis. In these mice, although IFN is induced by virus infection, it cannot act on target cells. Similarly, in genetically altered mice that are defective in IFN production due to the absence of specific pathogen-associated pattern recognition receptors, signaling proteins or specific transcription factors, viral pathogenesis is enhanced . Although Title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis", "Passage: IFNs are defined by their antiviral activities. They inhibit the replication of many, if not all, viruses mostly by direct inhibition of replication in the infected cells but also by promoting the ability of immune cells to recognize and eliminate the virus-infected cells . The direct effects are mediated by ISGs, which number in the hundreds, and different ISGs are thought to have more potent antiviral activities toward different families of viruses . However, in most cases, it is not known which ISG inhibits the replication of a given virus; the rare exception is the Mx-mediated inhibition of influenza viruses, Title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection", "Passage: To confirm that VLP induction of ISG is dependent on type I IFN signaling, we next tested ISG induction in Ifnar -/mice. As expected, none of the ISGs tested in Fig. 2 were induced in Ifnar -/mice after VLP treatment or EBOV infection . VLPs lower expression of proinflammatory cytokines in EBOV infected mice EBOV pathophysiology such as severe hemorrhagic symptoms and tissue damage is thought to be associated with dysregulated inflammatory cytokine production . Given that VLPs accelerated induction of negative regulatory ISGs, we next evaluated whether VLPs modulate expression of proinflammatory genes. In Fig. 3 , expression of", "Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: Previous studies have shown that the severities of the illnesses caused by avian influenza are linked to host factors, including chronic diseases, immuno-suppressive disorders, delayed confirmation of infection and late antiviral treatment , as well as virus factors such as pathogenicity, replications and mutations . In the present study, we aimed to identify the high risks associated with host factors with regard to fatal outcomes. Title: Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds", "Passage: The H5N1 virus is endemic in poultry and has caused occasional infections in mammals. It poses a severe threat to the poultry industry in Southeast Asia and Africa. However, the mechanism underlying the highly pathogenic manifestation of the H5N1 viruses in chickens has not been fully elucidated. Viruses like influenza are continually exposed to host immune systems, and their pathogenicity is thought to be related to viral replication, which either overwhelms the host immune system or causes it to malfunction. Various viral factors have been shown to be related to differences in pathogenicity. Specific amino acid substitutions in PB2 , Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses", "Passage: generally had significantly higher levels of exposure to poultry, while the secondary cases subsequently became infected after providing care for the ill index patients or after spending prolonged periods of time with them. These findings show that poultry exposure and comorbidities are the major risks of death from the H5N1 virus. Title: Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds\nPassage: As the pathogenesis of HPAIV is complicated and is dependent on various host and viral factors, in this study, we compared the pathogenicity of five genetically related H5N1 viruses isolated from wild birds in Thailand between 2004 and 2005 to that in a commercial chicken breed, White Leghorn. Then, Thai indigenous chickens were inoculated with an H5N1 virus, and their sensitivity to infection and the genetic components related to the host response were examined.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Recombinant vector vaccine evolution", "Passage: The effect of any 'pre-host' evolution on the host immune response is potentially as important as the effect of within-host evolution. An important difference between the two realms is that pre-host evolution may be more easily mitigated than is within-host evolution. That is, controlling pre-host evolution may be a feasible way to limit within-host evolution and to limit the loss of immunity from vaccine evolution. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: All these studies on the effect of pre-existing immunity discuss the impact on humoral responses. Sevil Domenech and colleagues reported that pre-exposing animals to the homologous Salmonella vector leads to a significant reduction in CD8 + responses; however, exposure of animals to a heterologous strain leads to significantly higher CD8 + responses . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: For viral vectors, the impact of cell-mediated immunity was more pronounced, and as depicted in Table 2 , almost always resulted in a reduction in the subsequent immune response. Presumably this is because viruses will induce neutralizing antibody on the first dose, and in subsequent doses this antibody will limit the number of transduced cells, therefore limiting the responses. This is particularly a problem with a common viral vector such as Ad, where a large proportion of the population will have immunological memory against common serotypes . As these authors conclude, it will be possible to utilize such vectors only", "Title: Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine\nPassage: the potential beneficial effects associated with the changes in the cytokine profiles. For instance, the decrease in type I IFN by prior vaccination may reduce its potential adverse effect of increasing the susceptibility to secondary bacterial infections . Prior vaccination with X-31ca before RSV challenge transiently increased the number of eosinophils and neutrophils , which may be responsible for a complex inflammatory response underlying the observed weight loss in the same vaccination/challenge schedule . The generalizability of these findings are limited, however, by the lack of a relevant animal model for influenza and RSV superinfection. Title: Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection", "Passage: to day 2 following infection. Interestingly, challenge with IAV-M2 82 resulted in significantly greater IFN-\u03b3 protein levels in the lung at day 2 and day 4 p.i. as compared to challenge with RSV . In contrast, serum IFN-\u03b3 and lung TNF levels in IAV-M2 82 -infected mice were reduced at day 2 but increased at day 4 p.i. when compared to the levels observed following RSV challenge . Title: Leukemia inhibitory factor protects the lung during respiratory syncytial viral infection", "Passage: which may allow RSV to induce RLRs. Our study observed early cytokine responses following RSV infection and identified a pronounced RIG-I response, which could be lost over time following NS1 or NS2 binding to RIG-I/ MDA5 as reported by others . Also, RSV induction of TLR3 is regulated by RIG-I-dependent IFN-\u03b2 secretions from infected epithelial cells, which is mediated by both IFN response-stimulated element and signal transducer and activator of transcription sites in its proximal promoter . Therefore there are multiple levels of RLRs regulation in RSV infections that can both trigger RLRs responses or subsequently adapt to block RLR-mediated Title: Leukemia inhibitory factor protects the lung during respiratory syncytial viral infection", "Passage: To our knowledge, these findings represent the first evidence that MIF, LIF, CTAK/CCL27, SDF-1\u03b1/CXCL12, SCGF-\u03b2 and SCF are expressed during an RSV infection and LIF signaling is critical to prevent lung damage. Others and we demonstrate that a spectrum of cytokines is released to counter RSV infection 34 ] but further analysis is required to determine the role of these immune responses in RSV pathology. The results of this study demonstrate that RLRs and Trif signaling pathways play major roles in the immune response to RSV infection for both inflammation induction and resolution. Interestingly, 34 of the 42 cytokines examined", "Title: Host and viral traits predict zoonotic spillover from mammals\nPassage: Analyses were limited to terrestrial mammal species as defined by the IUCN Red List and we ran separate analyses for wild and domestic animals. As domestic animals made up a much smaller data set with a unique set of explanatory variables that differed from the wild species analyses, these models were fit separately. Domestic species results are also discussed separately as they are tangential to the primary findings. Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: Organization 32 , and we removed the black rat and domestic mouse from the domesticated list as these two species make up their own 'peri-domestic' category. Host species were categorized as either occurring in human modified habitats or being hunted by humans-both estimates for human contact-according to the IUCN Red List species descriptions 33 . Title: Endemicity and prevalence of multipartite viruses under heterogeneous between-host transmission", "Passage: As customary in compartmental models, we consider that hosts are either free of the virus, and thus susceptible , or infected by a certain combination of the viral forms, translating into various infectious compartments . The main assumption is that a host can be infected only by a combination that guarantees the presence of the full genome. Without it, there is no completion of the viral cycle, and thus no systemic infection is possible. Moreover, we assume that host cells replicate all, and only, the viral forms they are infected by . These assumptions determine the set of existing compartments. Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: In addition to randomly-selected k-fold cross-validation, we evaluated the robustness of our models via a non-random geographic cross-validation, code and summary document provided in our code and data repository. In order to meaningfully organize species in our dataset by geographic areas, we used the 34 zoogeographic regions for terrestrial mammals recently redefined by Holt et al. 55 . Using QGIS 56 , a mammal-specific zoogeographical shapefile provided by Holt's group at the University of Copenhagen was intersected with a shapefile of IUCN's host ranges for all mammals in our database. Areas of these intersections were then calculated using an equal-area", "Title: From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic\nPassage: Relative to the time required for culture and downstream analysis of the data, variation in the speed of different sequencing technologies is relatively modest. There is considerable enthusiasm for the Oxford Nanopore Technology which outputs data in real time, although the ONT requires a comparable amount of time to the popular Illumina Miseq sequencer to generate the same volume of sequence data. Sequencing on the MiSeq sequencer takes between 13 to 56 hours, but as run time correlates with sequence output and read length, researchers tend to systematically favour runs of longer duration. Title: Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing", "Passage: Population-level characterization. HT sequencing technologies provide powerful platforms for investigating the genetic diversity within viral populations, which is integral to our understanding of viral evolution and pathogenesis . Population-level characterization requires very high levels of HT sequencing coverage ; however, the exact level will depend on the background error profiles of the sequencing technology and the desired level of sensitivity. As an example, Wang et al. determined that for pyrosequencing data,~400\u03eb coverage is necessary to identify minor variants present at 1% frequency with 99.999% confidence, and~1,000\u03eb coverage is needed for variants with a frequency of 0.5%. Targeted amplification of the Title: Discovering myeloid cell heterogeneity in the lung by means of next generation sequencing", "Passage: In 1977, Sanger and colleagues published a methodological paper on determining the DNA sequence, providing a tool for deciphering complete genes. This sequencing method, also known as Sanger sequencing, is based on specific chain-terminating inhibitors of DNA polymerase and was subsequently the most widely used sequencing method for the next 30 years. Sanger sequencing was able to obtain the sequence of DNA as long as 1000 bp with high accuracy. However, this low-throughput sequencing method was expensive, time consuming and insufficient to achieve the ultimate goal of deciphering the complicated biological genome. These weaknesses drove the development of high-throughput sequencing: Title: Deep sequencing analysis of viral infection and evolution allows rapid and detailed characterization of viral mutant spectrum", "Passage: of 0.00043 mutations/nucleotide, while the low fidelity variants presented roughly 3-fold more . When all minority variants identified by ViVan were taken into account, regardless of their frequency , the diversity of all three virus populations were significantly higher. Wild type virus, in particular, had higher than expected frequencies of 0.00107 mutations/nucleotide in the region previously sequenced by Gn\u00e4 dig et al., and 0.000996 mutations/nucleotide across the entire genome. These data suggest that the higher sensitivity of HTS identifies more extremely low-frequency variants than would otherwise be detected by other available methods. Indeed, when cut-off thresholds of 0.005 or 0.01", "Title: It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919\nPassage: deaths in the world in that period of time. For example, about 700,000 Germans died from malnutrition-related diseases in the years of 1914-1918. During the 1918-1919 influenza pandemic, between 21 and 25 million people died of influenza worldwide. Those people were killed both directly and indirectly by influenza virus infections. Many families were too poor to buy food and coal, and to afford health care expenses when their family members were ill. Influenza virus could infect all members of a family, and this could result in no one left to feed the fires, and to prepare food for the whole Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: The novel 1918 pandemic virus killed an estimated 50-100 million people within the span of a year , which would equate, given the same degree of lethality, to as many as 400 million or more deaths today. Preventing a repeat of such an unimaginable disaster is a litmus test, and the ultimate standard, for any universal influenza vaccine. Title: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918\u20131919", "Passage: It is postulated that 10% of the worldwide population is infected by an influenza virus each year, resulting in a total economic burden of $87.1 billion USD . As a testament to the significant toll posed by influenza on public health and healthcare systems, the US Centers for Disease Control and Prevention estimated that from 2010 to 2015, influenza infections resulted in 9.23-35.6 million illnesses and 139,000-707,000 hospitalizations annually in the US alone . It has been suggested that children are likely the primary transmitters of influenza . Lethal influenza infections are primarily associated with high risk populations, including infants Title: Influenza, evolution, and the next pandemic", "Passage: The 1918 influenza pandemic is remembered because it killed as many as 50-100 million people worldwide: an estimated 2.5% or more of the global population . Remarkably, the mortality rate was much higher in younger adults than it was in children, giving rise to the familiar W-shaped pandemic mortality curve . A similar mortality pattern has not been described for subsequent pandemics .", "Title: Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch\nPassage: interactions was used. A time step of 2 fs was used with the SHAKE algorithm to constrain all hydrogen bonds in the system. The Berendsen thermostat was used to maintain the temperature and the Berendsen algorithm was used to maintain pressure at 1.0 Pa . A multi-step equilibration protocol including heating to 300 K, short dynamics phases, and multiple minimization phases with gradually decreasing harmonic restraints applied to the RNA molecule was followed by an unrestrained production MD simulation of 40 ns. Title: Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch", "Passage: thus extending and strengthening \u00c9 3, and added Hoogsteen edge interactions between A 9 and G 25 /C 12 , A 8 and G 13 or C 12 , A 7 and U 24 or G 14 , and C 6 and A 22 . These interactions classified with the aid of the DSSR web server underscore the stability provided by multiple hydrogen bonds and the dynamic nature of interactions between alternative partners. Nucleotides G 1 through C 5 and A 111 through A 118 remained single-stranded. Title: Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch", "Passage: flexibility of the residues. Longer run of the samples shown in . Model of TCV118 corresponding to a 25 ns state in a 40 ns-long MD trajectory. 5' end C 6 and A 7 through A 9 form stable Hoogsteen edge interactions with \u00c9 3 . All 3' end nucleotides beyond G 110 remain single stranded. A fragment of this model , comprising C 5 through A 112 , was used as the starting point for all Steered Molecular Dynamics pulling simulations . For this reason, the longer 118 nt fragment that included 5A was used for most of the Title: Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch\nPassage: These results indicate that: in the absence of Mg 2+ , the TSS unfolds in the order of H4b, H5, and H4a/\u00c9 3 ; in the presence of Mg 2+ , the unfolding order is the H4b/H5 complex, followed by H4a/ \u00c9 3 ; the H4b/H5 complex depends on the presence of H4a/\u00c9 3 ; and H4a/\u00c9 3 is substantially more stable than predicted.", "Title: Secretome of Intestinal Bacilli: A Natural Guard against Pathologies\nPassage: The efficacy of Lactobacillus and Bacillus in the prevention and/or treatment of intestinal diseases such as diarrhea, colitis, irritable bowel syndrome, irritable bowel disease, and colorectal cancer was demonstrated . In particular, treatment of colorectal colitis in mice with probiotic B. subtilis restored balance in gut microflora: beneficial species of Bifidobacterium, Lactobacillus, and Butyricicoccus spp. were increased, while gut damage-promoting species of Acinetobacter sp., Ruminococcus sp., Clostridium spp., and Veillonella sp. were decreased . B. subtilis also retained gut barrier integrity, decreased the endotoxin concentration and reduced gut inflammation Bene et al., 2017) . Sporulation of B. subtilis plays a Title: Secretome of Intestinal Bacilli: A Natural Guard against Pathologies", "Passage: Historically, species of Lactobacillus and Bacillus are found in the traditional fermented food products possessing beneficial properties for the intestinal function and are widely used as components of commercially available probiotics: DE111 , Enterogermina , Biosubtyl , Biosporin , BioSpora , Blicheni and Zhengchangsheng , GanedenBC 30 , Lactobacterin , HOWARU or DR20 , Yakult , PCC . In food industry, lactobacilli are applied as starter cultures in the production of fermented milk products, cheese, sausages, bread, kimchi, pickles, and yogurts, the latter accounting for the largest share of sales . The administration of probiotics has been shown to favorably Title: Secretome of Intestinal Bacilli: A Natural Guard against Pathologies", "Passage: For a long time, the representatives of Bacillus genus, unlike the species of Lactobacillus, were not considered as a part of the normal intestinal microbiome. Being isolated from feces, Bacillus spp. as soil microorganisms were considered transient. Recent studies show that they are present in the GIT in the amounts significantly higher than what can be explained by their ingestion with food only. Bacillus spp. have been isolated from the healthy human GIT, where they are well-adapted and are more colonizing than transient . In environment, the vegetative forms of Bacillus are present usually near decomposing plants and in their Title: Secretome of Intestinal Bacilli: A Natural Guard against Pathologies", "Passage: B. subtilis produces surfactins, fengycins and iturins in a ratio of 6:37:57 . The less abundant surfactins unlike other types of Bacillus lipopeptides exhibit a broad range of antimicrobial activities and possess antiviral action . They protect bacilli against extracellular antibiotic-containing vesicles of other species and inhibit phospholipase A2 resulting in subsequent downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines .", "Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data\nPassage: and real cases? Can search engine data serve as a suitable tool for tracking HFMD trends in our pilot study area, Guangdong Province? Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data\nPassage: used to monitor diseases. Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: evidence on health outcomes is reported; and 5) the search strategy is described . To assess the methodological quality, the following ten criteria are used: 1) a clearly focused question was stated; 2) inclusion criteria were explicitly stated; 3) a comprehensive search strategy was described; 4) an adequate number of years were covered in the search; 5) a description of the level of evidence was provided; 6) the methodological rigor of primary studies was conducted and results were described; 7) the methodological quality of primary studies was assessed by two reviewers and the level of agreement was provided; 8) tests Title: Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data\nPassage: revised search volume to examine the predictive effects of the revised search volume.", "Title: T Cell\u2013Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection\nPassage: Production of IL-10 by human macrophages infected with M. tuberculosis has also been shown to inhibit phagosome maturation, resulting in impaired bacterial clearance . Title: T Cell\u2013Derived IL-10 Impairs Host Resistance to Mycobacterium tuberculosis Infection", "Passage: M. tuberculosis infection. Mice deficient in IL-12 , IFN-g , or TNF are not able to build an effective immune response against M. tuberculosis and rapidly succumb to infection. IL-12, produced by APC early during infection, stimulates the differentiation and activation of CD4 + Th1 cells to release IFN-g . In turn, IFN-g activates macrophages to produce TNF and other proinflammatory cytokines, which in combination with IFN-g promote M. tuberculosis killing through the production of reactive oxygen and nitrogen species . Title: Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells", "Passage: including molecular interactions that organize at cellular interfaces of Th cells and GC B cells. Reports have identified numbers of surface molecules implicated in the checkpoint of GC B cell development: CD40-CD40L and ligation play an essential role in class switch recombination and GC formation 44 ; ICOS-B7RP-1 costimulation is critical for production of cytokines lead to B cell activation and differentiation 43 ; CD30-CD153 interactions have an inhibitory effect antibody production in vivo 45 . Together, during the formation of antibody-producing cells, Tfh cells provide necessary help to GC B cells in terms of costimulatory signals and differentiation factors. Title: TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection", "Passage: histocompatibility complex antigens, and induced expression of genes encoding co-stimulation molecules and cytokines. Mature DCs can migrate to lymph nodes where they present antigens and prime na\u00efve T cells 43 , whereas M\u03a6 s are resident cells that have high phagocytic capacities, secrete cytokines, and present antigens to tissue-infiltrating T cells. Our results indicate that FP7 inhibits TLR4-mediated monocyte and DC activation and this could prevent excessive TLR4 signalling involved in inflammatory pathologies.", "Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies\nPassage: MERS was first noted in Saudi Arabia in 2012, and countries around the Arabian Peninsula are now endemic for MERS-CoV. Patients usually present with fever, cough, chills, sore throat, myalgia, and arthralgia rapidly progressing to pneumonia with over 50% of patients requiring intensive care. About one-third of patients present with diarrhea and vomiting, and acute renal impairment is a striking feature of MERS. Risk factors for poor outcome include diabetes, hypertension, and renal and lung disease. Cases have been exported to at least 26 countries with travel occasionally causing cluster of secondary outbreaks. One such example is the MERS-CoV outbreak Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies", "Passage: Severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus are two zoonotic coronaviruses. The SARS pandemic in 2002-2003 resulted in 8096 reported cases in 27 countries. No further SARS cases were reported after the pandemic except isolated cases linked to laboratory accidents. Patients usually presented with fever and respiratory symptoms, but occasionally had diarrhea and vomiting. About 20-30% of SARS patients required mechanical ventilation, with a case fatality rate of about 9% . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: doses, respectively, and was maintained in 79% participants up to study end at week 60. Neutralising antibodies were detected in 50% participants at one or more time points during the study, but only 3% maintained neutralisation activity to end of study. T-cell responses were detected in 71% and 76% participants after 2 and 3 doses, respectively. There were no differences in immune responses between dose groups after 6 weeks and vaccine-induced humoral and cellular responses were respectively detected in 77% and 64% participants at week 60. Title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?", "Passage: 22% of participants across the six trials had documented fever after vaccination, significantly higher than the 8% observed after vaccination with ChAd3 ). Although both vaccines have been evaluated across a range of doses, post-immunization fever levels are an important consideration for a vaccine that may be deployed in an outbreak of a highly febrile illness, such as EVD. In the Geneva trial, 11 of 51 participants developed arthritis lasting a median of 8 days, with virus subsequently identified in synovial joint fluid, indicating peripheral viral replication; two cases of shorter duration were identified among participants in the other studies. Title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?", "Passage: groups both at peak and at day 180, indicating that durability was also comparable . However, in a trial by Ledgerwood et. al., which compared a mixture of ChAd3 ZEBOV and ChAd3 SUDV in a 1 : 1 ratio, each at 1 \u00c2 10 10 or 1 \u00c2 10 11 vp, indicated that a 10-fold higher dose induced significantly higher geometric mean ELISA titres of anti-GP IgG despite similar response rates . In the same trial, 100% of volunteers in the high dose group developed antibody responses against the vaccine strain of Zaire glycoprotein , while only 90% developed responses Title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?\nPassage: In summary, all of the candidate vaccines for EVD that progressed to Phase I studies in response to the 2013-2016 outbreak demonstrated acceptable safety profiles; therefore, describing the magnitude and characteristics of vaccine-induced immunity was the next scientific aim.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The existing practices in detecting genetic material of coronaviruses such as SARS-CoV and MERS-CoV include reverse transcription-polymerase chain reaction , real-time RT-PCR , reverse transcription loop-mediated isothermal amplification and real-time RT-LAMP . Nucleic amplification tests are usually preferred as in the case of MERS-CoV diagnosis as it has the highest sensitivity at the earliest time point in the acute phase of infection . Chinese health authorities have recently posted the full genome of 2019-nCoV in the GenBank and in GISAID portal to facilitate in the detection of the virus . Several laboratory assays have been developed to detect the novel Title: A Microarray Based Approach for the Identification of Common Foodborne Viruses", "Passage: Currently, RT-PCR is the most widely used molecular method for the detection and identification of viruses in biological and environmental sources . Identification of genotypes of virus strains are based on the amplification of specific regions of the viral genome using gene specific primers followed by sequencing of the amplicon by standard procedures . In some instances a preliminary identification is possible using the techniques of single strand conformational polymorphisms or restriction fragment length polymorphisms . Multiplex PCR allows the detection of more than one species of virus in a single analyte . However, these techniques have limitations on sensitivity Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats", "Passage: While whole-genome sequence data may be ideal in the long term for maximizing information about emerging or re-emerging viruses, deep sequencing remains a relatively expensive and time-consuming method. This is especially true when considering the large number of samples that sustained surveillance efforts require. Standardized PCR assays are a quicker, less expensive alternative, but primer sets may fail to capture mutant strains or new viruses. MassTag PCR is a relatively quick and inexpensive tool that has successfully identified novel pathogens, including members of the parvovirus , rhinovirus and arenavirus families. The TIGER broadband pathogen detection system was also extremely useful Title: Anticipating the Species Jump: Surveillance for Emerging Viral Threats", "Passage: While whole-genome sequence data may be ideal in the long term for maximizing information about emerging or re-emerging viruses, deep sequencing remains a relatively expensive and time-consuming method. This is especially true when considering the large number of samples that sustained surveillance efforts require. Standardized PCR assays are a quicker, less expensive alternative, but primer sets may fail to capture mutant strains or new viruses. MassTag PCR is a relatively quick and inexpensive tool that has successfully identified novel pathogens, including members of the parvovirus , rhinovirus and arenavirus families. The TIGER broadband pathogen detection system was also extremely useful", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: Early work with intact vaccinia virus vectors raised safety concerns, as there was substantial reactogenicity that hindered recombinant vaccine development . Two vaccinia vectors were developed to address these safety concerns. The modified vaccinia virus Ankara strain was attenuated by passage 530 times in chick embryo fibroblasts cultures. The second, New York vaccinia virus was a plaque-purified clone of the Copenhagen vaccine strain rationally attenuated by deletion of 18 open reading frames . Title: Virus-Vectored Influenza Virus Vaccines\nPassage: vectors with extensive animal safety and efficacy data may address the issues with preexisting immunity to the human vaccine strains, although the cross-reactivity originally described with cowpox could also limit use. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2 . Poxviruses are also studied extensively as candidate vectors for human use, among which attenuated derivatives of vaccinia virus and New York attenuated vaccinia virus NYVAC strains] are the most promising vectors . They are ideal candidate vectors due to their large DNA-packing capacity and their thermal and genetic stability . The NYVAC vector has been shown to induce CD4 + T cell-dominant responses, and MVA induces Title: Virus-Vectored Influenza Virus Vaccines", "Passage: While there is strong safety and efficacy data for use of NYVAC or MVA-vectored influenza vaccines, preexisting immunity remains a concern. Although the smallpox vaccination campaign has resulted in a population of poxvirus-na\u00ef ve people, the initiation of an MVA or NYVAC vaccination program for HIV, influenza or other pathogens will rapidly reduce this susceptible population. While there is significant interest in development of pox-vectored influenza virus vaccines, current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains. This would likely limit the use and/or efficacy of poxvirus-vectored influenza virus vaccines for regular and seasonal use", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: The principles of the ANFIS are given in this section. The ANFIS model links the fuzzy logic and neural networks . It generates a mapping between the input and output by applying IF-THEN rules . Figure 1 illustrates the ANFIS model where, y and x define the inputs to Layer 1 whereas, O 1i is its output of node i that is computed as follows: Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: series forecasting method was presented for electricity prices based on ANFIS. Svalina et al. proposed an ANFIS based forecasting model for close price indices for a stock market for five days. Ekici and Aksoy presented an ANFIS based building energy consumption forecasting model. More so, ANFIS is also applied to forecast electricity loads . Kumar et al. proposed an ANFIS based model to forecast return products. Ho and Tsai applied ANFIS to forecast product development performance. However, estimating ANFIS parameters is a challenge that needs to be improved. Therefore, in previous studies, some individual swarm intelligence methods have been applied Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: The Adaptive Neuro-Fuzzy Inference System is widely applied in time series prediction and forecasting problems, and it showed good performance in many existing applications. It offers flexibility in determining nonlinearity in the time series data, as well as combining the properties of both artificial neural networks and fuzzy logic systems. It has been applied in various forecasting applications, for example, in , a stock price forecasting model was proposed using ANFIS and empirical mode decomposition. Chen et al. proposed a TAIEX time series forecasting model based on a hybrid of ANFIS and ordered weighted averaging . In , another time Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: This section explains the proposed FPASSA-ANFIS method. It is a time series method for forecasting the confirmed cases of the COVID-19, as given in Figure 2 . The FPASSA-ANFIS utilizes the improved FPA to train the ANFIS model by optimizing its parameters. The FPASSA-ANFIS contains five layers as the classic ANFIS model. Layer 1 contains the input variables . Whereas Layer 5 produces the forecasted values. In the learning phase, the FPASSA is used to select the best weights between Layer 4 and Layer 5.", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: More than 50% of patients who suffer from severe CHIKF are over 65 y old, and more than 33% of them die. Most adults who suffer from severe CHIKF have underlying medical conditions . The other group that is disproportionately affected by severe CHIKV is children. Other complications associated with CHIKV, from most common to least common, include respiratory failure, cardiovascular decompensation, meningoencephalitis, severe acute hepatitis, severe cutaneous effects, other central nervous system problems, and kidney failure . Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: and complications. Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: and complications. Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: During the 2005-2006 La Reunion Island outbreaks, Ramful et al. discovered that mothers could transmit CHIKV to their progeny during the perinatal period , and it is associated with a high degree of morbidity. By mean Day 4 of life, all of the neonates were symptomatic for CHIKV, exhibiting common CHIKF symptoms. Six neonates were confirmed to have contracted CHIKV and developed mengoencephalitis. Of those mothers who, during the La Reunion Island epidemic, were infected long before delivery, only three fetal deaths were reported . Ramful et al. theorized that motherto-child transmission most likely happens transplacentally shortly before delivery . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: A similar study by Gerardin et al. reported nineteen cases of neonatal infection associated with intrapartum maternal viremia that progressed to develop encephalitis owing to vertical transmission from infected mothers .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: Parainfluenza virus type 5 is a paramyxovirus vaccine vector being explored for delivery of influenza and other infectious disease vaccine antigens. PIV5 has only recently been described as a vaccine vector . Similar to other RNA viruses, PIV5 has a number of features that make it an attractive vaccine vector. For example, PIV5 has a stable RNA genome and no DNA phase in virus replication cycle reducing concerns of host genome integration or modification. PIV5 can be grown to very high titers in mammalian vaccine cell culture substrates and is not cytopathic allowing for extended culture and harvest of vaccine Title: Viral vector-based influenza vaccines", "Passage: Parainfluenza virus 5 is, like NDV, a negative sense RNA paramyxovirus that is only recently being explored as an influenza virus vaccine vector . Favorable properties of PIV-5 as a vector include: broad tissue and cell tropism, no clinical disease in humans and availability of reverse genetics systems. Although PIV-5 does not cause disease in humans, PIV-5 has been associated with 'kennel cough' in dogs. 180 In an initial study, vaccination with PIV-5 expressing the HA of an A virus afforded protection against homologous challenge infection. 181 PIV-5 expressing the HA genes of A/ Vietnam/1203/04 and A/Anhui/1/13 also completely protected Title: Virus-Vectored Influenza Virus Vaccines", "Passage: virus . Like NDV, PIV5 has a 3'-to 5' gradient of gene expression and insertion of transgenes at different locations in the genome can variably attenuate the virus and alter transgene expression . PIV5 has broad tropism, infecting many cell types, tissues, and species without causing clinical disease, although PIV5 has been associated with -kennel cough\u2016 in dogs . A reverse genetics system for PIV5 was first used to insert the HA gene from A/Udorn/307/72 into the PIV5 genome between the hemagglutinin-neuraminidase gene and the large polymerase gene. Similar to NDV, the HA was expressed at high levels in infected Title: Viral vector-based influenza vaccines", "Passage: candidate influenza vaccine in other animal models. Furthermore, clinical trials in humans have not been performed with PIV-5 yet, so safety and efficacy data is therefore not available. Finally, little is known about pre-existing immunity to the vector in humans. However, in dogs, a PIV-5 vector vaccine expressing the HA gene of influenza virus could still induce robust antibody responses in the presence of PIV-5-specific immunity. 180 It remains to be determined whether PIV-5 is safe and immunogenic when used in humans.", "Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults\nPassage: Abstract: Human coronavirus is a known cause of influenza\u2010like illness . In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR\u2010positive for HCoV. The distribution of species was as follows: HCoV\u2010OC43 , HCoV\u2010229E , HCoV\u2010NL63 , and HCoV\u2010HKU1 . We did not observe species\u2010specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV\u2010HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness. Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults", "Passage: Authors: Bouvier, Monique; Chen, Wei\u2010Ju; Arnold, John C.; Fairchok, Mary P.; Danaher, Patrick J.; Lalani, Tahaniyat; Malone, Leslie; Mor, Deepika; Ridor\u00e9, Michelande; Burgess, Timothy H.; Millar, Eugene V. Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820427/ Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults\nPassage: DOI: 10.1111/irv.12538", "Title: Early Days of Food and Environmental Virology\nPassage: seemed likely to come, a List was compiled and mailed to everyone on it. New Lists were undertaken at roughly 2-year intervals. This was a time when there were no computers, word processors, or Food Environ Virol 2:1-23 9 Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: Email address Title: 1918 Influenza: the Mother of All Pandemics\nPassage: fax. 301-295-9507; email: taubenberger@afip.osd.mil Title: A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011\u20132012\nPassage: 7 th month of the first year .", "Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission\nPassage: Given the presence of DC-SIGN in the placenta and its known interaction with HIV-1, we hypothesized that polymorphism affecting its expression or function might influence the risk of MTCT of HIV-1. Here, we report significant associations between DC-SIGN genetic variants that modulate DC-SIGN expression in placental macrophages, promote HIV-1 capture and transmission to T cells and increase risk of MTCT among Zimbabwean infants. Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: We have previously investigated the association between DC-SIGN-related genetic variants and MTCT of HIV-1 in the same subset of infants . DC-SIGNR is a DC-SIGN homologue expressed at the cell-surface of endothelial cells of placental capillaries . DC-SIGNR promoter p-198A and intron 2 180A variants were significantly associated with increased risk of MTCT. When adjustment was made for all the significant DC-SIGN and DC-SIGNR associations in logistic regression analysis, DC-SIGN exon 4 242V and DC-SIGNR intron 2 180A variants remained associated with increased risk of IU transmission, suggesting that DC-SIGN and DC-SIGNR are independent predictors of IU of HIV-1 among Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1", "Passage: Given the presence of DC-SIGNR at the maternal-fetal interface and its interaction with HIV-1, we hypothesized that it could influence MTCT of HIV-1. To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of HIV-infected mothers and their infants recruited in Zimbabwe, and identified specific DC-SIGNR variants associated with increased risks of HIV transmission. We further characterized the functional impact of these genetic variants on DC-SIGNR expression and show that they affect both the level and type of DC-SIGNR transcripts produced in the placenta. Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: be the manifestation of HIV-1 placental adaptation to the unique repertoire of cellular targets and increased adherence to C-type lectins which further support the implication of DC-SIGN in IU transmission of HIV-1. However, the net impact of this phenomenon on MTCT of HIV-1 remains to be determined since it has also been shown that placental macrophages can restrict HIV-1 replication .", "Title: Identification of cellular microRNA miR-188-3p with broad-spectrum anti-influenza A virus activity\nPassage: MicroRNAs are a class of~22 nucleotides small regulatory non-coding RNA that are conserved expressed by animals, plants and viruses . They were reported to play a pivotal role in gene regulation by repressing or degrading target mRNA and participate in various cellular process, including cell growth, differentiation, apoptosis, homeostasis, and tumorigenesis . Recently, it has been found that miRNAs also implicated in the regulation of virus invasion . Lecellier et al. reported that miR-32 effectively restricted the accumulation of the retrovirus primate foamy virus type 1 in human cells. Huang et al. reported that the 3\u2032 ends of HIV-1 messenger Title: Zebrafish and Medaka: new model organisms for modern biomedical research", "Passage: MicroRNAs are endogenous single-stranded RNA molecules of 19-30 nucleotides that repress or activate the translation of their target genes through canonical seed-and non-canonical centered miRNA binding sites. The known mechanisms involved in miRNAs-mediated gene silencing are decay of mRNAs and blockage of translation . Probably the expression of 30~50 % of human genes is regulated by miRNAs . Therefore, to understand gene and function in cells or embryos, it is important to exactly know the target gene of a specific miRNA at different phase of cells or at particular stages of developing embryos. Title: Computational Design of Artificial RNA Molecules for Gene Regulation", "Passage: While siRNAs are mainly exogenous molecules, miRNAs instead are a class of RNAi inducers which derive from partially complementary double-stranded hairpin precursors of endogenous origin. Once processed, they are small single-stranded RNAs able to modulate posttranscriptional gene silencing through repression, and at times degradation, of specifi c mRNA target molecules . It has been estimated that miRNA-coding genes represent 1 % of the total gene population, being the biggest class of regulatory molecules. They are present in plants, higher eukaryotes, and in some viruses. miRNAs are often encoded in clusters by genes usually located in introns and, more rarely, in Title: Involvement of microRNAs in physiological and pathological processes in the lung", "Passage: MiRNAs are small non-coding RNAs~22 nucleotides long involved in the negative post-transcriptional gene regulation via RNA interference mechanism . The sequences of miRNAs are highly conserved among plants-microorganisms-animals, suggesting that miRNAs represent a relatively old and important regulatory pathway . MiRNAs belong to the most abundant class of human gene regulators : up to a third of the human genes are regulated by miRNAs . MiRNAs are, therefore, key regulators of numerous genes in biological processes ranging from developmental timing to apoptosis ]. It has been speculated that miRNAs may be associated with the regulation of almost every aspect of", "Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort\nPassage: Exclusion criteria were as follows: patient or legal representative unwilling or unable to give consent; patient under 18 yrs of age; patient pregnant; advanced directive to withhold or withdraw life-sustaining treatment or admitted for palliative care only . Title: Outcome of paediatric intensive care survivors\nPassage: Excluded were: studies in homogeneous PICU populations reporting diagnosis-related outcome in particular but not intensive care treatment as such, and studies evaluating mortality only. Title: Genetic diversity and molecular epidemiology of human rhinoviruses in South Africa\nPassage: were not eligible for enrolment. Title: Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort", "Passage: This study has two important limitations. Firstly participating centres were at liberty to decide which patients they would enrol; subjects were not, therefore, enrolled consecutively, thereby introducing a potential for selection bias. Also there was considerable variation in the number of patients recruited in each country and some centres contributed only small numbers of patients. Nevertheless there was a wide range of ages, severity of physiological derangement and co-morbidities, whereas APACHE II scores and ventilation rates were similar to previous studies, suggesting that a significant, systematic selection bias is unlikely. Secondly, microbiological protocols were not standardised. On the other hand", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In the region of Ar Riyad, including the capital city of Riyadh, a hospital based cluster began, within a single hospital, from late June 2015 . By mid-September there had been approximately170 cases reported but the outbreak appeared to been brought under control in November. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: been rare . In Riyadh-2014, genetic evidence supported the likelihood of multiple external introductions of virus, implicating a range of healthcare facilities in an event that otherwise looked contiguous . Riyadh is a nexus for camel and human travel and has had more MERS cases than any other region of the KSA to date but also harbours a wide range of MERS-CoV variants . However the South Korean outbreak originated from a single infected person, resulting in three to four generations of cases . Studies of this apparently recombinant viral variant did not find an increased evolutionary rate and no Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Our study covered two main regions in Saudi Arabia and provides evidence that the MERS-CoV epidemic in these two regions has specific characteristics that might help future plans for prevention and management of such contagious diseases. Our results showed that only a minority of suspected cases are actually diagnosed with the disease, meaning that the procedures being implemented seemed to be highly sensitive but not highly specific. e majority of confirmed cases were male, aged 41 to 60 years, and presented to healthcare facilities in the summer. Future studies should aim to confirm such findings in other regions in Saudi Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Our data reported a higher prevalence of infection among Saudi nationals as compared with non-Saudi. Another study also showed similar results but with a much higher percentage among Saudis, which may be due to the fact that it included Saudis from all regions . ere is no finding basis for comparison as such, because our study was focused on the Riyadh and Al Qassim regions only.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Kappa-carrageenan and iota-carrageenan were purchased from FMC Biopolymers . The identity, purity of carrageenan subtypes and the molecular weight was confirmed by NMR analysis as described elsewhere and the presence of lambda-carrageenan was below the detection limit of 3%. The dry polymer powders were dissolved in aqua bidest to a final concentration of 2.4 mg/ml iota-and 0.8 mg/ml kappa-carrageenan. This 2x stock solution was sterile filtered through a 0.22 \u03bcm filter and stored at room temperature until use. For further testing the stock solution was diluted to a mixture containing 1.2 mg/ml iota-carrageenan and 0.4 mg/ml kappa-carrageenan . Title: Mannose-Specific Lectins from Marine Algae: Diverse Structural Scaffolds Associated to Common Virucidal and Anti-Cancer Properties", "Passage: Recently, the monoclonal antibody 2G12 was simultaneously produced in rice endosperm with griffithsin and cyanovirin-N and, unexpectedly, extracts of transgenic plants expressing both proteins were shown to display an enhanced in vitro binding to gp120 and synergistic HIV-1 neutralization . Title: Mannose-Specific Lectins from Marine Algae: Diverse Structural Scaffolds Associated to Common Virucidal and Anti-Cancer Properties\nPassage: HFA from Hydropuntia fisheri in complex with a dimannoside , using YASARA. The Ca 2+ ion is colored yellow green. The amino acid sequences of proteins share 27.5% identity and 72.5% similarity, and a RMSD between 176 pruned atom pairs and across all 209 atom pairs were 0.908 \u00c5 and 2.576 \u00c5, respectively, using the Needleman-Wursch alignment algorithm and the BLOSUM 62 homology matrix. Molecular cartoon drawn with Chimera.", "Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: Hantavirus is a virus transmitted mainly by rodent animals, mainly through urine, feces, and saliva and the aerosols produced by them, but rarely by the bites of infected animals . In recent years, the infection rate of hantavirus has increased in China and Europe . Hantavirus disease has turned out to be a newly identified but not a \"new\" disease in Germany . The clinical presentations may vary according to viral strains prevalence in different regions. In Asia, hantavirus infection by Hantan virus and Seoul virus targets mainly the human kidney and causes hemorrhagic fever with renal syndrome . In Title: Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France", "Passage: Hantaviruses are emerging zoonotic pathogens distributed worldwide except in Antarctica . They may cause two severe pathologies in humans: hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome . Viruses of the genus Hantavirus are exceptions within the Bunyaviridae family, in being directly transmitted via aerosols ofsmall mammals excreta with no role for arthropod vectors . Although a growing diversity of hantaviruses has been discovered over the last decade in insectivores and bats , up to now, only rodent-borne hantaviruses have been shown at the origin of human diseases. Hantaviruses are small, enveloped viruses, possessing a tri-segmented RNA genome of Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: In recent years, the repeated outbreak of hantavirus disease has caused a serious threat to human health. The spread of hantavirus from natural hosts to humans is a natural ecological process; however, the outbreak of hantavirus is driven by striped field mouse population cycle dynamics and seasonal climate change . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: The main mechanism by which humans acquire hantavirus infection is by exposure to aerosols of contaminated rodent feces, urine, and saliva . This can occur when humans reside in areas in close proximity to those that rodents inhabit, live in areas infested with rodents, or when rodents invade human settings, which are more frequent in rural habitats. There is a long history of human co-existence with rodents, raising questions about the apparent recent increases in hantavirus-related illnesses, especially HCPS. Other than an apparent association with El Ni\u00f1o southern oscillation events in some regions , the recent increases in incidence of", "Title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection\nPassage: Complete protection offered by i.n. immunization of rAd/NP during heterologous H1N1 or heterosubtypic H3N2 virus challenge rendered us to investigate whether the observed cross-protection correlates with the magnitude NP-specific CD8 T-cell responses, given that influenza NP contains a conserved immunodominant CD8 T-cell epitope as indicated previously. In order to determine the possible presence of such correlation, blood lymphocytes of mice challenged with 10 LD 50 dose of influenza A/Philippines were analyzed by K d /NP 147-155 -tetramer staining from day 0 to day 12 post-challenge. As expected, all animals that received control rAd/Mock immunization or rAd/NP immunization via s.l. route Title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection", "Passage: In our present study, we demonstrated that rAd/NP immunization increases the frequency of NP-specific CD8 T cells recruited to the lungs of i.n. immunized mice following homologous challenge with PR8 virus. Accordingly, complete protection against PR8 challenge was observed only in the groups that received the vaccine virus via i.n. route, indicating that NP-specific CTL response may be directly correlated to protection against homologous influenza virus infection. Moreover, protection against heterosubtypic influenza virus infection may also be correlated to NP-specific CTL response as NP-specific blood CD8 T lymphocyte levels considerably increased in mice that survived the lethal challenge with heterosubtypic Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: detect similar correlations of T-cell reactivity with outcomes was that we had too few infected donors. Protective mechanisms in animal models include antibodies to influenza NP and M2. Although NP is highly conserved, occasional antibodies recognize pH1N1 NP but not NP from seasonal viruses . Our ELISA with polyclonal sera mainly detects the common antibodies to shared epitopes. Therefore, it was not surprising that donor baseline sera had substantial, similar anti-NP antibody titers on pandemic and seasonal sequences. Title: Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection", "Passage: virus titers at day 5 post-challenge were detected at similar levels in all immunization groups . It is probable that rAd/NP may induce long-lasting innate immunity that contributes complementarily with other specific immune arms to the control of the disease by uncharacterized mechanisms . As a result, the protection may not necessarily correlate with virus titers detected in the lungs upon lethal challenge. Overall, these results indicate that i.n. immunization of rAd/NP can confer complete protection against the lethal homologous virus challenge while allowing competent virus replication to perpetuate even to day 5 post-challenge.", "Title: Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future\nPassage: Based on differences in the VP6 protein and/or gene, rotaviruses have been classified into at least 8 groups/species and a tentative 9 th species . Among them, rotavirus-A are the major cause of viral diarrhea in infants and children. RVAs are further classified into G-and P-genotypes on the basis of variations in the antigenically significant outer capsid protein VP7-and VP4encoding gene, respectively . To date, at least 32 G and 47 P genotypes have been reported . Although multiple G-P genotype combinations have been reported in humans so far, G1-G4, G9 and G12 in conjunction with P , P , Title: Rotavirus A in wild and domestic animals from areas with environmental degradation in the Brazilian Amazon", "Passage: The rotavirus belongs to the Reoviridae family and comprises nine species known as Rotavirus group A to I, with a recent proposal of the J species . Rotavirus A is widespread worldwide and predominantly infects humans, bovines and other mammal species, as well as birds . They have a double-stranded ribonucleic acid genome, divided into 11 segments coding for structural proteins and nonstructural proteins . Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Rotavirus is transmitted by the fecal-oral route . Group A rotavirus causes over 600,000 deaths in infants and young children per year, mostly in the developing world . Group B rotaviruses have been predominantly seen in explosive outbreaks in adults in China . Group C rotaviruses do not appear to have public health importance . The prevalence of rotavirus serotypes within these groups vary in different parts of the world making widespread effective disease control extremely difficult . Clinical symptoms include fever and vomiting followed by profuse, watery diarrhea and dehydration . Infections causing acute disease occur predominantly between 6 Title: Species C Rotaviruses in Children with Diarrhea in India, 2010\u20132013: A Potentially Neglected Cause of Acute Gastroenteritis", "Passage: divergence from earlier Indian human RVC isolates. Overall, the findings of this study establish the presence of RVC in the human population of northern India along with insights Figure 7 . Deduced amino acid sequence alignment of the NSP4 genes of the current study HuRVC strain with that of previously-described HuRVC strains. The dots represent the identical amino acids, and five changes were noticed at positions 2, 75, 100, 120, 133 in the current study's RVC isolate, indicated in red boxes.", "Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen\nPassage: years. Archazolid A and B are highly potent and specific inhibitors of v-ATPases . They were first isolated from the myxobacterium Archangium gephyra . These compounds inhibit v-ATPase at low nanomolar concentrations by binding to the subunit c of the V o complex. As their biological activity is comparable to the v-ATPase inhibitors bafilomycin and concanamycin , archazolids are natural compounds of high interest that can be used both as a tool to study the consequences of v-ATPase inhibition and as a lead for drug development. Archazolids can be either produced by fermentation or by total synthesis . Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: recent years. Archazolid A and B are highly potent and specific inhibitors of v-ATPases . They were first isolated from the myxobacterium Archangium gephyra . These compounds inhibit v-ATPase at low nanomolar concentrations by binding to the subunit c of the V o complex. As their biological activity is comparable to the v-ATPase inhibitors bafilomycin and concanamycin , archazolids are natural compounds of high interest that can be used both as a tool to study the consequences of v-ATPase inhibition and as a lead for drug development. Archazolids can be either produced by fermentation or by total synthesis . Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: In the field of cancer research several studies reported on interesting pharmacological effects of archazolid: It reduced the migration of different invasive tumor cells in vitro and cancer cell metastasis in vivo in a breast tumor mouse model . Furthermore, archazolid activated pathways of cellular stress response and apoptosis in highly invasive tumor cells . In classically activated macrophages, archazolid selectively induced the generation of tumor necrosis factor \u03b1 , which may indirectly promote tumor suppression . Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: In the field of cancer research several studies reported on interesting pharmacological effects of archazolid: It reduced the migration of different invasive tumor cells in vitro and cancer cell metastasis in vivo in a breast tumor mouse model . Furthermore, archazolid activated pathways of cellular stress response and apoptosis in highly invasive tumor cells . In classically activated macrophages, archazolid selectively induced the generation of tumor necrosis factor \u03b1 , which may indirectly promote tumor suppression .", "Title: Personal genomes, quantitative dynamic omics and personalized medicine\nPassage: The development of RNA sequencing brought higher coverage, better precision and quantitation, and higher resolution and sensitivity, bringing RNA-Seq technology and transcriptomics on par with genomic sequencing . RNA-Seq considers reads that correspond to millions of transcriptomic fragments that are mapped to the reference genome, to provide information on transcripts that may not be in the existing genomic annotation, allowing the search for novel transcripts, and even identification of SNPs and other variants, while showing remarkable reproducibility . Transcriptome profiling has included looking at cancers , including breast cancer , gastrointestinal tumors and prostate cancer . Title: Automated identification of multiple micro-organisms from resequencing DNA microarrays", "Passage: For both surveillance and diagnostic applications, fine-scale pathogen identification and near-neighbor discrimination is important; therefore, an assay that monitors at this very specific level is desirable for many types of samples such as clinical and environmental . To successfully use any method based on DNA or RNA detection, these assays must be coupled with large databases of nucleic acid sequence information for assay design to ensure that the desired information is provided and for the interpretation of raw data. Several well-established techniques use PCR to amplify individual target pieces of sequenced genomes to provide detection of organisms . These methods Title: A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs", "Passage: Final steps of single-cell RNA analysis are the sequencing and bioinformatic analyses. Alternatives to RNA sequencing are qRT-PCR and microarrays. The former is laborious and has a limited number of targets, while microarrays demand previously established transcriptomic probes and might have some background noise interfering on low abundant transcripts . Thus, the available gold standard method is scRNA-seq. Once sequencing reads are obtained, low-quality bases, adaptors, and barcodes need to be trimmed before alignment. Spike-in controls can be used as quality control and also to estimate the absolute levels of RNA expression since in scRNA-seq the exact number of cells Title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications", "Passage: changes to serve as potential reference markers of the innate responses of influenza infection. Given that RNAseq functions by reading virtually all the RNAs present in the samples tested, we can also discern the magnitude of each RNA change and mark them as the canonical responses. In addition, as RNAseq is not constrained by probe usage as in microarrays, they are therefore more reliable in detecting novel interactions during influenza infections of hNECs. Hence, RNAseq analysis will further augment the transcriptomic data established previously by microarray analysis. The augmented baseline can then be applied to future clinical studies and practice", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: SSA is an optimization technique introduced by . It simulates the Salps' behavior in nature. This behavior is called salp chain. The mathematical model of SSA begins by splinting its population into a leader group and followers group. The leader is the front salp, whereas, the followers are the other salps. The search space is determined in n-dimensions with n variables. Equation works to update the salps' positions. Title: Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden\nPassage: Before 5 years of age When I was between 5 and 14 years old When I was between 15 and 19 years old When I was 20 or older 12. How many siblings do you have? Also count half-siblings and deceased siblings. Title: Mortality, morbidity and health in developed societies: a review of data sources", "Passage: Though social security data are mainly concerned with costs and expenditures, they can sometimes be used for demographic purposes. For example, Lauderdale and Kestenbaum have used data from the US Social Security Administration for estimating age-and sex-specific death probabilities for the elderly of six Asian American subgroups, avoiding numerator/denominator bias when these are provided by different sources. In particular, the issue of determining age for the foreign-born and for immigrants was dealt with. Title: Seasonal distribution of active systemic lupus erythematosus and its correlation with meteorological factors\nPassage: Between January 1997 and December 2006, there were 640 patients who conformed to the diagnostic criteria for SLE and had a SLEDAI score of $10. Results indicated that the number of patients with active SLE was highest in winter and lowest at the junction between summer and autumn . Distribution of the 640 patients over 12 months is shown in Figure 1 and Table 1 .", "Title: A Microarray Based Approach for the Identification of Common Foodborne Viruses\nPassage: Currently, RT-PCR is the most widely used molecular method for the detection and identification of viruses in biological and environmental sources . Identification of genotypes of virus strains are based on the amplification of specific regions of the viral genome using gene specific primers followed by sequencing of the amplicon by standard procedures . In some instances a preliminary identification is possible using the techniques of single strand conformational polymorphisms or restriction fragment length polymorphisms . Multiplex PCR allows the detection of more than one species of virus in a single analyte . However, these techniques have limitations on sensitivity Title: Application of Molecular Diagnostic Techniques for Viral Testing", "Passage: These techniques use enzyme-mediated processes, in which the enzymes synthesize several copies of target nucleic acid. The amplification products are detected by two oligonucleotide primers that bind to complementary sequences. The final result is the production of millions of copies of the targeted sequence. There is possibility of contamination, so false positive results must be reduced through special laboratory design, practices and workflow. Title: Application of Molecular Diagnostic Techniques for Viral Testing\nPassage: The beginning of molecular diagnostics was initiated at the end of the eighties with the development of the PCR . Although this method is the most widely used nucleic acid amplification technique, other methodologies have been developed. The biochemical mechanisms of these techniques are based on target, signal or probe amplification. Title: Application of Molecular Diagnostic Techniques for Viral Testing", "Passage: fast, linear, isothermal and simple compared with other DNA detection methods.", "Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection\nPassage: As discussed, cytokines such as IL-4, IL-13 and IL-10 can boost protein production in mucin-secreting goblet cells. 54, 75, 76 There are several reports of correlations of cytokine levels with disease; however, limited research has been done on the direct effect of cytokines on protein biosynthesis. Title: An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation", "Passage: downstream components of the IFN signaling pathway. Lung tissues from the same infected mice used for the original gene expression analysis were subjected to cytokine array analysis. Thirty-two cytokine protein concentrations were measured and log scaled , and the average fold change relative to uninfected, time-matched lung samples was determined. The heat map illustrates protein expression values for the 17 cytokines that had transcripts assigned to the N1 module were set to zero); of these, 15 exhibited expression profiles that were highly significantly correlated with the corresponding transcript and the N1 module eigengene . Non-N1 cytokines are shown in S6 Title: Assessment of immune organ dysfunction in critical illness: utility of innate immune response markers", "Passage: Key cytokines: serum levels of IL-6, IL-10, and TNF-\u03b1 Serum cytokine levels are routinely assessed in some institutions for earlier recognition, estimation of prognosis, and follow-up of critically ill patients. However, it should be noted that they do not reflect immune cell functionality as cytokines are mostly pleiotropic, derived from different cells including non-immune cells, may be counteracted by natural inhibitors , and have variable clearance rates . In the following, we discuss three cytokines with pathophysiologic and/or diagnostic relevance in critical illness: IL-6 is a potent pleiotropic cytokine with mainly pro-inflammatory effector function. IL-6 is expressed by monocytes/macrophages, endothelial Title: Evaluation of Approaches to Identify the Targets of Cellular Immunity on a Proteome-Wide Scale", "Passage: 1.8-fold for IFN-c, 2.6-fold for IL-10 and 7-fold for TNF-a. The most robust and specific antigen-specific IFN-c and TNF-a responses were detected at the highest dilution of IVTT product, where background E. coli responses were lowest. This is a favorable scenario for proteomic-wide scale cellular screening, as the use of highly diluted IVTT products is more cost-effective. Unexpectedly, poor results were obtained with ELIspot wells precoated with anti-IFN-c mAb as well as anti-HIS mAb to bind the HIS tag on the IVTT product. In vivo studies with PyCSP IVTT products confirmed that the target protein was produced and that the", "Title: Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1\nPassage: spillover . In humans, VEEV causes a febrile illness typified by fever, malaise, and vomiting. In some cases, infection progresses to the central nervous system and neurological symptoms, such as confusion, ataxia, and seizures, manifest. The mortality rate among cases with neurological symptoms can be as high as 35% in children and 10% in adults, with long-term neurological deficits often being seen in survivors . In 1995, an outbreak of VEEV in Colombia and Venezuela resulted in over 100,000 human cases . In addition to natural outbreaks, VEEV is also a concern from a bioterrorism perspective, as it can be Title: Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas", "Passage: hundreds-of-thousands of cases over a period of months to a few years. Prior to the 1980s, VEE epizootics involving high case-fatality rates were frequently recorded. Because horses have been an important component of the local agricultural economies within many Latin American regions, VEE has often had a sizeable economic impact as well as a direct effect on public and veterinary health . Recent outbreaks during the 1990s in Venezuela, Colombia and Mexico have demonstrated the potential for VEEV to re-emerge periodically from enzootic progenitors . The emergence of VEEV into an epidemic/ epizootic form has been associated with specific mutations Title: Treatment of Neuroterrorism", "Passage: Venezuelan equine encephalitis virus is an alphavirus that is most commonly found in Central and South America. It is transmitted to humans by mosquitoes. In case of a bioterrorist attack, the distribution would be made through aerosols . The virus usually leads to an initial severe febrile illness in nearly everyone exposed at 1 to 6 days after exposure. Title: Treatment of Neuroterrorism\nPassage: Diseases caused by alphaviruses are mainly neurological and include Venezuelan equine encephalomyelitis and Eastern and Western equine encephalomyelitis. This disease occurs naturally in North, Central, or South America, but human illness is rare, and most infections result in nonspecific symptoms of fever, headache, and myalgia. Less than 6% of infected adults or children will develop encephalitis, however the mortality rate of those can be as high as 50 to 75% for Eastern equine encephalitis , which is the most severe of these infections, and survivors frequently have neurological sequelae .", "Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury\nPassage: Hepcidin is a \u03b2-defensin-like antimicrobial peptide that is mainly produced by the liver. Hepcidin not only shows antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and yeasts, but also functions as a principal iron regulatory hormone . Hepcidin binds to the iron export protein ferroportin and induces its internalization and degradation, which leads to decreased cellular iron export and increased intracellular iron retention . Because iron is an essential nutrient for all organisms, hepcidin also restricts the iron available to invading microbes, thereby enhancing the host defense against pathogens . Furthermore, hepcidin can modulate the lipopolysaccharide -induced acute inflammatory response via Title: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury", "Passage: Hepcidin is produced predominantly by hepatocytes. Its hepatic expression can be upregulated by iron overload and inflammation and suppressed by hypoxia and anemia . A recent study reported that hepcidin is expressed in AECs in response to interferon-\u03b3 . In the current study, an increased hepcidin level in AECs was observed during polymicrobial sepsis. Because the lung is the first vital organ that is adversely affected at the onset of sepsis , the elevated expression of hepcidin may protect the mice against lung injury. To support this hypothesis, knockdown of hepcidin in AECs exacerbated sepsisinduced lung injury . Considering that Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: Hepcidin is bound to plasma alpha-2 macroglobulin . Evidence suggests that other cells may express the hepcidin mRNA at a much lower level than the hepatocytes; the biological significance of the extra hepatic production of hepcidin remains uncertain. Plasma hepcidin is freely treated through glomeruli and in animals with normal kidney activity it quickly passes through the urine. In addition, a part of hepcidin is cleansed through degradation along with ferritin . Title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and \u03b2-defensin-2 secreted by mesenchymal stem cells", "Passage: the regulation of iron hemostasis. This peptide prevents iron absorption from the small intestine and releases iron from reticuloendothelial cells. In infectious diseases, macrophages and bacteria compete to absorb iron . Macrophages interfere with the absorption of iron by bacteria. Eventually, the pathogen does not grow and replenish. Factors that cause hepcidin production are increased in bone marrow and anemia. Other factors that increase the production of hepcidin are iron accumulation and inflammation .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Most of the analysis of MERS-CoV genetics has been performed using high throughput or \"deep\" sequencing methods for complete genome deduction . MERS-CoV was the first subject of such widespread use of deep sequencing to study an emerging viral outbreak with global reach. The technique can produce genomic . Earlier and subsequent versions of this chart are maintained on a personal blog length coverage in a single experiment with highly repetitious measurement of each nucleotide position . Despite assays having been published early on, subgenomic sequencing, once the mainstay of viral outbreak studies, has less often been published during MERS-CoV Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Analyses of MERS-CoV genomes have shown that most single nucleotide differences among variants were located in the last third of the genome , which encodes the spike protein and accessory proteins . At least nine MERS-CoV genomes contained amino acid substitutions in the receptor binding domain of the spike protein and codons 158 , 460 , 1020 , 1202 and 1208 bear investigation as markers of adaptive change . The spike protein had not changed in the recombinant MERS-CoV genome identified in China in 2015 but was reported to have varied at a higher rate than that for complete MERS-CoV Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Vigilance remains important for containment since MERS-CoV is a virus with a genetic makeup that has been observed for only three years and is not stable. Among all humans reported to be infected, nearly 40 % have died. Continued laboratory testing, sequencing, analysis, timely data sharing and clear communication are essential for such vigilance to be effective. Global alignment of case definitions would further aid accurate calculation of a case fatality ratio by including subclinical case numbers. Whole genome sequencing has been used extensively to study MERS-CoV travel and variation and although it remains a tool for experts, it appears Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC", "Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: Significance and potential impact of the study To provide greater insight into social network structures in resource poor settings, we propose to study social contact patterns within schools and households and compare and contrast patterns in the urban and rural setting exhibiting different demographic, economic, and socio-cultural characteristics. This will provide key data for use in transmission dynamic models for common respiratory viral and bacterial infections such as RSV and S. pneumoniae that are the leading cause of childhood morbidity and mortality in the SSA setting. We also seek to answer the question how we can optimize study design to Title: Quantifying the value of surveillance data for improving model predictions of lymphatic filariasis elimination", "Passage: Significance was determined using the Benjamini-Hochberg procedure for controlling the false discovery rate in all pairwise statistical tests. + information gained by each data stream are presented in comparison to the information contained in the model-only simulation Title: Temporal trends in the discovery of human viruses\nPassage: is therefore of considerable interest. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: how the characteristics of the field change over time will be interesting to see.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: algorithm . In general, SSA is employed to improve FPA to avoid its drawbacks . The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error , Root Mean Squared Relative Error , Root Mean Squared Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: This section explains the proposed FPASSA-ANFIS method. It is a time series method for forecasting the confirmed cases of the COVID-19, as given in Figure 2 . The FPASSA-ANFIS utilizes the improved FPA to train the ANFIS model by optimizing its parameters. The FPASSA-ANFIS contains five layers as the classic ANFIS model. Layer 1 contains the input variables . Whereas Layer 5 produces the forecasted values. In the learning phase, the FPASSA is used to select the best weights between Layer 4 and Layer 5. Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: This paper aims to assess the ability of the FPASSA to forecast the COVID-19 by comparing its performance with other methods, namely the ANFIS and the trained ANFIS models using PSO, GA, ABC, FPA, and FPASSA. The parameters' setting for these models is listed in Table 2 . Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: percentage of the increase over the forecasted period is 10%, the highest percentage is 12% on 28/2/2020, and the lowest percentage is 8.7% on 19/2/2020. From the previous results, it can be concluded that the proposed FPASSA-ANFIS has a high ability to forecast the COVID-19 dataset. These results avoid the limitations of traditional ANFIS because of the combination with the modified FPA method. Moreover, the operators of SSA are combined with the local strategy of FPA to enhance their exploitation ability. However, the time computational of the proposed FPASSA method still requires more improvements.", "Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016\nPassage: patients to those who were on the unit for 3 days or more. On six randomly assigned days over a 2 month period, all eligible patients on the unit had a proforma filled retrospectively for all days up until their admission to the unit, or up to seven days previously, whichever sooner. Presence of arterial or central access was also noted, as these facilitate obtaining samples. Results: We obtained 101 patient days worth of data across 20 patients who were considered eligible. Our results demonstrated that 54% of tests done were required but more importantly, 46% of tests carried out Title: Accuracy of using automated methods for detecting adverse events from electronic health record data: a research protocol", "Passage: This study will be conducted at two leading Canadian academic health centres: the McGill University Health Centre and The Ottawa Hospital . The MUHC is composed of five acute care hospitals and has more than 800 adult beds. It serves a population of 1.7 million people , with an annual volume of 735,000 ambulatory visits, 33,300 surgeries, and 40,000 hospitalizations . TOH is composed of three campuses serving a community of more than one million people across the National Capital Region and Eastern Ontario. It is composed of 1,149 beds, with annual volumes of more than 1,000,000 ambulatory care visits, Title: Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study", "Passage: Of the 200 enrolled in this study, 25 patients were excluded from the analysis of the data. Of these, 21 patients had incomplete sampling and four patients met exclusion criteria. The characteristics on admission of the 175 patients included in our analysis study group are presented in Table 1 . Mean age was 62 years; roughly one-third had CAP, one-third had HAP, and one-third had VAP. The median hospital and ICU lengths of stay prior to enrolment were six days and nine days , respectively. Title: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016", "Passage: The data from 1,000,000 National Health Insurance beneficiaries were utilized. The study cohort consisted of 42,581 diabetic patients and 672,750 unexposed subjects. Among patients with diabetes, 1082 have been admitted with hyperglycemic crisis episodes. All adult beneficiaries were followed from 1 January 2005 to 31 December 2012 to evaluate if pancreatic cancer was diagnosed. Cox regression models were applied to compare the hazards adjusted for potential confounders.", "Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome\nPassage: We previously demonstrated that the influenza virus M2 protein , its H37G mutant , and the EMCV 2B protein stimulates NLRP3 inflammasome-mediated IL-1\u03b2 secretion . In addition, the SARS-CoV E protein acts as a Ca 2+ -permeable ion channels that activates the NLRP3 inflammasome . The fact that 3a protein of SARS-CoV acts as viroporin prompted us to examine whether it also triggers inflammasome activation. Thus, we first generated lentivirus plasmids expressing V5-tagged proteins and confirmed their expression in HEK293FT cells by immunoblot analysis . We next transduced lipopolysaccharide -primed BMMs with the lentiviruses expressing the SARS-CoV E, 3a, M, Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: In summary, we found that the ion channel activity of SARS-CoV 3a protein is essential for activation of the NLRP3 inflammasome. In addition, both K + efflux and mitochondrial ROS production are required for SARS-CoV 3a-mediated IL-1\u03b2 secretion. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome\nPassage: Next, we determined the subcellular localization of the SARS-CoV 3a protein using confocal microscopy. When the SARS-CoV Cell-free supernatants were collected at 24 h or 6 h post-infection or stimulation, and analyzed for IL-1\u03b2 by ELISA. Data are representative of at least three independent experiments, and indicate the mean \u00b1 SD; * * P < 0.01 and * * * P < 0.001. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Finally, we investigated the mechanism by which SARS-CoV 3a triggers NLRP3 inflammasome activation. A previous study showed that the 3a protein of SARS-CoV acts as a K + channel . In addition, K + efflux is a well-known activator of the NLRP3 inflammasome . These observations prompted us to examine whether K + efflux is required for 3a-mediated IL-1\u03b2 secretion. To this end, BMMs in K + -rich medium were infected with influenza A virus or lentiviruses expressing the SARS-CoV E or 3a proteins. In agreement with a previous result , we found that IL-1\u03b2 secretion caused by influenza virus", "Title: Investments in respiratory infectious disease research 1997\u20132010: a systematic analysis of UK funding\nPassage: Tuberculosis also represents a substantial challenge to global health, accounting for 2.2% of all-cause DALYs lost world-wide, 1 and an estimated 1.4 million deaths in 2011. 3 The target of the WHO Global TB Plan is to reduce tuberculosis deaths to half of those recorded in 1990 by 2015, but it is thought that both Europe and Africa will fail to meet these goals. Control efforts are hampered by limited vaccine effectiveness, coinfection with HIV, insufficient diagnostic capacity in low income settings, prolonged treatment courses and the emergence of drug resistant strains. 3, 4 Globally an estimated 500,000 deaths annually Title: Investments in respiratory infectious disease research 1997\u20132010: a systematic analysis of UK funding", "Passage: 1 and an estimated 1.4 million deaths in 2011. 3 The target of the WHO Global TB Plan is to reduce tuberculosis deaths to half of those recorded in 1990 by 2015, but it is thought that both Europe and Africa will fail to meet these goals. Control efforts are hampered by limited vaccine effectiveness, co-infection with HIV, insufficient diagnostic capacity in low income settings, prolonged treatment courses and the emergence of drug resistant strains. 3, 4 Globally an estimated 500,000 deaths annually are attributable to influenza. 5 1 2 3 4 5 6 7 8 9 10 11 12 Title: Tuberculosis mortality: patient characteristics and causes", "Passage: Tuberculosis remains a serious public health issue worldwide. Even in the era of effective chemotherapy, TB still accounts for a substantial number of deaths annually. Early diagnosis is challenging, even in areas with abundant medical resources . In 2012, there were an estimated 12 million TB cases globally, including 8.6 million new cases, and 1.3 million fatal cases . The global case-fatality rates are reported to be between 7% and 35% , and risk factors for death may include noninfective comorbidities, human immunodeficiency virus infection and multidrug-resistant TB . Since the World Health Organization defined TB deaths as the number Title: Mortality among patients with tuberculosis requiring intensive care: a retrospective cohort study", "Passage: Across the world tuberculosis remains an important public health problem, especially in developing countries. One third of the world's population is infected with Mycobacterium tuberculosis. Brazil is ranking 15 th among the 22 high-burden countries that collectively account for 80% of TB cases globally. The incidence of TB was of 50 cases/100,000 population/yr in 2006, and recently reached approximately 100 cases/ 100,000 population in the city of Porto Alegre . Every year, almost 2 million people die of TB, most of them in low-and middle-income countries. The annual death rate from TB in Brazil was estimated at 4.0/100,000 population/yr in", "Title: Innate Immune Sensing and Response to Influenza\nPassage: Influenza virus-induced NLRP3-mediated IL-1b and IL-18 production involve two steps that include, enhancing the transcription of genes encoding pro-IL-1b and pro-IL-18 and NLRP3 and activating NLRP3 inflammasome . Signal 1 is initiated by the detection of viral RNA by TLR7, which activates NF-kB. Although initial studies showed that NLRP3 detects influenza virus via recognition of viral RNA , it is now clear that many sources contribute to signal 2 either in combination or alone, and all depend on the newly synthesized viral M2 protein. These include, ionic imbalance of the trans-Golgi pH, potassium efflux through the P2X7 receptor, an ATP-gated Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: The innate immune systems utilizes pattern recognition receptors to detect pathogen-associated molecular patterns . Recognition of virus infection plays an important role in limiting virus replication at the early stages of infection. Nod-like receptor family, pyrin domain-containing 3 is activated by a wide variety of stimuli, including virus infection . Four models describing activation of the NLRP3 inflammasome have been proposed thus far . First, the disturbances in intracellular ionic concentrations, including K + efflux and Ca 2+ influx, play an important role . Second, cathepsin B and L, which are specific lysosomal cysteine proteases, are though to play a Title: Innate Immune Sensing and Response to Influenza", "Passage: Studies have shown that NLRP3 , NLRC2 , and NLRX1 are the NLRs responding to influenza virus . Whereas NLRP3 inflammasome induces the secretion of mature IL-1b/IL-18, NLRC2/NOD2, and NLRX1 signals the production of type I IFNs in response to influenza virus. Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: Thus far, several models have been proposed to explain NLRP3 inflammasome activation by RNA viruses. First, viral RNA or RNA cleavage products generated by RNase L activate the NLRP3 inflammasome via the DExD/H-box helicase, DHX33 . Second, viroporins encoded by RNA viruses activates the NLRP3 inflammasome . In the case of influenza virus, the proton-selective M2 ion channel in the acidic trans-Golgi network activates the NLRP3 inflammasome . Interestingly, an M2 mutant in which histidine was substituted with glycine at position 37 , causing loss of proton selectivity, enables transport of other cations , thereby leading to enhanced secretion of", "Title: Assessing dengue control in Tokyo, 2014\nPassage: We conducted model comparisons to assess the importance of accounting for the effectiveness of the abovementioned control measures. The sensitivity results are summarized in S3 Table. It appeared that the latest estimate of the reproduction number was sensitive to the presence of effectiveness parameters . Regardless of whether the assumed number of generations was 2, 3, or 4, AICc values of the model with both \u03b5 1 and \u03b5 2 were minimal , Note: Two-generation, three-generation, and four-generation models indicated that there were a total two, three, and four generations, excluding generation zero. Mean \u03bc IP and standard deviation \u03c3 Title: Comparative Analysis of the Effectiveness of Three Immunization Strategies in Controlling Disease Outbreaks in Realistic Social Networks", "Passage: and reliable, the scenarios when R 0 varies from 2.0 to 6.0 were analyzed in the sensitivity analysis. The relevant parameters are given in Table 2 . Title: A decision-support framework to optimize border control for global outbreak mitigation\nPassage: It is therefore necessary to evaluate the effectiveness of the proposed strategies under imperfect control conditions. To explore the impact of imperfect control, we set upper bounds lower than 1 on the control rate at airports and measure performance in the base case scenarios. The outcome is reported Figure S6 . The performance of each control strategy is presented for the cases where the control rate is limited to 0.9 and 0.8. The results are compared with the perfect control scenario. We assume that the same set of airports is controlled in all simulations. Title: A decision-support framework to optimize border control for global outbreak mitigation", "Passage: The results once again highlight the robustness of the control strategies. The increase in infected cases increases as the perfect control assumption is relaxed, however the relative performance and ranking across strategies remains robust to this relaxation. We also report a more apparent increase in cases between full control and 90% control, compared with the difference in 80% and 90% control effectiveness.", "Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines\nPassage: Vaccines have always been considered as one of the most effective preventions against various types of infections, ranging from bacterial to viral infections. In fact, their effectiveness in the prevention of infectious diseases could be clearly observed in the eradication of smallpox, declared officially in 1976 by WHO, just two centuries after Edward Jenner showed the prevention of smallpox infection by inoculating cowpox into a person . Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: and targeted antiviral prophylaxis, other population-level social distancing measures such as school and workplace closures and travel restrictions are likely to be somewhat effective in reducing influenza transmission in the community , but implementation on a prolonged basis and with repeated waves of the pandemic could be difficult. Household-based quarantine and isolation will likely be effective in mitigating the impact of a pandemic . There is however considerable uncertainty about the efficacy of some non-pharmaceutical interventions at the personal level including face masks and hand hygiene. Our proposed study, to assess the efficacy of masks and hand-hygiene for influenza control, Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: Our study compared three interventions. In the control arm, households received education about the importance of a healthy diet and lifestyle, both in terms of illness prevention and symptom alleviation . Households in the face mask arm received the control intervention plus education about the potential efficacy of masks in reducing disease spread to household contacts if all parties wear masks, distribution of a box of 50 surgical masks for each household member , and demonstration of proper face-mask wearing and hygienic disposal. Index subjects and all household contacts were taught to wear masks as often as possible at home Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households\nPassage: through intensive counselling, and demonstration of proper wearing of masks or hand washing.", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: The virosphere is the most successful reservoir of biological entities on our planet in terms of numbers of particles, speed of replication, growth rates, and sequence space. There are about 10 33 viruses on our planet and they are present in every single existing species . Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: Abstract: The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution. Viruses are the most abundant biological entities on Earth. They are present everywhere, in our surrounding, the oceans, the soil and in every living being. Retroviruses contributed to about half of our genomic sequences and to the evolution of the mammalian placenta. Contemporary viruses reflect evolution ranging from the RNA world to the Title: Bioaerosols Play a Major Role in the Nasopharyngeal Microbiota Content in Agricultural Environment", "Passage: Although, Actinobacteria are most abundant in the non-exposed controls, no pathogen was identified in the most abundant taxa presented in Figure 6 . An example of the most abundant Actinobacteria in non-exposed control is Micrococcus Luteus that was differentially more abundant in controls compared to farmers. Another example of Firmicutes is Staphylococcus epidermis that was more abundant in the controls compared to the farmers. Title: Deciphering Biosignatures in Planetary Contexts", "Passage: The structural complexity of organisms appears to have increased during the biological evolution on Earth, although it is acknowledged that there are multiple criteria by which complexity can be gauged . The earliest organisms were unicellular and perhaps even preceded by acellular ones for which we have no fossil record. There was then a development from single-celled bacteria, archaea, and eucarya, to multicellular organisms. As a result of this progression, biochemical complexity has also evolved over time according to various metrics , with certain metabolic capabilities arising sequentially . It further seems logical that, however, life began, it started in", "Title: Early Days of Food and Environmental Virology\nPassage: of disposable diapers to mothers whose infants were receiving the oral polio vaccine, if the mothers would freeze and return any diapers with feces in them. Our laboratory thawed and assayed the feces. When at least 100 g of high-titer feces were accumulated, these were flushed down a toilet at a study-site home, and samples were taken from the septic tank and groundwater over time. Title: Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection", "Passage: To obtain a representative sample of the feces produced by each mouse and to minimalize sampling error, fecal samples consisted of ten fecal pellets that accumulated in the cages of single-housed mice since the previous collection. Accordingly, on the day of infection and after every fecal collection, mice were transferred to new cages with clean bedding. Mice from the cohorts to be euthanized on days 9 and 11 p.i. were analyzed. DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit into a total volume of 200 \u03bcl. Viral genome copies in 1 \u03bcl of this sample Title: Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance", "Passage: containers, which were toughly rinsed with water prior to collecting samples. From each of the individual airplanes 6-8 waste toilets were emptied under high vacuum pressure into the special container at the service car. This procedure mixes the content thoroughly and no individual fecal clumps or toilet paper can be visually identified. Three individual \u00bd L samples where then collected using sterile tubes from the cars waste container and placed in a refrigerator. Subsequently, a container was rinsed with water before collecting toilet waste from another airplane. Between one and seven flights were collected during a maximum of 12 hours Title: Early Days of Food and Environmental Virology", "Passage: We did a second sampling series that was directed especially to food processing personnel in Plant C and eight other establishments. Samples were collected from the sanitary sewer lines that served personnel toilets, either as grab samples or with swabs suspended in the line for a week. None of these was shown to contain the virus.", "Title: Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors\nPassage: Arenaviruses are enveloped, ambisense single-stranded RNA viruses. Their structure consists of a membrane envelope containing the surface glycoprotein subunits surrounding a capsid, which consists of the Z matrix protein . Inside the capsid are the L RNA-dependent RNA polymerase and the viral bi-segmented genome encapsulated by the nucleoprotein . Cell entry is mediated by GP, which is first expressed as the glycoprotein precursor complex . The host subtilase SK1-S1P proteolytically cleaves GPC into its three final subunits : GP1, GP2, and SSP , which form heterotrimers on the cell membrane surface . GP1 forms spikes protruding from the viral envelope Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: Text: The virus family Arenaviridae consists of only one genus, but most viruses within this genus can be divided into two different groups: the Old World arenaviruses and the New World arenaviruses . The differences between the two groups have been established through the use of serological assays. Most of the arenaviruses cause persistent infection in rodents without any symptoms, and humans acquire a variety of diseases when zoonotically infected. Lymphocytic choriomeningitis virus is the only arenavirus to exhibit a worldwide distribution, and causes illnesses such as meningitis . Congenital LCMV infections have also been reported . Most importantly, viral Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: Abstract: The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World and New World complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques Title: Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections", "Passage: Viruses in the family Arenaviridae have bi-segmented single-stranded RNA genomes with a characteristic organization and gene repertoire . The larger genome segment is about 7 kb in length and encodes the viral RNA-dependent RNA polymerase and a small zinc-binding RING domain protein . The smaller segment is about half as long and encodes the glycoprotein precursor and nucleoprotein . On each segment, the two viral genes are in opposite coding orientations and are separated by an intergenic region that is predicted to form stable hairpin structures.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV does not appear to be easily transmitted from DCs to humans, or perhaps it is , but generally does not trigger a detectable immune response if only mild disease or asymptomatic infection results. Serology assays are in need of further validation in this area so care is required when moving newly developed diagnostic serology algorithms from a research setting to one that informs public health decisions. This was reinforced when a false positive US case, purported to have been infected after a handshake and two face-to-face meetings, did not withstand further confirmatory analysis using a more specific, NT assay Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: disease severity in South Korea cases with most responses detectable by week three of illness while others, even though disease was severe, did not respond for four or more weeks . The implications for our ability to detect any response in mild or asymptomatic cases was not explored but may be a signifcant factor in understanding exposure in the wider community. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: for human sero-surveys. These relied on MERS-CoV-infected cell culture as an antigen source, detecting the presence of human anti-MERS-CoV IgG, IgM or neutralizing antibodies in human samples . No sign of MERS-CoV antibodies was found among 2,400 sera from patients visiting Hospital in Jeddah, from 2010 through 2012, prior to the description of MERS-CoV . Nor did IFA methods detect any sign of prior MERS-CoV infection among a small sample of 130 healthy blood donors from another Hospital in Jeddah . Of 226 slaughterhouse workers, only eight were positive by IFA, and those sera could not be confirmed by virus Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Although DCs appear to suffer the equivalent of a 'common cold' from MERS-CoV infection, in humans, the virus can be a more serious and opportunistic pathogen associated with the death of up to 40 % of reported cases. It has yet to be established whether infections thought to have been acquired from an animal source produce a more severe outcome than those spread between humans . Studies have established that the mean incubation period for MERS is five to six days, ranging from two to 16 days, with 13 to 14 days between when illness begins in one person and", "Title: Viral vector-based influenza vaccines\nPassage: In the future, more novel vector-based influenza candidate vaccines will be developed and tested in clinical trials. There is potential for improvement by the modification of viral antigens, like the 'headless' or 'shielded' HA constructs, to broaden the reactivity of vaccine induced antibodies. In addition to modifying influenza virus antigens, post-translational modifications and modifications to promoter sequences could also alter and improve the immunogenicity. 226, 227 The biggest challenge of taking vector-based vaccines to the market may be obtaining approval from the regulatory authorities. Only when their safety and superiority over existing vaccine formulations have been demonstrated, implementation of these Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Based on the most recent MERS-CoV outbreak, there are already a number of vaccine candidates being developed but most are still in the preclinical testing stage. The vaccines in development include viral vector-based vaccine, DNA vaccine, subunit vaccine, virus-like particles -based vaccine, inactivated whole-virus vaccine and live attenuated vaccine. The latest findings for these vaccines arebased on the review by Yong et al. in August 2019 . As of the date of reporting, there is only one published clinical study on the MERS-CoV vaccine by GeneOne Life Science & Inovio Pharmaceuticals . There was one SARS vaccine trial conducted by Title: Vaccines for the future: learning from human immunology", "Passage: Traditional vaccines based on inactivated or attenuated pathogens or on purified pathogen subunits, such as toxins, proteins and polysaccharides, have been very efficient in preventing infections of pathogens with low degree of antigen variability. These vaccines work mainly by eliciting functional antibodies that can neutralize viral invasion, neutralize bacterial toxins and induce opsono-phagocytosis or complement-mediated killing of bacteria . It has also been possible to develop effective vaccines to prevent pathogens that have a moderate degree of antigen variability and exist in multiple strains. The problem has been solved by developing multivalent vaccines, which combine multiple antigens, each directed against Title: Vaccines for the future: learning from human immunology", "Passage: vaccinated with the Yellow fever vaccine YF-17D . These studies have shown that it is possible to predict the efficacy of the vaccine by measuring the transcriptome of PBMCs few hours after vaccination. Interestingly, the predictive innate immune signatures were not obvious, involving genes, such as EIF2AKA that had not been associated with the generation of adaptive responses before. The new biological information discovered by systems biology approaches helped to better understand the mechanism of action of the vaccine and can now be exploited to rationally design improved vaccine adjuvants targeting the 'protective' genes or pathways .", "Title: Estimating the number of infections and the impact of non-\nPassage: to the infection fatality ratio. Title: Estimation in emerging epidemics: biases and remedies\nPassage: Another useful application of the above result is to countbased estimation of the case fatality rate . In this case, p represents the probability of dying from the disease. The problem has been treated by many authors under many different assumptions of data availability ). It is well known that a crude estimator of the type D/N, D denoting number of dead individuals and N number of notified individuals in , will underestimate the 'true' CFR. In theory, disregarding biased reporting, the underestimation is reflected in the integral part of equation , which is always less than 1, where h Title: Estimating the number of infections and the impact of non-\nPassage: influence the rate of death and hence the estimated number of true underlying cases. Title: Estimating the number of infections and the impact of non-", "Passage: 19 infection-fatality-ratio ifr 9 together with a distribution oftimes", "Title: Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus\nPassage: The question is to what extent these results are influenced by the composition of vaccines from different manufacturers and to what extent different types of vaccines . There was an obvious difference in the quality between the inactivated vaccines, whereas the character of the immune response to both MLV vaccines was similar with only partial differences in the time-related response dynamics. The vaccine B3 showed a more pronounced decrease in virus secretion and a tendency to induce sterile immunity, while B4 vaccine had a more pronounced of CMI in lymphocyte transformation test. It should be noted that the strain used Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies", "Passage: The unpaired Student's t-test was used to determine if the differences in influenza-specific responses observed between groups of mice were significant. A p value of p < 0.05 was considered significant. Spearman correlation analysis was performed to assess the relationship observed between serum and mucosal influenza-specific IgG responses. Title: Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus", "Passage: Cell-mediated immune response after challenge infection was positive in all vaccinated groups and in the control group after 21 days post infection, using ELISpot in PBMC from bronchoalveolar lavages. The results were recalculated to the number of CD3 + lymphocytes. The differences between individual animals, but no significant differences between groups were detected . Title: A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence\nPassage: Finally, we tested further signature cytokines for different Th immune responses, bovine Interferon gamma and Interleukin 4 , to analyze differentiation of T helper subsets. We detected no significant differences between lymphocytes of vaccinated and unvaccinated controls and BNP cases after IFN\u03b3 or IL-4 stimulation in vitro . This proves a crucial role for IL-2 in the deviant immune responses, but not for IFN\u03b3 or IL-4.", "Title: Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies\nPassage: Despite the advantage of mucosal immunization for the induction of SIgA responses, the mucosal route is suboptimal for the induction of systemic antibody responses . In case of influenza, systemic antibodies are important since they contribute to protection against virus replication in the lungs and are the only correlate of protection so far recognized by regulatory authorities . Furthermore, due to the default Th2oriented nature of mucosal immunity, mucosal immunization shows limited induction of Th1-related antibody subtypes , which are preferable for viral clearance . Title: The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human", "Passage: The stability of the mucus barrier and the innate defense mechanisms rely on the secretion of intact, gel forming mucus and the availability of mucosal immune proteins, including immunoglobulins and the trefoil factor peptides. Together these factors normally ensure mucosal cell integrity and epithelial homeostasis through restitution and regeneration processes. Part of the risk is linked to the immature state of the mucosa at this very early stage of life. A role for the mucins in the pathogenesis of NEC is indicated by the depletion of Goblet cells seen in the mucosa of neonates with NEC and this is expected Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: of both innate and adaptive immunities with an IL-23/T H 17 phenotype. 28, 29 Immune-regulated alterations in mucin glycosylation following Trichuris muris infection contribute to clearance of parasitic infection. 30 Besides mucin secretion, a new underappreciated role of goblet cells is antigen sampling through the goblet cellassociated antigen passages under homeostatic conditions. 31 Overriding GC microbial sensing to open colonic GAPs or inappropriate delivery of luminal pathogens through GAPs resulted in the influx of leucocytes and the production of inflammatory cytokines in the setting of normal, non-pathogenic, microbiota. 31, 32 This microbial sensing by colonic GCs has a critical role Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: As discussed, cytokines such as IL-4, IL-13 and IL-10 can boost protein production in mucin-secreting goblet cells. 54, 75, 76 There are several reports of correlations of cytokine levels with disease; however, limited research has been done on the direct effect of cytokines on protein biosynthesis.", "Title: Alpha-COPI Coatomer Protein Is Required for Rough Endoplasmic Reticulum Whorl Formation in Mosquito Midgut Epithelial Cells\nPassage: at 10000 rpm for 10 min at 4uC. The supernatant was transferred to a pre-chilled 1.5-ml tube and 56SDS sample loading buffer was added. The mixture was boiled for 4 min, chilled on ice for 2 min, and then spun at 13000 rpm for 5 min at room temperature. The yielded supernatant was stored at 220uC for SDS-PAGE. Title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice\nPassage: of 92 \u00b0C for 1 min, 58 \u00b0C for 1 min and 72 \u00b0C for 2 min; followed by final elongation at 72 \u00b0C for 10 min. Title: Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells", "Passage: Tubulin polymerization assay was performed essentially as previously described . Briefly, cells grown to confluency in 24-well plates were washed twice with 1X PBS. To separate polymerized from soluble tubulin, the cells were all incubated at 37uC for 5 min in the dark in hypotonic lysis buffer containing 5 mM paclitaxel, 10 mM Trichostatin-A , 1 mM MgCl2, 2 mM EGTA, 0.5% Nonidet P-40, 2 mM phenylmethylsulfonyl fluoride, 200 units/ml aprotinin, 100 mg/ml soybean trypsin inhibitor, 5.0 mM e-amino caproic acid, 1 mM benzamidine, and 20 mM Tris-HCl, pH 6.8, vortexed vigorously and centrifuged at ,15,000 g at 22uC for Title: Tollip or Not Tollip: What Are the Evolving Questions behind It?", "Passage: The average length of Tollip was 262 amino acids with a standard deviation of 64 amino acids; and the molecular weight average was 31.33 kDa with a standard deviation of 6.78 kDa. Through splits decomposition and analysis of alignment, after block curing, we could estimate the proportion of invariant sites as 68.54% and the segregant sites counted was 77 in amino acid base. These findings suggest a tendency of recurrent duplications and/ or insertions, as well as deletions evidenced by variations in the length and mass of protein ranging between approximately 25% and 4.62 fold, respectively. But it is important", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Proximity to water bodies increases the risk of outbreaks , possibly by increasing the chance of contact between wild water birds and domestic poultry. We measured the distance between the commune and the nearest: a) lake and b) river. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: Proximity to water bodies increases the risk of outbreaks , possibly by increasing the chance of contact between wild water birds and domestic poultry. We measured the distance between the commune and the nearest: a) lake and b) river. Title: Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak", "Passage: analysis revealed that HPAI spread among Minnesota poultry premises was heavily distance-dependent during the 2015 outbreak . Our results support this claim by providing evidence that the frequency of viral transition between two locations increases as the distance between locations decreases. Risk of infection due to proximity can also be observed in our discrete trait diffusion model in which withinstate HPAI spread was much more frequent than inter-state spread. HPAI movement between states may explain Bonney, et al.'s finding that distance-independent transmissions significantly improved the fit of their transmission kernel model . Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: distances to the highway junction , and a high density of roads in a subdistrict. Moreover, the HPAI risk decreased when the distance radius to major cities increased. To a lesser extent, a very short distance to the closest highway was also associated significantly with a higher HPAI risk for chickens and ducks.", "Title: Viral vector-based influenza vaccines\nPassage: Alphaviruses are single-stranded RNA viruses with a positive sense genome of the Togaviridae family. Several alphaviruses are being developed as vaccine vectors, including semliki forest virus , sindbis virus and Venezuelan equine encephalitis . These vectors often are replication deficient replicons that do not encode viral structural proteins, as these regions of the genome are replaced by transgenes of interest. Viral RNAs are self-replicating and are capable of transgene expression at high levels. 98 As an added advantage, when using alphavirus replicons pre-existing immunity to the vector should not pose a problem and multiple sequential vaccinations are a possibility. Furthermore, Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Alphaviruses are positive-sense, single-stranded RNA viruses of the Togaviridae family. A variety of alphaviruses have been developed as vaccine vectors, including Semliki Forest virus , Sindbis virus, Venezuelan equine encephalitis virus, as well as chimeric viruses incorporating portions of SIN and VEE viruses. The replication defective vaccines or replicons do not encode viral structural proteins, having these portions of the genome replaces with transgenic material. Title: Viral vector-based influenza vaccines", "Passage: to HVT, was shown to be an effective vaccine vector against A virus and even performed better than HVT in a side-by-side comparison in chickens. 127 Pseudorabiesvirus is an alphaherpesvirus of pigs and attenuated strains of PrV have been generated and used for control of Aujeszky's disease in pigs. 128 expressing HA from a swine A virus was tested in mice and induced protective immunity against infection with heterologous A virus. 131 An attenuated strain of equine herpesvirus , an alphaherpesvirus that infects horses, has an impressive safety record in horses and other mammalian species and therefore should be considered Title: Viral vector-based influenza vaccines", "Passage: Another alphaherpesvirus of poultry, turkey herpesvirus has also been extensively studied as influenza vaccine vector in chickens. HVT encoding the HA gene of an A virus afforded protection from infection with various A viruses. Similarly, a recombinant HVT-H7 vaccine protected chickens against infection with the homologous A virus. 125 Since chickens are often vaccinated at very young age , maternal antibodies against the vector or against the protein encoded by the transgene could influence vaccine efficacy. Interestingly, HVT was shown to be immunogenic even in the presence of these maternal antibodies. 126 Marek's disease virus , an alphaherpesvirus closely related", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: The radiology department was divided into four areas : contaminated, semicontaminated, Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Figure 1. Diagram of the layout of our radiology department was divided into four areas: contaminated Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: Reconfiguration of the radiology department Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: The radiology department has 65 diagnostic radiologists and 161 other staff members", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Hantavirus diseases of man have long been suspected of having an immunopathogenic basis in part because of their relatively long incubation period of 2-3 weeks and the observed temporal association between immunologic derangements and the first appearance of signs and symptoms of hantavirus illness. HFRS and HCPS share many clinical features, leading many investigators to consider them to be, in essence, different manifestations of a similar pathogenic process, differing mainly in the primary target organs of disease expression . The pathogenesis of hantavirus infections is the topic of a continuously-updated review in the series UpToDate . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: The ANDV-Syrian hamster model has a number of features in common with the human disease, as well as some differences. Unlike the neurologic diseases that have been possible to elicit with HTNV, the hamster model for HCPS appears to be caused by capillary leak that results in pulmonary edema and the production of a pleural effusion with exudative characteristics. Typically the hamsters die between 11 and 14-d post-inoculation, reflecting a slightly accelerated incubation period in comparison to human infections. As with human HCPS, the microscopic examination of the lung reveals abundant fibrin deposition, thickened alveolar septa, and viral antigen expressed Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Human infection by hantaviruses is thought to follow contact with secretions or excretions produced by infected rodents. In the United States, 538 human infections by hantavirus were reported through late December 2009 , with New Mexico, Arizona and Colorado exhibiting the highest case-loads. While the prototypical central American hantavirus in central America was Rio Segundo virus of Reithrodontomys mexicanus from Costa Rica, the first human disease appeared some years later in Panama, where Choclo virus arose as the etiologic agent and is believed to be responsible for all known cases of HCPS. The fulvous pygmy rice rat Oligoryzomys fulvescens has Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: The protracted incubation period associated with hantavirus disease gives the host considerable time to mount a mature immune response against the virus. Thus, in contradistinction to infections of comparable severity and related symptomatology associated with arenaviruses and filoviruses, hantavirus infections of humans are associated with antibody responses of significant titer by the time symptoms commence. Despite this observation, it appears to be possible that natural variation in individual neutralizing antibody responses among patients with SNV infections can be linked to disease severity, suggesting that administration of antiviral antibodies could prove effective therapeutically . In the case of ANDV infection, new", "Title: Estimating the number of infections and the impact of non-\nPassage: deaths . To maximise the ability to observe intervention impact Title: Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology\nPassage: key uncertainty limiting the design of optimal interventions. For non-selective campaigns, a larger age-range should increase the chances of reaching non-immune individuals; however, it should also result in more resources spent on vaccinating those already immune and necessarily increases the time to implement a campaign. The delay in the completion of vaccination could limit the potential impact of a campaign and the ability to rapidly respond elsewhere if an outbreak spreads . Title: A Statistical Framework for the Adaptive Management of Epidemiological Interventions", "Passage: A key challenge to calculating optimal intervention strategies involves devising ways to characterize and explore the space of intervention policies. Most existing work on optimal intervention has required various limiting assumptions about the forms of such strategies. Ball and Lyne considered optimal vaccination in terms of the allocation of vaccine doses to households of various sizes in an explicitly structured population model. Patel et al considered optimal vaccination in terms of the allocation of vaccine doses to different age classes in an explicitly age-and geographically-structured population model. Tildesley et al describe optimal vaccination strategies for a foot-and-mouth epidemic in which Title: Improving health aid for a better planet: The planning, monitoring and evaluation tool (PLANET)", "Passage: The second type of available information is economic and focuses largely on cost-effectiveness. Policy makers at the national and sub-national level have limited resources for scaling up cost-effective health interventions in their populations . When planning the \"best buys\" for committing their resources, they are faced with a complex task. They need to choose among at least several dozen interventions that target various diseases and vulnerable populations and decide on the most rational way to invest in the scale up of selected health interventions. Health investors usually like to know how many deaths could be averted for a fixed level", "Title: A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer\nPassage: Phage display biopanning procedures CL1-5 cells were first incubated with UV-treated inactive control helper phage . The phage-displayed peptide library , which initially contained 5610 10 plaque-forming units , was then added. The bound phages were eluted with a lysis buffer on ice. This eluted phage pool was amplified and titered in an Escherichia coli ER2738 culture . Recovered phages were used as input for the next round of panning as described previously . Title: A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer", "Passage: Ninty-six-well ELISA plates were seeded with either cancer or control cells. Individual phage particles were added to the cell-coated plates and incubated, followed by incubation with horseradish peroxidase -conjugated mouse anti-M13 monoclonal antibody and subsequently with the peroxidase substrate ophenylenediamine dihydrochloride . The reaction was stopped and absorbance was measured at 490 nm using an ELISA reader. The selected phage clones were further analyzed using DNA sequencing. The sequencing was performed with the primer 59-CCCTCATAGTTAGCGTAACG-39 corresponding to the pIII gene sequence. The phage-displayed peptide sequences were translated and aligned using GCG program. Title: A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer", "Passage: To investigate the targeting ability of the PC5-2 phage in vivo, we injected phages into the tail vein of mice bearing CL1-5-derived tumors and then recovered them after perfusion. We determined the titers of the phage in tumor masses and normal control organs . PC5-2 showed specific homing to tumor masses with concentrations 15-fold higher than its concentration in the control organs . Control helper phages did not show any specific targeting to tumor tissues . Title: A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer", "Passage: We used a phage-displayed random peptide library to isolate phages that were able to bind to NSCLC CL1-5 cells. After five rounds of affinity selection with CL1-5, cells increased the titer of phage by 40-fold . Enriched phages from the third to the fifth biopanning rounds were randomly selected. We then sequenced the phage clones with higher CL1-5binding activities. Using the Genetics Computer Group software analysis, we found that these selected phages displayed the consensus motif, tryptophan -threonine /tyrosine -tyrosine . Interestingly, the phage PC5-2 appeared in the third , fourth and fifth biopanning rounds. During the biopanning rounds, the", "Title: Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist\nPassage: Data are expressed as mean \u00b1 SD . Statistical difference between groups was determined using the unpaired two-tailed t test. When there were more than two groups, differences were analyzed using analysis of variance if the variances were equal, and the Mann-Whitney nonparametric test if variances were unequal . Linear regressions were calculated using a statistical computer package, Number Cruncher Statistical Systems . A value of P < 0.05 was considered statistically significant. Title: Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist\nPassage: relative luciferase activity of the stimulated cells divided by the relative luciferase activity of the mock cells. The assays were repeated three times independently. Title: Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist", "Passage: F2 and F3 using PCR methods, respectively, resulting in Fa and Fb fragments. These two fragments were then ligased with pcDNA3.1-V5/HisB vector. The sequence of hTLR5 in pcDNA3.1-V5/HisB recombinant was confirmed by restriction digestion and sequencing . The pcDNA3.1-V5/HisB-hTLR5 construct was transfected into HEK293T cells using Lipofectamine TM 2000 reagent, and the expressed target protein of hTLR5 was verified by western blotting. Title: Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist", "Passage: determined using BCA Protein Assay kit . Protein extracts in 30 \u00b5l of 2 \u00d7 sodium dodecyl sulfate polyacrylamide gel electrophoresis sample buffer were boiled for 10 min. Samples were separated on SDS-PAGE gel and transferred to a polyvinylidene difluoride membrane. Blots were incubated with V5 antibody . After washing three times in 1 \u00d7 TBS-T buffer, blots were subsequently incubated with goat-anti-rabbit-HRP . Antibody-antigen reactions were detected using Western Lighting Plus-ECL chemiluminescence reagents .", "Title: One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor\nPassage: Looking forward, we need to understand how NTCP interacts with both HBV envelope proteins and with other cellular proteins, especially through the motif embedded in the cell membrane. NTCP itself is not sufficient to allow HBV infection, as the majority of HepaRG cells were found to express NPCT but not to be infected . NTCP might initiate or mediate molecular interactions that can overcome the cell-surface restrictions for viral entry. Such cooperative cellular or viral factors have to be discovered and demonstrated to enhance the efficiency of viral infection, at a level comparable to a natural one . For example, Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide", "Passage: other auxiliary transporters, such as OATP, may compensate when NTCP is absent . Although these reports hint that transient downregulation of NTCP might not induce immediate adverse effects on the liver, the effect should be further investigated in in vivo models to determine whether NTCP inhibition is a reasonable anti-HBV drug target. Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide", "Passage: In this study, we generated iNTCP cells, which have high NTCP expression and high susceptibility to HBV infection, and also developed a monoclonal antibody that recognizes cell-surface NTCP. Using these tools, we identified glabridin as a compound that inhibits HBV infection by downregulating levels of its entry receptor, NTCP. Although primary hepatocytes express NTCP at low levels for the uptake of bile acids, endogenous NTCP in hepatocellular carcinoma cell lines is not sufficient to achieve successful infection with HBV in vitro. Hepatocellular carcinoma cell lines stably expressing NTCP have been created, and exhibited increased susceptibility to HBV infection , but Title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", "Passage: We next compared the efficiency of HBV infection in HepG2-hNTCP cells with that in PHHs. As shown by intracellular staining of HBV core antigen on day 8 post-infection, about 10% HepG2-NTCP cells were infected at multiplicities of genome equivalents of 100, which is comparable to the efficiency of HBV infection of PHHs . In contrast to PHHs, HepG2-NTCP cells propagate in cultures, thus the actual infection efficiency of HepG2-NTCP cells may be more likely than not underestimated by the observed end-point HBcAg staining. We also compared the levels of secreted HBeAg and intracellular viral RNAs in these two types of", "Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings\nPassage: for each ASSUR radial data point were equally weighted and the averaged data within each plot was calculated as compared to optimal ASSUR plot values of 1.0 . The developers were ranked for each of the three sample panels and overall via the average of the pooled values for both targets per sample panel and for all six targets for overall. The developers were ranked in ascending order. The ranking of the developers based upon sensitivity and specificity only is provided in parentheses; FLU, influenza A, MTB, M. tuberculosis; SP, sputum; MS2, male specific bacteriophage; SPN, S. pneumoniae; BL, blood, Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings", "Passage: ASSUR calculated each plot were equally weighted and the average of these parameters were calculated for each target microbe. These averages were then pooled and re-averaged based on the sample type and also for all three sample types and these values used to rank developers in terms of ASSUR. Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings", "Passage: based detection from the NA extracts as compared to reference methods using the MagNaPure or Qiagen kits . While important, analytical performance is not the only metric that should be considered when ranking the technologies. We also applied the ASSUR criteria defined in the Results section in a series of Radar plots to visually compare each technology with each sample type assessed for both target microbes . The normalized parameters in each panel were average by panel and also overall to permit ranking of each technology in comparison to simply performance . Title: Selection of key recommendations for quality indicators describing good quality outbreak response\nPassage: who were asked to judge appropriateness.", "Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus\nPassage: CD40L plays a critical role in orchestrating immune responses against pathogens. Depending on the post-translational modification, the murine CD40L is a 32-39 kDa type II membrane glycoprotein that was initially identified as a surface marker exclusive to activated CD4 + T cells . It is a member of the TNF superfamily consisting of a sandwiched extracellular structure composed of a \u03b2-sheet, \u03b1-helix loop, and a \u03b2-sheet, allowing for the trimerization of CD40L, an additional feature of the TNF family of ligands . Since its initial discovery, CD40L has been shown to be not only expressed on CD4+ T cells, but Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: CD40L plays a critical role in orchestrating immune responses against pathogens. Depending on the post-translational modification, the murine CD40L is a 32-39 kDa type II membrane glycoprotein that was initially identified as a surface marker exclusive to activated CD4 + T cells . It is a member of the TNF superfamily consisting of a sandwiched extracellular structure composed of a \u03b2-sheet, \u03b1-helix loop, and a \u03b2-sheet, allowing for the trimerization of CD40L, an additional feature of the TNF family of ligands . Since its initial discovery, CD40L has been shown to be not only expressed on CD4+ T cells, but Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: hetero-trimeric complexes and bind one elongated receptor molecule along each of three clefts formed by neighboring monomers of the trimer and ligand trimerization is for receptor binding . All seven known conserved residues that constitute the trimer interface on the conserved TNF domain , were mapped to the putative crCD40L protein sequence. Additionally, all six known conserved receptor binding sites on the conserved TNF domain , were mapped to the crCD40L protein sequence. Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: hetero-trimeric complexes and bind one elongated receptor molecule along each of three clefts formed by neighboring monomers of the trimer and ligand trimerization is for receptor binding . All seven known conserved residues that constitute the trimer interface on the conserved TNF domain , were mapped to the putative crCD40L protein sequence. Additionally, all six known conserved receptor binding sites on the conserved TNF domain , were mapped to the crCD40L protein sequence.", "Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features\nPassage: The incubation period of H5N1 infection in humans has usually ranged from 2-5 days, though clinical features have appeared even up to 8-17 days after exposure . Almost all patients present with high grade fever . Cough and dyspnea are seen commonly . Sore throat is seen in around half the patients with rhinitis and upper respiratory symptoms being less common. Headache, myalgia and weakness have also been reported. Gastrointestinal symptoms such as diarrhea, vomiting and abdominal pain may also be present. Watery diarrhea may precede respiratory symptoms by a week . One case with fever, diarrhea, seizure and coma Title: Clinical review: Update of avian influenza A infections in humans", "Passage: The clinical manifestations of avian influenza in humans has ranged from mild conjunctivitis to severe pneumonia with multi-organ system failure . However, with HPAI in Hong Kong in 1997 and in Southeast Asia currently, pneumonia progressing to multiorgan failure, acute respiratory distress syndrome , and death are the predominant findings . Rye syndrome, pulmonary hemorrhage, and predominant nausea, vomiting, and diarrhea complicate these cases . Laboratory findings include both thrombocytopenia and lymphopenia . Chest radiographic findings include interstitial infiltrates, lobar consolidation, and air bronchograms. The clinical course of patients with HPAI H5N1 is rapid, with 68% percent of patients developing Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features", "Passage: H1N1 most commonly causes a mild respiratory illness with fever, cough, sore throat, dyspnea, rhinorrhea, myalgias, chills, headache and fatigue. Diarrhea and vomiting are more commonly seen than with seasonal fl u. In a study of patients from April to June 2009 in the USA, gastrointestinal symptoms were seen in 39% patients . Fever and cough are the most common features seen in 93% and 83% respectively . Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features", "Passage: In 2005, 98 human cases with 43 mortalities were reported from Cambodia, China, Indonesia, Thailand and Vietnam. Again all these outbreaks were associated with an ongoing H5N1 infection in poultry. The next year the cases and geographical area increased and 115 cases with 79 deaths were reported from China, Cambodia, Azerbaijan, Djibouti, Egypt, Indonesia, Iraq, Thailand and Turkey. Most of these were again from contact with dead or live infected poultry. The only evidence of human to human transmission was in a family cluster of 8 in Indonesia in which 7 individuals died .", "Title: Oral Immunization against PEDV with Recombinant Lactobacillus casei Expressing Dendritic Cell-Targeting Peptide Fusing COE Protein of PEDV in Piglets\nPassage: T-helper cells were counted to determine the type of immune responses modulated by oral vaccination after PEDV infection. As shown in Figure 7 , the percentage of Th1 cells induced by pPG-COE-DCpep/L393, which had a significantly higher compared with Th2 cells. Compared with the percentage of Th1 and Th2, the percentage of Th1 cells in all groups was significantly higher than Th2 cells . The predominant phenotype of T cells mediated by PEDV infection is therefore a Th1 phenotype. mainly detected in villous epithelial cells. We found that the viral antigens of the PBS group in the jejunum were more Title: Oral Immunization against PEDV with Recombinant Lactobacillus casei Expressing Dendritic Cell-Targeting Peptide Fusing COE Protein of PEDV in Piglets", "Passage: T-helper cells were counted to determine the type of immune responses modulated by oral vaccination after PEDV infection. As shown in Figure 7 , the percentage of Th1 cells induced by pPG-COE-DCpep/L393, which had a significantly higher compared with Th2 cells. Compared with the percentage of Th1 and Th2, the percentage of Th1 cells in all groups was significantly higher than Th2 cells . The predominant phenotype of T cells mediated by PEDV infection is therefore a Th1 phenotype. Title: Oral Immunization against PEDV with Recombinant Lactobacillus casei Expressing Dendritic Cell-Targeting Peptide Fusing COE Protein of PEDV in Piglets", "Passage: T-helper cells were counted to determine the type of immune responses modulated by oral vaccination after PEDV infection. As shown in Figure 7 , the percentage of Th1 cells induced by pPG-COE-DCpep/L393, which had a significantly higher compared with Th2 cells. Compared with the percentage of Th1 and Th2, the percentage of Th1 cells in all groups was significantly higher than Th2 cells . The predominant phenotype of T cells mediated by PEDV infection is therefore a Th1 phenotype. Title: Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection", "Passage: endothelial cell marker CD31, as well as with a cocktail of PE labeleled antibodies specific to the following cell types : macrophages, granulocytes, CD8 + T lymphocytes, CD4 + T lymphocytes, and B lymphocytes. CD31 positive cells were enriched from total lung cells and then finally depleted of cells stained with the PE cocktail. Flow cytometric analysis of lung cell separation following in vivo infection was performed on total lung cells and PE depleted/ CD31+ enriched cells. Left and middle panels show representative data from an infected mouse . Gates were set on unstained cells, and data are representative of", "Title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus\nPassage: The development of protective humoral immunity, after vaccination or exposure to a pathogen, is dependent upon two lines of defense. The first immune defense is secreted antibodies, first from short-lived and then from long-lived, plasma cells residing somewhere in the body . The second line of defense is memory B cells . Memory cells are sentinels against reinfection which are activated upon antigen recognition to proliferate and differentiate into antibody secreting plasma cells, thus rapidly boosting circulating antibody titers with high affinity class switched antibodies . antibody repertoire development in the fetus, as the germ-free status of the pigs removes Title: Immunosenescence in vertebrates and invertebrates", "Passage: necessary to keep the cells constantly turning over; hence memory T cells can persist for a lifetime, long after antigen exposure, even in the absence of persistent infection or periodic re-infection. Turnover may be supported by cytokines released by other cells reacting to completely different antigens . Thus, T-cell clonal exhaustion could be said to be an intrinsic characteristic of adaptive immunity, continuing even in the absence of specific chronic infection. However, in natural human populations, and even in sanitized Western societies, certain chronic infections or some other infections are always likely to be present. In every country studied so Title: Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires\nPassage: switch to IgA upon T-dependent or independent signals . Sustained Ag presence could drive a protective IgA response and could be utilized to improve oral vaccines. Title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus", "Passage: of exposure to microflora . The development of protective humoral immunity, after vaccination or exposure to a pathogen, is dependent upon two lines of defense. The first immune defense is secreted antibodies, first from short-lived and then from long-lived, plasma cells residing somewhere in the body . The second line of defense is memory B cells . Memory cells are sentinels against reinfection which are activated upon antigen recognition to proliferate and differentiate into antibody secreting plasma cells, thus rapidly boosting circulating antibody titers with high affinity class switched antibodies . Currently, there is scant research on the memory B", "Title: Estimating the number of infections and the impact of non-\nPassage: Denmark 1.1% Title: Estimating the number of infections and the impact of non-\nPassage: 26. Wikipedia. 2020 coronavirus pandemic in Denmark. Wikimedia Foundation Title: Estimating the number of infections and the impact of non-\nPassage: Denmark measures cough or fever.29 12/3/2020 Title: Estimating the number of infections and the impact of non-\nPassage: https://en.wikipedia.org/wiki/2020_coronavirus_pandemic_in_Denmark.", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Like SARS-CoV, 2019-nCoV induced pneumonia through respiratory tract by clinical observation. Therefore, the presence of viral antigen in oral swabs was used as detection standard for 2019-nCoV. Similarly, two times of oral swabs negative in a 24-h interval was considered as viral clearance by patients officially. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: In the first investigation, we aimed to test whether viral positive can be found in anal swab and blood as well as oral swabs. We conducted a molecular investigation to patients in Wuhan pulmonary hospital, who were detected as oral swabs positive for 2019-nCoV upon admission. We collected blood, oral swabs and anal swabs for 2019-nCoV qPCR test using previously established method . Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "Passage: Unfortunately, in our study, we did not collect stool samples from patients and did not pursue viral RNA in the stool. But we believe the existence of virus RNA in the stool samples from these patients because that a large amount of viral RNA was detected in anal swabs and that viral RNA had also been detected in a case reported from the United States . Also, we didn't collect sputum and bronchoalveolar lavage fluid for virus detection because that the dry coughing characteristic of patients infected with 2019-nCoV prevents producing enough amount of sputum and that bronchoalveolar lavage fluid Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: through routine surveillance, and thus pose a threat to other people. In contrast, we found viral antibodies in near all patients, indicating serology should be considered for 2019-nCoV epidemiology. A possible shift from oral positive during early infection to anal swab positive during late infection can be observed. This observation implied that we cannot discharge a patient purely based on oral swabs negative, who may still shed the virus by oral-fecal route. Above all, we strongly suggest using viral IgM and IgG serological test to confirm an infection, considering the unreliable results from oral swabs detection.", "Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis\nPassage: The low availability of sequence data from influenza viruses circulating in humans, swine, or birds at the time of the 1918, 1957, or 1968 pandemics makes it difficult to conclusively rule out a role for swine. However, the sequence data available from the earliest human samples of 1918 H1N1 viruses, 1957 H2N2 viruses, and 1968 H3N2 viruses indicate that all 3 pandemic viruses have segments almost entirely avianlike in their nucleotide composition . The low uracil content of the 1918 virus does not preclude the possibility that a pandemic virus circulated in pigs briefly before transmitting to humans, but it Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: coincidence if not suggesting a close relation between the two conditions\" . Confirmation that influenza was circulating in US swine was achieved in 1931 when Richard Shope isolated the first influenza virus from pigs . Two years later, the H1N1 virus was isolated from humans . It was later demonstrated that sera from humans infected with the 1918 pandemic virus could neutralize the swine virus . Title: 1918 Influenza: the Mother of All Pandemics\nPassage: Because the only 1918 pandemic Virus samples we have Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: The simultaneous outbreaks of influenza in humans and pigs during the 1918 pandemic naturally raised questions about whether the virus had transmitted from pigs to humans, or humans to pigs. At the time, Koen noted that the flu outbreaks appeared to represent a novel disease in pigs, whereas humans had a long history of influenza pandemics, which suggested that humanto-swine transmission was more likely. Almost a century later, the reconstruction of a 1918 virus from human tissues preserved in Alaskan permafrost and autopsy blocks indicated that the virus's genes appeared to have avian origins . But this did not end", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: . The massive cell death induced may result in worsening of the acute exacerbation due to the release of their cellular content into the airway, further evoking an inflammatory response in the airway . Moreover, the destruction of the epithelial barrier may cause further contact with other pathogens and allergens in the airway which may then prolong exacerbations or results in new exacerbations. Epithelial destruction may also promote further epithelial remodeling during its regeneration as viral infection induces the expression of remodeling genes such as MMPs and growth factors . Infections that cause massive destruction of the epithelium, such as Title: Tight junctions in pulmonary epithelia during lung inflammation", "Passage: Breakdown of airway epithelial barrier function is a diagnostic marker for respiratory distress syndrome and lung injury . It indicates TJ breakdown to be causative in developing this lifethreatening lung failure. Inflammation is a major factor, which predisposes patients to lung injury and respiratory distress syndrome .However, experiments inknockout mice for several tight junction proteins revealed that those animals developed only mild lung phenotypes but they showed an increased susceptibility for lung injury . Besides barrier function, decreased fluid resorption across the airway epithelium is an additional susceptibility factor for lung injury and respiratory distress syndrome and worsens the clinical Title: Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation", "Passage: Airway epithelium represents a well-investigated target for environmental pollutants such as PM. Exposure of airway epithelium to airborne PM causes altered cytokine/chemokine gene expression and increased production of IL-1\u03b2, IL-6, IL-8 and TNF-\u03b1 . Now, the lung endothelium is also gaining attention as a viable PM target tissue. Exposure of the endothelium to PM or its active components in the systemic circulation induces significant systemic endothelial inflammation and dysfunction, even at low levels of exposure . The water soluble fraction of PM can easily diffuse through the epithelium/endothelial barrier to the systemic circulation. Bioavailable transition metals present in urban PM Title: Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis", "Passage: Despite the fact that the pathogenesis of NEC is considered multifactorial, recently the role of epithelium has emerged as central in the development of NEC. The loss of epithelial barrier allows pathogens translocation from the intestinal lumen to the mucosa . Innate immunity regulates epithelial barrier in experimental model and human cases of NEC.", "Title: RNAi Therapeutic Platforms for Lung Diseases\nPassage: actuation and inhalation coordination. For most MDIs, the propellant is one or more gases called chlorofluorocarbons . Although CFCs in drugs are safe for patients to inhale, they are harmful to the environment. Therefore, further development of inhalable siRNAs may not be the best way forward. DPIs are devices that deliver medication to the lungs in the form of dry powder. The use of DPIs has already shown promise for the in vivo delivery of therapeutic macromolecules such as insulin and low-molecular-weight heparin ; thus, it could be a better device for delivering siRNAs to the lungs. The advantages of Title: Delivery Systems for Intradermal Vaccination", "Passage: Epidermal powder immunization and particle-mediated epidermal delivery utilize helium gas to deliver powdered proteins, polysaccharides, inactivated pathogens, or DNA-coated particles into the epidermis at supersonic speeds . Companies involved in developing this technology include Powderject, PowderMed , and Iaculor Injection. It is not known if this device technology class is still in active development . Conventional protein antigens must be specially formulated for delivery by EPI, and are spray dried into powders of suitable density and size . A clinical trial has been conducted evaluating delivery of a powdered inactivated influenza vaccine by EPI injection, which found that immunogenicity was Title: Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection", "Passage: Some lipid-based preparations have the advantage of being lyophilized, thus allowing to simplify the logistics usually necessary for cold chain. Indeed, some of these formulations can be stored at room temperature for several months and can be administered in such form via the nasal, oral, or sublingual routes. Dry powder nasal vaccines have already been tested , oral delivery of capsules is not a problem , and many allergy-related immunotherapy tablets have been considered for sublingual administration . Moreover, lipid-based preparations can be aerosolized, which might represent an alternative procedure to keeping stable vaccine preparations. Overall, great expectations are coming Title: RNAi Therapeutic Platforms for Lung Diseases", "Passage: The use of aerosols to deliver medication to the lungs has a long history. Administration by inhalation is a popular and non-invasive method of delivering agents into the lungs. There are several inhalation devices available for the delivery of drugs into the lungs. Metered dose inhalers and dry powder inhalers are the most common modes of inhaled delivery. MDIs are the most commonly used inhalers for several lung diseases, such as asthma, bronchitis, and chronic obstructive pulmonary disease , and a spacer is an external device that is attached to an MDI to allow for better drug delivery by enhanced", "Title: We should not be complacent about our population-based public health response to the first influenza pandemic of the 21(st )century\nPassage: The World Health Organization declared that spread of the newly recognised quadruple reassortant influenza A H1N1 virus satisfied the criteria for a pandemic on June 11, 2009 , although technically conditions for declaring a pandemic had been met some weeks earlier. The virus, generally referred to as pandemic influenza H1N1 2009 , had first been recognised in Mexico and the United States in late April 2009. More than a year later, WHO has declared the pandemic to be over and early assessments of the global response have commenced . Title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009", "Passage: Text: In April 2009, the first cases of acute respiratory infections caused by a novel triple-reassortant influenza virus, pH1N1/ 2009v, occurred in Mexico and the United States . The rapid spread of infection to other continents led the World Health Organization to declare on 11 June 2009 that a pandemic of pH1N1/2009v influenza was under way, which raised major international concern about the risk of high morbidity and lethality and the potential for severe socio-economic impact. Actually, the potential impact of this first third-millenium influenza pandemic has been revisited downwards as morbidity and case-fatality rates were less severe than initially Title: Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and fall/winter waves", "Passage: The data was accessed from the Central Epidemic Command Center website of the Taiwan Centers for Disease Control . Samples were collected from hospitals and clinics participating in the Taiwan Influenza surveillance system under the Taiwan National Influenza Center , which was established in 2006 to integrate all existing efforts of influenza surveillance and notification with laboratory analysis systems throughout Taiwan in order to enhance the epidemic data collection capacity in Taiwan . The weekly laboratory confirmed pH1N1 case data and the weekly hospitalization data from June 28, 2009 to March 27, 2010 was accessed from the weekly Influenza Express Title: The epidemiological and public health research response to 2009 pandemic influenza A(H1N1): experiences from Hong Kong", "Passage: identified. Incidence peaked in September, and the first wave petered out by early November. Confirmed pH1N1 infection was a notifiable disease throughout the first wave. Figure 1 summarizes a timeline of the first wave of pH1N1 in Hong Kong.", "Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy\nPassage: Enfuvirtide, also known as T20, was approved by the U.S. FDA as the first HIV entry inhibitor-based antiviral drug for use with other anti-HIV medicines to treat HIV-1 infected adults and children at ages 6-16 years 23,31,32 . Although T20 is an indispensable anti-HIV drug for HIV/ AIDS patients who have failed to respond to the current antiretroviral therapeutics, its shortcomings have limited its clinical application. T20 has lower anti-HIV activity and shorter half-life than other CHR peptides containing PBD, such as C34 and C38 8, 9, 33 . In addition, T20-resistant HIV-1 variants emerged shortly after its use in Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: Enfuvirtide, also known as T20, was approved by the U.S. FDA as the first HIV entry inhibitor-based antiviral drug for use with other anti-HIV medicines to treat HIV-1 infected adults and children at ages 6-16 years 23,31,32 . Although T20 is an indispensable anti-HIV drug for HIV/ AIDS patients who have failed to respond to the current antiretroviral therapeutics, its shortcomings have limited its clinical application. T20 has lower anti-HIV activity and shorter half-life than other CHR peptides containing PBD, such as C34 and C38 8, 9, 33 . In addition, T20-resistant HIV-1 variants emerged shortly after its use in Title: Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41", "Passage: Sifuvirtide is a novel peptide inhibitor developed by Fusogen, Inc. . Its sequence is derived from C34 with some mutations, and the spiral property is enhanced. Similar to C34, sifuvirtide strongly bound to NHR-peptide and significantly inhibited 6HB formation . It also has a more potent anti-HIV activity in vitro than T20 , especially to T20-resistant HIV-1 strains. Sifuvirtide has successfully passed Phase I and II clinical trials in China. Also, the efficacy of sifuvirtide in monotherapy at 20 mg once daily is equivalent to that of enfuvirtide at 90 mg twice daily . However, its further development has been Title: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy", "Passage: Abstract: Enfuvirtide , is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20\u2019s antiviral activity, these antibodies neither", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: It is currently unclear how 2019-nCoV is spread, but it is suspected to be transmitted through contact with infected respiratory secretions, like other known coronaviruses. There are instances of sustained human-to-human transmission across generations of cases, especially near the epicenter in Wuhan City. 21 Current evidence suggests that close contact with an infected person is a major factor in disease transmission. CDC defines \"close contact\" 33 as being in or within two meters of an area with a confirmed patient or being directly exposed to infectious secretions without appropriate PPE. Healthcare facilities in China have reported spread from person to Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Unfortunately, the new virusappears to be spreading from people much earlier in the course of illness, and even with mild symptoms - which was never documented for SARS. However, it is not clear that it is any different or better at spread between people, and perhaps with the same pattern of most cases not causing further spread. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: could be affected by 2019-nCoV. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: 9.", "Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters\nPassage: Alveolar macrophages contribute to the defense against many aerosolized pathogens, and in many cases, these responses are critical for host protection. In models of vaccinia virus, respiratory syncytial virus , and influenza virus infection, the depletion of alveolar macrophages results in greater viral replication and dissemination and an overall increase in the severity of infection . In some cases, the reduced levels of protection in the absence of alveolar macrophages are likely due to the impaired initiation of antiviral responses that result in abolished early cytokine and chemokine release and inhibited immune cell activation and recruitment . In addition, Schneider Title: Innate Immune Response of Human Alveolar Macrophages during Influenza A Infection", "Passage: of the IL-1 receptor by its naturally occurring receptor antagonist IL-1Ra had a similar effect. When the activity of both cytokines was inhibited, there was no further reduction in chemokines greater than that of a single inhibitor, although there was a slight decrease in CXCL10 response in the presence of both inhibitors, the response was not statistically significant. Title: Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages\nPassage: Alveolar macrophage cell line. Murine alveolar macrophage cell line was purchased from American Type Culture Collection . Cells were grown in complete RPMI-1640 medium supplemented with 10% fetal bovine serum and 50 \u03bcM \u03b2-mercaptoethanol and 100 U/ml penicillin and streptomycin at 37\u00b0C and 5% CO 2 . MH-S cells were plated on 6-, 12-or 24-well plates with a density of 3 \u00d710 5 -6 \u00d7 10 5 cells/cm 2 the day before treatment. Title: Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages", "Passage: to effectively enhance M2 polarization of alveolar macrophages in mice while completely abrogating M1 polarization. 61 However, protection was limited to aseptic ARDS conditions, as the complete blocking of classical macrophage activation impaired innate immune response of alveolar macrophages to live bacteria, which is required for effective bacterial clearance. Therapeutic strategies that augment M2 activation but retain M1 plasticity may thus be more favorable for the treatment of acute lung injury. Immunoproteasome-specific inhibition may represent according to our results a more favorable approach for the treatment of pneumonia-or sepsis-related ARDS.", "Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers\nPassage: more conscientious with respiratory etiquette and hand hygiene; attempts to measure these factors were not included in this study. Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: Early in the outbreak it was reported that health workers had not been infected. This was reassuring because it is health workers who many times, and inadvertently, amplify transmission. Failure to wash hands between patients, for example, can result not only in autoinfection, but also in infection of patients hospitalised for other causes when they provide care. Autoinfection is not only a risk for the health worker, but also for their families and the communities in which they live, depending on the transmissibility and means of transmission. More recently infection, and at least one death, in health workers has been Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers", "Passage: Wearing gloves while caring for patients as part of droplet precautions was strongly associated with a lower risk of having had pandemic 2009 virus infection. Use of gloves was highly correlated with use of gowns, masks, and eye protection on logistic regression . This fi nding confi rms the great importance of PPE in preventing transmission of respiratory viruses in the health care setting and may explain why HCWs with defi nite exposure to infl uenza in the workplace, in addition to probable exposure in the community, do not have higher rates of infection than those with only community exposure. Title: Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers\nPassage: infl uenza risk. The reason for the lower risk associated with hospital 2 has not been identifi ed but may relate to other unmeasured factors, such as compliance with hand hygiene procedures.", "Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC\nPassage: Inoculation of RV happens either directly on the nasal mucosa or via the eye conjunctiva where it is transported via the lacrymal duct to the nasal cavity, and then on to the nasopharynx. The airway epithelium is the primary site of infection of RV and it was shown in studies of both natural and experimentally-induced cold that viral RNA cannot be detected in the subepithelial layer, only in epithelial cells. Most RV-A and -B utilize intercellular adhesion molecule -1 as cell entry receptor and the others alternatively bind low density lipoprotein receptor , whereas RV-C utilizes a different receptor molecule Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: Inoculation of RV happens either directly on the nasal mucosa or via the eye conjunctiva where it is transported via the lacrymal duct to the nasal cavity, and then on to the nasopharynx. The airway epithelium is the primary site of infection of RV and it was shown in studies of both natural and experimentally-induced cold that viral RNA cannot be detected in the subepithelial layer, only in epithelial cells. Most RV-A and -B utilize intercellular adhesion molecule -1 as cell entry receptor and the others alternatively bind low density lipoprotein receptor , whereas RV-C utilizes a different receptor molecule Title: Clinical review: Primary influenza viral pneumonia", "Passage: After inhalation, the virus is deposited onto the respiratory tract epithelium, where it attaches to ciliated columnar epithelial cells via its surface hemagglutinin. Local host defenses, such as mucociliary clearance, or secretion of specific secretory IgA antibodies can remove some of the virus particles. However, if mucociliary clearance is impaired or older patients ) or secretory antiinfluenza IgA antibodies are absent , infection continues unabated . Respiratory epithelial cells are invaded, and viral replication occurs. Newer viruses then infect larger numbers of epithelial cells, shut off the synthesis of critical proteins, and ultimately lead to host cell death . Title: Viral factors in influenza pandemic risk assessment", "Passage: Chandrasekaran et al., 2008) . The human upper respiratory epithelium is the primary target site for infection of human-adapted viruses, and infection at this site is thought to be a prerequisite for efficient human-to-human transmission via respiratory droplets. Thus, it appears that human adaptation of an HA is associated with a switch in its binding preference from avian to human receptors. Receptor binding is not either-or; human-adapted influenza virus HA may show some binding to avian receptors, and vice versa.", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: We then did another investigation to find out the dynamic changes of viral presence in two consecutive studies in both oral and anal swabs in another group of patients. The target patients were those who received around 10 days of medical treatments upon admission. We tested for both viral antibody and viral nucleotide levels by previously established method . We showed that both IgM and IgG titres were relatively low or undetectable in day 0 . On day 5, an increase of viral antibodies can be seen in nearly all patients, which was normally considered as a transition from earlier Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Individual human case studies report long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms. In one instance, a HCW shed viral RNA for 42 days in the absence of disease . It is an area of high priority to better understand whether such cases are able to infect others. Over three quarters of MERS cases shed viral RNA in their LRT specimens for at least 30 days, while only 30 % of contacts were still shedding RNA in their URT specimens . Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: patient might still be viremic. Title: Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens", "Passage: Shedding rate Shedding concentrations varied considerably between pathogens as well as between individuals for a given pathogen. We modeled the overall shedding rate as the product of the concentration of pathogen shed per event, the volume of fluid excreted per event, and the number of shedding events. An example of this calculation can be found in the Additional file 1: Appendix. The average shedding rate for influenza was found to be an order of magnitude higher than for rhinovirus and norovirus. Existing studies characterizing the volume and frequency of shedding events were available for influenza and norovirus, but not rhinovirus.", "Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: Any declarative claim that is inconsistent with the information above \"The outbreak began March 2014\" stated after outbreak shown to have begun in December 2013 Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: withdrawn this report. Title: Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak\nPassage: any other statement could suggest doubt . The final error category was statements made without citation to a verifiable source. Title: Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey", "Passage: We have shown that reporting of TBI and its context has changed substantially over time. That our findings were consistent within and across countries, with scientific reporting around TBI and over time provides evidence for the robustness of our findings. Future work that builds upon our findings should focus on how reporting of TBI in ice hockey can affect public discourse and the shaping of programs and policies that have positive effects on public health.", "Title: Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus\nPassage: Here, two VRPs were constructed that contained the GP of EBOV or SUDV. The animals intramuscularly injected with both of the VRPs, survived viral challenge without exhibiting any clinical signs. The final results indicated that VRP-EBOV GP was able to confer cross-protection against SUDV, whereas VRP-SUDV GP was unable to provide complete protection against EBOV-Zaire challenge . Title: Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus", "Passage: The VRPs are the alternative to live-attenuated vaccines. The use of VRPs eliminates the risk of reversion to the original pathogenic form of live vaccine strains. To generate VRPs, generally filoviruses or alphaviruses are required. Here, while keeping the genes essential for replication, viral structural genes are deleted from full-length genomic cDNA clones. Viral structural genes are replaced with alternative gene coding for an immunogen. Such replicons are able to replicate and transcribe upon transfection in competent cells. The resulting VRPs are able to infect cells only for one cycle. Because of the lack of structural genes, viral progeny are Title: Virus-Vectored Influenza Virus Vaccines", "Passage: The VEE replicon systems are particularly appealing as the VEE targets antigen-presenting cells in the lymphatic tissues, priming rapid and robust immune responses . VEE replicon systems can induce robust mucosal immune responses through intranasal or subcutaneous immunization , and subcutaneous immunization with virus-like replicon particles expressing HA-induced antigen-specific systemic IgG and fecal IgA antibodies . VRPs derived from VEE virus have been developed as candidate vaccines for cytomegalovirus . A phase I clinical trial with the CMV VRP showed the vaccine was immunogenic, inducing CMV-neutralizing antibody responses and potent T cell responses. Moreover, the vaccine was well tolerated and Title: Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus", "Passage: not formed. Viruses such as Venezuelan equine encephalitis virus can be used for production of EBOV antigen instead of structural proteins for the replicon vector. Thus, such vaccines are also quite safe . The gene inserted is typically GP, the main target of neutralizing antibodies. VRPs expressing EBOV VP24, VP30, VP35, and VP40 have been evaluated for their protective efficacy in a mouse model, but these were found not to be as protective as EBOV GP and NP antigens. VEEV replicons containing GPs from both EBOV and SUDV showed promising results in cynomolgus macaques after administration of a single dose.", "Title: Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti\nPassage: over five weeks for Survey 1; 257 plates over nine weeks for Survey 2; and 59 plates over four weeks for Survey 3. Together these represent 32,758 participant samples processed over an eighteen-week period. After removal of median fluorescence intensity data across all analytes for samples with missing or high responses to the generic glutathione-S-transferase , 5,898 samples passed QC in Survey 1 ; 21,234 samples in Survey 2 ; and 4,967 samples in Survey 3 . Removal of single analytes' datapoints due to low bead counts accounted for additional minor loss of data . Following these QC checks, there Title: Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti", "Passage: Assay standards. A Haitian positive serum control pool was created using country-wide DBS samples from RDT positive individuals collected during healthcare visits. Blood spots from 63 participants with high responses to a range of Pf antigens were combined and eluted in Buffer B containing 0.5% BSA, 0.05% Tween 20, 0.02% sodium azide, 0.5% polyvinyl alcohol, 0.1% casein, 0.8% polyvinylpyrrolidone and 0.5% w/v E. coli extract) to a whole blood dilution of 1:50 which corresponds to serum dilution of approximately 1:100. The approximate serum concentration is used to indicate the dilution factor throughout the remainder of this report. A 6-point titration Title: Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti", "Passage: curve of the Haitian hyperimmune sera was created in bulk, stored at 4 \u00b0C and used on each assay plate. The first point of this HP curve was a dilution of 1:100 and titrated by 5-fold, meaning the second point was 1:500 up to the sixth point at 312,500. The WHO Pf 10/198 NIBSC standard 22 was eluted in 1.0 ml of dH20 and diluted further in Buffer B. As with the HP curve, a 6-point curve of 5-fold dilutions was prepared in bulk for use throughout the whole study and stored at 4 \u00b0C. As samples and controls were Title: Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti", "Passage: was created using country-wide DBS samples from individuals with confirmed malaria previously collected during healthcare visits. A 6-point, 5-fold titration curve of the HP standard starting at 1:200 was included on every plate, while one using the WHO Pf 10/198 NIBSC standard 22 was included on one plate per day . The highest concentrations of both the HP and the NIBSC positive control standard curves showed robust IgG responses for nearly all of the included Pf antigens . Generally higher MFI responses were seen in the NIBSC standard, likely due in part to the higher serum concentration. The lowest MFI", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: AAV vector systems have a number of engaging properties. The wild type viruses are non-pathogenic and replication incompetent in humans and the recombinant AAV vector systems are even further attenuated . As members of the parvovirus family, AAVs are small non-enveloped viruses that are stable and amenable to long-term storage without a cold chain. While there is limited preexisting immunity, availability of non-human strains as vaccine candidates eliminates these concerns. Modifications to the vector have increased immunogenicity, as well . Title: Viral vector-based influenza vaccines", "Passage: Adeno-associated virus is a parvovirus that is replication-deficient in humans. Like adenovirus, AAV has a broad cell, tissue and host tropism and therefore is a potential good vector vaccine. 218 However, drawbacks of using AAV include: limited capacity for transgenes, presence of pre-existing immunity in humans and the technical challenge of producing high titer stocks. Initially, AAV was not explored as a vaccine vector as it was considered to be poorly immunogenic, however vaccination studies in mice showed that AAV-2 expressing an HSV-2 glycoprotein was immunogenic and a potent inducer of Tcell and antibody responses, 219 and currently modifications are Title: Viral vector-based influenza vaccines", "Passage: being made to AAV to increase immunogenicity. 220 A limited number of studies evaluating AAV as a vector for influenza vaccination has been performed . Initially, an AAV expressing the HA gene or NP gene was shown to be protective in mice. 221, 222 A more recent study tested AAV vaccines expressing the HA, NP or M1 genes of H1N1pdm09 in mice. Whereas AAV-HA afforded full protection from H1N1pdm09 infection, AAV-NP protected mice partially and AAV-M1 did not afford protection. Simultaneous vaccination with all 3 constructs afforded protection from homologous challenge infection. 223 Recently, in an alternative vaccination approach, AAV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adeno-associated viruses were first explored as gene therapy vectors. Like rAd vectors, rAAV have broad tropism infecting a variety of hosts, tissues, and proliferating and non-proliferating cell types . AAVs had been generally not considered as vaccine vectors because they were widely considered to be poorly immunogenic. A seminal study using AAV-2 to express a HSV-2 glycoprotein showed this virus vaccine vector effectively induced potent CD8 + T cell and serum antibody responses, thereby opening the door to other rAAV vaccine-associated studies .", "Title: Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets\nPassage: Abstract: Porcine epidemic diarrhea is a highly contagious disease in newborn piglets and causes substantial economic losses in the world. PED virus spreads by fecal\u2013oral contact and can be prevented by oral immunization. Therefore, it is necessary to develop an effective oral vaccine against PEDV infection. Currently, Bacillus subtilis as recombinant vaccine carrier has been used for antigen delivery and proved well in immune effect and safety. The present study evaluated the immunogenicity of recombinant Bacillus subtilis in piglets via oral administration. After oral immunization in piglets, B. subtilis-RC significantly increased the local mucosal immune responses. Oral administration with B. Title: Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets", "Passage: As a superior way of mucosal immunization, oral administration can protect the gut and stimulate the common mucosal immune system . Besides, oral immunization has several attractive features which include safety, and a straightforward, inexpensive, and needle-free approach . Therefore, oral immunization often delivers large amounts of antigens to prevent the diarrheal diseases . Nevertheless, there are several challenges by oral immunization, which consist of physical, chemical, and biological barriers when delivering antigens to the gastrointestinal tract . Title: Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets", "Passage: It is a substantial problem that digestive acids and proteases can degrade antigen proteins for nutrient absorption . Therefore, the vaccine delivery system has been applied to solve the problem. The system can protect antigens from the severe environment of the GI tract and deliver antigens to intestinal mucosa . Currently, Bacillus subtilis is widely used as a vaccine delivery system for its unique characteristics. Title: Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets", "Passage: As a nonpathogenic Gram-positive bacterium, B. subtilis has been regarded as a novel probiotic and food additive in humans and animals . The B. subtilis has adjuvant activity and can deliver heterologous antigens to the GI tract, providing additional immunity stimulation . Besides, research had shown that orally administered B. subtilis could also enhance immune regulation and gut health in pigs . Moreover, oral administration of B. subtilis could elicit humoral and cellular immune responses to the maintenance of gut homeostasis by dendritic cells . DCs are the most important professional antigen-presenting cells and can effectively regulate antibody titers .", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: With the emergence of 2019-nCoV, real time RT-PCR remains the primary means for diagnosing the new virus strain among the many diagnostic platforms available ; Table S3 ). Among the 16 diagnostics studies selected, one study discussed the use of RT-PCR in diagnosing patients with 2019-nCoV . The period and type of specimen collected for RT-PCR play an important role in the diagnosis of 2019-nCoV. It was found that the respiratory specimens were positive for the virus while serum was negative in the early period. It has also suggested that in the early days of illness, patients have high levels Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: A number of different laboratory diagnostic tests can be used for detecting the presence of novel H1N1 infl uenza virus in respiratory specimens, including direct antigen detection tests, virus isolation in cell culture, or detection of infl uenza-specifi c RNA by real-time reverse transcriptasepolymerase chain reaction . Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus\nPassage: of infl uenza virus genome have advantages over other methods and provide sensitive, highly specifi c and rapid diagnosis. The realtime RT-PCR should be the method of choice and both in-house developed and CDC-developed real-time PCR assays can be used for the specifi c detection of novel H1N1 2009 infl uenza virus. Title: Clinical review: Primary influenza viral pneumonia", "Passage: The real-time reverse transcriptase-polymerase chain reaction Swine Flu Panel for detection of pandemic H1N1 influenza, developed by the Centers for Disease Control and Prevention and distributed to many laboratories in US and worldwide, is a reliable and timely method of diagnosing the pandemic strain . The viral culture, while the gold standard in influenza diagnostics, takes several days before the results are known . The direct fluorescent antigen influenza test was recently reported to have a sensitivity of 93% compared with the rRT-PCR , but the test requires considerable technical expertise in addition to a fluorescent microscope. The commonly used", "Title: Viral vector-based influenza vaccines\nPassage: viral vectors can easily be propagated to high virus titers and it is relatively easy to insert genes encoding antigens of choice into the vector. Viral vector technology also allows the production of modified influenza viral antigens in vivo. These modifications can improve the immunogenicity of the influenza viral proteins or alter the specificity of the immune response. In this review, we discuss reports on vectored influenza vaccines and discuss their advantages and disadvantages. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. Title: Viral vector-based influenza vaccines", "Passage: vivo. Since the proteins are expressed in their native confirmation, antibody responses of the desired specificities are induced. In addition, viral vectors allow de novo protein synthesis in the cytoplasm of infected cells facilitating endogenous antigen processing and MHC class I presentation of immunogenic peptides, which is a requirement for the efficient induction of virus-specific CD8 C T-cell responses. Although all vectors discussed have their own respective advantages and disadvantages, most are replication-deficient in mammalian host cells and are therefore safe for human use, even in immunocompromised individuals. Pre-existing immunity to the vector may pose a problem for some vectors, Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Influenza vaccines utilizing vesicular stomatitis virus , a rhabdovirus, as a vaccine vector have a number of advantages shared with other RNA virus vaccine vectors. Both live and replication-defective VSV vaccine vectors have been shown to be immunogenic , and like Paramyxoviridae, the Rhabdoviridae genome has a 3'-to-5' gradient of gene expression enabling attention by selective vaccine gene insertion or genome rearrangement . VSV has a number of other advantages including broad tissue tropism, and the potential for intramuscular or intranasal immunization. The latter delivery method enables induction of mucosal immunity and elimination of needles required for vaccination. Also, there", "Title: A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells\nPassage: To further study the effect of cholesterol depletion on the interaction between the TPIC and CAV1, cells were pre-treated with M\u03b2CD and incubated with TPIC as previously mentioned. After being fixed, cells were incubated with a DyLight 488-labelled anti-human CAV1 monoclonal antibody at 4 1C overnight. After extensive washing, the cells were stained by Hoechst33342, and the glass bottom dishes were examined under a confocal scanning microscope. Title: A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells", "Passage: to stain the nucleus as a control. After extensive washing, the glass bottom dishes were examined under a Zeiss LSM700 laser confocal scanning microscope. Title: A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells\nPassage: To further study the interaction between TPIC and CAV1, cells were treated with fresh serum free media containing DOX-loaded TPIC for 4 h at 4 or 37 1C. Then, cells were fixed and incubated with a DyLight 488-labelled anti-human CAV1 monoclonal antibody at 4 1C overnight. After extensive washing, the cells were stained by hoechst33342, and the glass bottom dishes were examined under a confocal scanning microscope. Title: A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells", "Passage: were enhanced compared with antibody. Notably, although the pattern was less conspicuous, cross-linked CD13 molecules after TPIC treatment showed a streaky distribution along longitudinal lines . This phenomenon was probably because the cross-linking of CD13 by TPIC would induce binding to actin filaments, either directly or indirectly, and further cause the longitudinal alignment. This similar distribution was also reported for cross-linked \u03b22-microglobulin 44 and HCoV-229E 45 and both were eventually internalized by the CvME.", "Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: We also compared and contrasted the clinical and community results. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses found in the clinical sample. These three infections resulted in 41 viruses detected in 15 subjects clinically, and eight infections detected in five people in the community. Together they infected 94% of clinical subjects, and 7% in the community . The most common virus detected in community samples was Coronavirus OC43; this virus was detected in 13.3% people in the community and not in any of the clinical samples. However a different strain, coronavirus OC 229 Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% of clinical subjects, and 6.7% of community subjects . Coronavirus OC43 was the most common virus detected in community members . A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Basic participant demographics are summarized in PCR results showed that ten different viruses were detected. Figure 1 shows how these infections were distributed across virus types as well as in the community versus clinic samples. In sum, a total of 33 of the 91 subjects surveyed had one or more respiratory tract virus . Furthermore, 10 of those cases were triple infections and 5 were quadruple infections . Figure 2 indicates how frequently each pair of viruses were found in the same participant; co-infections were most common among enterovirus and parainfluenza virus 4 . Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: We identified ten different respiratory tract viruses among the subjects as shown in Fig. 1 . Samples collected from the Children's specialist hospital showed 100% prevalence rate of infection with one or more viruses. This might not be surprising, as the basic difference between the community and clinic samples was an increased severity of illness in the clinical sample. This may also explain the high level of co-infection found among the clinical subjects. The most prevalent virus in the clinical sample was not detected in the community sample. Further, there was a significant difference between prevalence of the most common", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In the only study to examine the effect of sample type on molecular analysis, 64 nasopharyngeal aspirates , 30 tracheal aspirates, 13 sputa and three BAL were examined. The tracheal aspirates and BAL returned the highest viral load values followed by NPA and sputum. Unsurprisingly, higher viral loads generally paralleled whole genome sequencing and culture success and, in NPA testing, were significantly correlated with severe disease and death . This study demonstrated the importance of LRT sampling for whole genome sequencing. Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: well-tolerated in healthy participants. Where the biological samples are taken from also play a role in the sensitivity of these tests. For SARS-CoV and MERS-CoV, specimens collected from the lower respiratory tract such as sputum and tracheal aspirates have higher and more prolonged levels of viral RNA because of the tropism of the virus. MERS-CoV viral loads are also higher for severe cases and have longer viral shedding compared to mild cases. Although upper respiratory tract specimens such as nasopharyngeal or oropharyngeal swabs can be used, they have potentially lower viral loads and may have higher risk of false-negatives among Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms. LRT samples are also best for attempting isolation of infectious virus, although the success of culture is reduced when disease persists . Recommended sample types include bronchoalveolar lavage , tracheal/tracheobronchial aspirate, pleural fluid and sputum . Fresh samples yield better diagnostic results than refrigerated material and if delays in testing of \u226572 h are likely, samples should be frozen at \u221270\u00b0C . If available, lung biopsy or autopsy tissues can also be tested . Title: Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt", "Passage: In total, 520 patients were prospectively enrolled in this study. To increase the number of virus-positive samples more than one specimen per patient was collected. Specimens were nasal swabs , throat swabs , nasal aspirates , tracheal aspirates , bronchoalveolar lavages , gargles , and sputum . Samples were collected into sterile cups containing phosphate buffered saline as virus transport medium. Aliquots from each sample were done and stored at \u221280 \u2218 C until the samples were finally shipped to the National Influenza Center, Robert Koch Institute, Germany, where the laboratory and the phylogenetic analyses were conducted.", "Title: Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype\nPassage: doi:10.1371/journal.ppat.1004838.g002 tolerated. To confirm these modelled predictions, we generated each mutation on both backgrounds and measured the relative fitness. Indeed, the D138G mutation alone on the WT background conferred nearly a ten-fold drop in fitness and the Q234K mutation conferred up to 100-fold drop in fitness , while the fitness costs of these mutations on the E76G background resulted in neutral fitness relative to WT. The data suggest that epistasis between these mutations and the E76G mutation rescues the fitness of these double variants and permits their positive selection in the viral population. Interestingly, the D138G and Q234K variants seemed Title: Virus Adaptation by Manipulation of Host's Gene Expression", "Passage: To further characterize the relationship between these changes and symptoms severity, we introduced them by site-directed mutagenesis in the ancestral TEV clone. In addition, all three possible pairs of non-synonymous mutations and the triple non- synonymous mutant were also created. A. thaliana Ler plants were inoculated with these nine mutant clones and maintained in the same growth conditions for three weeks. The results of this experiment are summarized in Table 1 . All mutant genotypes were viable and replicated and accumulated in the plants, as confirmed by Western blot analysis . Among the three single mutants, the only clone that Title: Virus Adaptation by Manipulation of Host's Gene Expression", "Passage: The seven mutant genotypes created in this study were generated by site-directed mutagenesis using the QuikchangeH II XL kit and following the indications of the manufacturer. Mutagenic primers were also designed according to Stratagene recommendations. To minimize unwanted errors during the mutagenesis process, the kit incorporates the PfuUltra TM high fidelity DNA polymerase. The presence of the desired mutation was confirmed by sequencing. To assess the presence of undesired mutations on each clone, the Surveyor TM Mutation Detection Kit Standard Gel Electrophoresis was employed. All six mutant genotypes presented the expected genome-wide band pattern. Title: Host shifts result in parallel genetic changes when viruses evolve in closely related species", "Passage: One mutation rose to a high frequency across all the host species . This is unlikely to be an error in the genome sequencing, as it did not occur when we sequenced the ancestral virus. This may have been due to natural selection favouring this change in all species, perhaps because there was a strongly deleterious mutation at this site in the virus we cloned or due to the virus going from cell culture to being passaged in vivo.", "Title: A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer\nPassage: spectrofluorometry at l ex 485/20 nm and l em 645/40 nm . Title: N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice\nPassage: fluorescence window value at each time point. Lifetime slopes were calculated using each Lifetime measurement over time. Data are presented as mean \u00b1 standard error . The differences between the control and compound treated wells were analyzed using the Student's t-test. A value of p\ufffd0.05 was considered statistically significant. Title: A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer", "Passage: To determine the presence of the drug localized in tumor tissues, doxorubicin autofluorescence was detected using a Zeiss Axiovert 200 M inverted microscope with a 100 W HBO mercury light source equipped with a 546/12 nm excitation and a 590 nm emission filter set. Tissue sections were imaged with a FLUAR 106/0.50 NA lens and captured with a Roper Scientific CoolSnap HQ CCD camera. All images were captured in 8-bit signal depth and subsequently pseudo-colored. Title: N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice", "Passage: the well. The score is normalized per-plate to 0-100% effect using the \"unstimulated control\" and \"stimulated + DMSO Vehicle\" as controls. This bio-imaging platform consistently yielded an average Z-prime factor above 0.49. Moreover, the assay includes an internal measure to evaluate in vitro liver toxicity based on the nuclei counting feature using the Hoechst channel. Compounds were considered toxic if the cell count fell below 80% of the vehicle control values for cell number.", "Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria\nPassage: We identified ten different respiratory tract viruses among the subjects as shown in Fig. 1 . Samples collected from the Children's specialist hospital showed 100% prevalence rate of infection with one or more viruses. This might not be surprising, as the basic difference between the community and clinic samples was an increased severity of illness in the clinical sample. This may also explain the high level of co-infection found among the clinical subjects. The most prevalent virus in the clinical sample was not detected in the community sample. Further, there was a significant difference between prevalence of the most common Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: The main limitation of the study is the sample size. In particular, the sample is not equally representative across all ages. However, the sample size was big enough to ascertain significant differences in community and clinic sourced viruses, and provides a qualitative understanding of viral etiology in samples from the community and clinic. Moreover, the sample was largely concentrated on subjects under 6 years, who are amongst the groups at highest risk of ARIs. Despite the small sample size, samples here indicate that circulation patterns in the community may differ from those in the clinic. In addition, this study resulted Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Disease Surveillance and Notification Officers, who are employed by the State Ministry of Health and familiar with the communities in this study, performed specimen and data collection. Symptoms considered were derived in accordance with other ARI surveillance efforts: sore throat, fever, couch, running nose, vomiting, body ache, leg pain, nausea, chills, shortness of breath . Gender and age, type of residential area , education level, proximity of residence to livestock, proximity to an untarred road and number of people who sleep in same room, were all recorded. The general difference between the two settings was that those from the hospital Title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria", "Passage: Basic participant demographics are summarized in PCR results showed that ten different viruses were detected. Figure 1 shows how these infections were distributed across virus types as well as in the community versus clinic samples. In sum, a total of 33 of the 91 subjects surveyed had one or more respiratory tract virus . Furthermore, 10 of those cases were triple infections and 5 were quadruple infections . Figure 2 indicates how frequently each pair of viruses were found in the same participant; co-infections were most common among enterovirus and parainfluenza virus 4 .", "Title: Estimating the number of infections and the impact of non-\nPassage: interventions became effective. Title: Estimating the number of infections and the impact of non-\nPassage: Following the hierarchy from bottom to top gives us a full framework to see how interventions affect Title: Estimating the number of infections and the impact of non-\nPassage: interventions. Title: Estimating the number of infections and the impact of non-\nPassage: Figure 15: Effects of different interventions when used as the only covariate in the model.", "Title: Advanced Molecular Surveillance of Hepatitis C Virus\nPassage: HCV is spontaneously cleared by the host in up to 15% of acutely infected individuals . It has been reported that an early functional inactivation of the HCV-specific CD4+ T cell response may play a major role in establishing viral persistence , and such dysfunctional T cells can be functionally reactivated . Several studies have suggested that differences in host immune responses determine viral clearance. Indeed, the intensity of the immune response can be dictated, at least in part, by host genetic factors . However, the role of host factors in HCV clearance is not well understood. Different studies have Title: Type III Interferons in Hepatitis C Virus Infection", "Passage: in patients chronically infected with HCV . However, this was not confirmed in two other independent studies in Japanese or Italian cohorts . Finally, HCV-related liver disease is a multifactorial problem, and the independent association of genetic factors may not be a clear cut. Fortunately, with the development of highly effective DAAs, it is expected that these complications will be less frequent as SVR will be achievable in most patients. Type III IFNs in HCV Infection Frontiers in Immunology | www.frontiersin.org December 2016 | Volume 7 | Article 628 Title: The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy", "Passage: Worldwide 92-149 million people, representing approximately 2% of the world's population, are chronically infected with HCV , one of the causative agents of viral hepatitis. HCV is a blood borne virus and transmission occurs parenterally, mainly by reusing injection material, insufficient sterilization of medical tools, or by transfusion of unscreened blood or blood products. As screening of blood products is a standard procedure nowadays in most countries, people who inject drugs have the highest risk of contracting hepatitis C. In fact, over 60% of injecting drug users are positive for HCVantibodies . Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: public health authorities , they are not currently financially covered, except in specific cases. Despite the high rates of viral response achieved with DAA-based treatments, still 1 to10% of the patients fails to eliminate infection, and in these cases, baseline and emergent resistance variants turn out to be key factors contributing to treatment failure .", "Title: Use of functional gene arrays for elucidating in situ biodegradation\nPassage: to maximize the visible variability of the data or hierarchical cluster analysis , which groups communities based on the similarity of their gene profiles, can be used. To compare communities, response ratios, which compare the signal intensity of genes between conditions , t-tests, ANOVA, and dissimilarity tests can be used. Several methods can be used to examine the relationship between communities and environmental parameters. These include constrained ordination, such as canonical correspondence analysis , distance-based redundancy analysis , variation partitioning analysis , and Mantel test. A relatively new analysis method is the random matrix theorybased neural network analysis used to Title: Use of functional gene arrays for elucidating in situ biodegradation", "Passage: Due to the large volume of data obtained from GeoChip, data analysis can be very challenging. The data has a multivariate structure and the number of variables is much larger than the number of observations . To assist users with data analysis steps, a pipeline is available which performs many of the common analyses 3 . Some common descriptive statistics used include relative abundance of gene categories or subcategories, richness and diversity indices, and percentages of gene overlap between samples. To compare the overall community structure, unconstrained ordination and correspondence analysis ] to reduce the dimensionality of variables in order Title: Gain-of-Function Research: Ethical Analysis", "Passage: While Kirsten Jacobson and colleagues suggest that, in light of measurement difficulties, '' qualitative risk-benefit analysis framework for assessing research\u2026would be the most decisive tool for asking the hardest and most important questions'' , Marc Lipsitch and Thomas Inglesby argue that risk-benefit analysis can and should be quantitative because ''xtensive qualitative arguments have not provided sufficient clarity or evidence to resolve concerns or identify a consensus path forward \u2026 this process should be quantitative, rather than relying on unquantified and unverifiable assurances that particular laboratories are safe'' . Though they admit measurement challenges associated with objective quantitative risk-benefit analysis, Arturo Title: Gain-of-Function Research: Ethical Analysis", "Passage: There may be cases where the very same option promotes all three of these things at the very same time-and in cases like that it might be quite obvious what should be done. In other cases there might be conflict between these three arguably legitimate goals of decision-making. Such cases raise difficult questions about the weightings that should be attributed to such goals and/or how to strike a balance, or make trade-offs, between them. The hypothetical examples discussed above suggest that the weightings attributable to such goals may be context dependent-e.g., maximin might be especially weighty in high risk situations,", "Title: Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein\nPassage: transduction, the MLV particles were 5 to 10 times concentrated using a 100-kDa concentrator . For the generation of single-cell clones stably expressing GFP, BGM and HeLa cells were transduced and grown in the presence of puromycin to generate pools of GFP-expressing cells, which were subsequently used to prepare single-cell clones by limiting dilution. Expression of GFP was monitored during passaging by immunofluorescence microscopy using the GFP antibody. Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: After application of the overlay, plates were monitored periodically using an inverted fluorescence microscope until the first signs of GFP expression were witnessed . From that time forward, a square subset of the center of each well was imaged periodically, using a CellInsight CX5 High Content Screening Platform with a 4X air objective . Microscope settings were held standard across all trials, with exposure time fixed at 0.0006 s for each image. One color channel was imaged, such that images produced show GFP-expressing cells in white and non-GFP-expressing cells in black . Title: Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy", "Passage: express cytoplasmic fluorescent proteins driven e.g., by the chicken \u03b2-actin promoter with cytomegalovirus enhancer or human ubiquitin C promoter . Many different mouse lines are available that contain reporter genes for cytoplasmic fluorescent proteins such as EGFP and mCherry . Due to strong and continuous expression rate of the fluorescent proteins long-term tracking of dividing cells without extensive bleaching is possible. In addition, with a superior signal-to-noise ratio visualization of small cellular structures with low cytoplasm content is feasible. Although the approach to adoptively transfer fluorescent cells of interest into donor mice for functional imaging studies is fast and flexible, Title: Replication-Competent Influenza A Viruses Expressing Reporter Genes", "Passage: lungs. Not only was GFP observable in the lungs of infected mice ex vivo using IVIS for whole-organ imaging, but could also be observed using flow cytometry to analyze the infection progression in antigen presenting cells . Imaging of murine lungs showed that infection starts in the respiratory tract in areas close to large conducting airways and later spreads to deeper sections of the lungs . The authors found that using a 10 6 PFU intranasal inoculation, 10% of dendritic cells were observed to express GFP and 2%-3% of macrophages and neutrophils were also GFP+ at 48 h post-infection .", "Title: Neutralization Interfering Antibodies: A \u201cNovel\u201d Example of Humoral Immune Dysfunction Facilitating Viral Escape?\nPassage: Text: Hypervariable viruses adopt several mechanisms to cope with the host humoral immune response. The most studied mechanism is the accumulation of point mutations on immunodominant regions of surface proteins, making them no longer recognizable by previously generated neutralizing antibodies . Other escape mechanisms involving surface proteins include glycosylation of functionally pivotal residues or their association with host serum components in order to mask them from the immune system . Other known escape mechanisms are a sort of protected route of virus spreading, such as cell-to-cell transmission ; the molecular mimicry between viral proteins and host self-antigens or the viral-induced Title: Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines", "Passage: With the viral proteins being folded differently, the degree of exposure of these neutralizing epitopes is different among the subgenogroups. This, hence, would lead to the differences in the amount of universal neutralizing antibodies produced, translating to the different neutralizing capacity observed. Title: Neutralization Interfering Antibodies: A \u201cNovel\u201d Example of Humoral Immune Dysfunction Facilitating Viral Escape?", "Passage: The basic genome organization and replicative cycle is similar for all CoVs. Gene 1 encodes all predicted replicase/transcriptase proteins, which are translated from input genomic RNA, while genes 2-9 encode structural and accessory proteins, including the envelope spike protein, which are translated from separate subgenomic mRNAs. CoVs use a unique discontinuous mechanism to transcribe a series of progressively larger subgenomic mRNAs, and each contains a leader RNA sequence that is derived from the 5' end of the genome . Title: Emergence of a Large-Plaque Variant in Mice Infected with Coxsackievirus B3", "Passage: Many viruses attach to cells by binding HS or other GAGs . For some viruses, GAGs are bona fide receptors. Other viruses have nonglycan proteinaceous receptors, but binding to GAGs can enhance attachment. GAGs most commonly interact with viral particles via positively charged amino acids such as lysine or arginine . Therefore, the N63Y amino acid change observed here is slightly unusual. It is possible that a change from asparagine to tyrosine disrupts GAG binding to a nearby site on the viral capsid or that noncanonical GAG-capsid interactions occur.", "Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters\nPassage: Serial sections of lung tissue from these groups further revealed the presence of ANDV antigen colocalized to CD31-positive endothelial cells in both capillaries and larger vessels . Regardless of treatment, no differences were observed in the pathogenesis of HPS-like disease in ANDV-infected hamsters. Hamsters in all groups exhibited signs of mild to moderate inflam- mation, interstitial pneumonia, alveolar fibrin deposition, and edema characteristic of ANDV infection. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: abundantly in the microvascular endothelium. ANDV-infected hamsters fitted with physiologic monitoring devices exhibited diminished pulse pressures, tachycardia, and hypotension that appear to closely mimic the shock that is believed to be the proximate cause of demise in patients who succumb to HCPS . Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Compared to the human disease, ANDV-infected hamsters exhibit exceptionally high titers of live ANDV in their tissues, with much of the viral replication occurring in hepatocytes, which are spared in the human disease. Titers of live ANDV in some cases exceed 10 8 /g, whereas hantavirus isolates from human tissues have been notoriously difficult to obtain. Despite the universal occurrence of mildly-elevated hepatic enzymes in patients with HCPS, hepatic enzymes do not appear to be present at elevated levels in the blood of diseased hamsters even immediately before death . Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters", "Passage: progresses. At later times after infection, similar levels of viral genome and/or infectious virus were found in the lung of all hamsters, supporting the argument that AM contribute more substantially to the immune response against ANDV early after infection but less so at later times once ANDV is primarily replicating in endothelial cells. This is also consistent with the reduced numbers of AM detected on day 17 compared to day 10.", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: The extent of aquaculture is a known risk factor , possibly because water bodies offer routes for transmission and persistence of the virus. The percentage of land under aquaculture was used as a metric. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: The extent of aquaculture is a known risk factor , possibly because water bodies offer routes for transmission and persistence of the virus. The percentage of land under aquaculture was used as a metric. Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: has been proven that farm duck breeds can shed the H5N1 virus with minimal clinical signs , our results suggest that farm ducks may also have played the role of silent carriers during the second wave of the epidemic, contributing to the spread of the disease. In addition, an increased risk in duck flocks was shown for subdistricts with a high density of broiler and layer chickens . In Thailand, broiler and layer chicken production range from large-scale industrial farms to small, family-run operations . The latter refer to small or medium-scale businesses with links to several middlemen or companies Title: Anthropogenic factors and the risk of highly pathogenic avian influenza H5N1: prospects from a spatial-based model", "Passage: in Southeast Asia has been linked to a specific agro-ecosystem that associates freegrazing ducks with rice cultivation. A separate study found that the risk of HPAI outbreaks was reduced in areas with agricultural activities other than rice farming . Free-grazing ducks form a reservoir of HPAI H5N1 in Asia and may contribute to the spread of the virus when they are moved among rice fields which also constitute a habitat for wild waterfowl . In addition to free-grazing ducks, it is likely that backyard poultry raised in low biosecurity systems and fighting cocks are involved in the diffusion of the", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: gained favour, as E. coli is a commensal and lactic acid bacteria are present in most fermented food items and are therefore naturally present in the host. They are also a much safer option than traditional attenuated vaccines in children and immunecompromised people. As this review discusses the effects of pre-existing immune responses to attenuated vaccines, further discussion of LAB and E. coli as potential vectors will not be undertaken; however, the reader is directed to several interesting reviews . Intracellular bacteria from the genera Mycobacterium , Listeria , Shigella and Salmonella are considered to be suitable candidates for the Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Text: In the fields of medicine and veterinary medicine, there are numerous live, attenuated bacterial and viral vaccines in use today worldwide. The safety and efficacy of such vaccines is well established and allows further development as vector systems to deliver antigen originating from other pathogens. Various attenuated bacteria, including Escherichia coli, Vibrio cholerae, lactic acid bacteria , specifically Lactococcus lactis, Mycobacterium, Listeria, Shigella and Salmonella, have been tested for the targeted delivery of heterologous antigens of bacterial, viral and parasitic origin into a variety of animal hosts . Bacteria such as E. coli and lactic acid bacteria have recently Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: LAB is an excellent candidate to be manipulated as a DNA vaccine carrier. LAB has been used in food fermentation for centuries and is a Generally Recognized as Safe organism . LAB is also resistant to acidic conditions in the gastrointestinal system and is able to deliver the vaccine to the intestinal area . Several LAB strains are famous as probiotic bacteria, such as Lactobacillus casei, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum and Lactobacillus reuteri. Probiotic bacteria reduce lactose intolerance symptoms, such as diarrhea and flatulence, which appear in lactose intolerant patients who consume milk. Probiotic bacteria also Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Lactococcus lactis is the most-studied LAB since its genome is easily manipulated, and many genetic tools have been engineered for L. lactis . Notably, one of the main advantages of using L. lactis as a DNA vaccine carrier is its ability to pass through the intestinal tract without colonization .", "Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo\nPassage: These data show that rVSV can spread in a retrograde direction from the injection site, but do not address whether the virus can spread exclusively in the retrograde direction. Directional transsynaptic specificity can only be definitively addressed using a unidirectional circuit. We therefore turned to the primary motor cortex to CP connection, in which neurons project from the cortex to the CP, but not in the other direction . Injections of rVSV into M1 should not label neurons in the CP if the virus can only label cells across synapses in the retrograde direction. Indeed, at 2 dpi, areas directly Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: These data show that rVSV can spread in a retrograde direction from the injection site, but do not address whether the virus can spread exclusively in the retrograde direction. Directional transsynaptic specificity can only be definitively addressed using a unidirectional circuit. We therefore turned to the primary motor cortex to CP connection, in which neurons project from the cortex to the CP, but not in the other direction . Injections of rVSV into M1 should not label neurons in the CP if the virus can only label cells across synapses in the retrograde direction. Indeed, at 2 dpi, areas directly Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo", "Passage: dpi, as previously observed . Labeling remained well-restricted to the expected corticostriatal circuits at 5 dpi, suggesting that viral spread becomes less efficient after crossing one or two connections, consistent with injections into V1 . While glial cells can be infected and were observed near the injection site , infected glial cells away from the injection site generally were not observed. Title: Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo\nPassage: dpi, as previously observed . Labeling remained well-restricted to the expected corticostriatal circuits at 5 dpi, suggesting that viral spread becomes less efficient after crossing one or two connections, consistent with injections into V1 . While glial cells can be infected and were observed near the injection site , infected glial cells away from the injection site generally were not observed.", "Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology\nPassage: The case example book, which resulted from this study, constitutes a detailed feed back for the participants of the study and is now being used as training material for public health nurses. Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology\nPassage: The case examples consisted in facsimile excerpts of one or more of the following sources: laboratory report form, physician form, and protocol of the patient interview . The case examples were created based on real cases that have come to the attention of the RKI in the quality control process and in the information service hotline that the RKI is offering to the health departments. Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology", "Passage: Three-hundred and three of 347 health departments stated that case classifications were done exclusively or primarily by public health nurses. With respect to the case examples presented to the participants, 220 of 396 respondents stated that the case examples were realistic. Title: Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology", "Passage: To specifically assess the effect of different styles in formulating case definitions, a fourth outcome variable was used. The clinical classification was considered correct if the part regarding the clinical picture was classified according to the gold standard, regardless whether other parts of the case definition were correctly classified or not. This analysis was done to compare case definitions with narrative description of the clinical pic-ture to case definitions with a more explicit check-list format of clinical criteria, that was implemented for diseases additionally notifiable in specific states and for the new IfSG case definitions.", "Title: Detecting a Surprisingly Low Transmission Distance in the Early Phase of the 2009 Influenza Pandemic\nPassage: Our results support the idea already presented by Birrell et al. 53 that the geographic spread of influenza might be inaccurately described by raw commuting fluxes. However, although our results point in the direction of a human behavioral adaptation to the pandemic threat, they are far from conclusive. In fact, other factors could have been responsible for the changes in the force of infection that we measured. Clearly, data quality and availability impose several limitations on our modeling analysis. First, concerning the initial seeding of the infection, we compute the region-specific probability of importing cases by using data on the Title: Estimating the number of infections and the impact of non-\nPassage: gives a systematically biased view of trends. Title: Estimating the number of infections and the impact of non-", "Passage: with a high level of uncertainty. Title: Estimating the number of infections and the impact of non-\nPassage: Social distancing encouraged: As one of the first interventions against the spread of the COVID-19", "Title: Max Bergmann lecture Protein epitope mimetics in the age of structural vaccinology\u2021\nPassage: Much of the work reviewed here has been focused upon the design of b-hairpin mimetics, based on motifs seen in protein crystal structures. b-Hairpin motifs are often found in proteins to mediate protein-protein and protein-nucleic acid interactions. A b-hairpin is comprised of two consecutive hydrogenbonded antiparallel b-strands connected by a loop sequence. Many variations are observed in backbone conformation in b-hairpin loops in folded proteins, depending upon the hydrogen bonding pattern between the two antiparallel b-strands and the loop length ). This structural diversity can be captured, at least to some extent, in b-hairpin mimetics designed by transplanting the hairpin Title: Max Bergmann lecture Protein epitope mimetics in the age of structural vaccinology\u2021", "Passage: Most b-hairpins in proteins of known 3D structure have loops of \u22645 residues . In two residue hairpin loops, type I 0 and II 0 b-turns are strongly favored over type I and type II b-turns. A type I 0 b-turn was observed at the tip of a 12-residue b-hairpin mimetic derived initially from the Tat protein, which binds to a nucleic acid target, the transactivation response element RNA of HIV-1 . The mimetic was found to adopt stable b-hairpin structures in free solution and when bound in the major groove of the TAR RNA hairpin . In the RNA-peptidomimetic Title: Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch\nPassage: hairpins and pseudoknots, function as a structural domain or subdomain . Title: Stem\u2013loop structures can effectively substitute for an RNA pseudoknot in \u22121 ribosomal frameshifting", "Passage: the overall destabilizing effect of mismatches in DNA hairpins. In a pioneer singlemolecule pulling study, it was shown that introducing a mismatch in a 20 bp DNA hairpin shifted its transition state close to the location of the mismatch . Our data also comply with this mechanical study and suggest that mechanical stability may be a better parameter than thermodynamic stability to describe the frameshift efficiency of hairpins.", "Title: The origins of the great pandemic\nPassage: Because the 1889 pandemic unfolded with three major waves worldwide from 1889 to 1892 , with the 1892 wave being the most intense, at least on the East Coast of the USA, it seems worth considering whether so-called herald waves of the 1918 pandemic might have stretched back all the way to 1915. Viruses with identical or nearly identical genome sequences to those in the fall wave were circulating in early 1918 , at a time prior to the recognition of a new pandemic. It is perhaps not so great a leap to imagine that these viruses were related to Title: The epidemiological and public health research response to 2009 pandemic influenza A(H1N1): experiences from Hong Kong", "Passage: of convalescent plasma to treat severe infections was shown to be feasible in a pandemic 57 and evidence of its effectiveness albeit from a small study should justify further studies. 56 While we focused on research into the epidemiology, impact, and control of pH1N1, much important research on pH1N1 has been carried out in other areas outside the scope of our review. To give two specific examples, local researchers confirmed the origins of the 2009 pandemic strain by comparison with a detailed local swine influenza surveillance program, 65 and performed important basic studies on pathogenesis. 66 Two sets of studies Title: Economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories", "Passage: Several related studies which also used individualbased simulation models of influenza spread coupled with costing models are those of those of Sander et al., Perlroth et al., Brown et al., and Andradottir et al. . The current study extends upon the scope of these studies in several ways: five gradations of pandemic severity are considered, more combinations of interventions are considered, social distancing interventions of varying durations are considered, and probabilities of severe health outcomes for each severity category are based on fatality, hospitalization and ICU usage data as observed from the 2009 pandemic. Also in contrast with those models, Title: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic", "Passage: When there is more than one wave of infections, as in our current study, a variation of the Richards model can be utilized, which makes the distinction between two types of turning points ; one type which occurs at the peak incidence, and a second type which occurs in a multi-wave epidemic when the growth rate of the cumulative case number begins to increase again, indicating the beginning of the next wave.", "Title: Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents\nPassage: For the RTI outbreaks, sex and LOS variables did not have a significant effect. In residents older than 86, the odds of being infected in Flu+ context were 1.5 times higher for women and 1.7 for men. In univariate analysis, contrary to the other virus contexts where odds ratios were rarely above 2, residents over 95 years old had increased odds of infection of \ufffd 2.8 compared with the 70-year-old category, and for the 100 year-old group the odds were approximately 3.8. In the Flu+ context, autonomy adjusted for age revealed a possible increase in infection rates among less autonomous Title: Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016", "Passage: There were differences between nosocomial influenza patients and those who were not. Nosocomial influenza cases had a higher frequency of age 65-74 years , and \u2265 75 years , diabetes , chronic renal disease , immunodeficiency , chronic cardiovascular disease and chronic liver disease . Influenza vaccination uptake was higher in nosocomial influenza patients . Title: Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents", "Passage: Older age appeared to increase the likelihood of GE and influenza infection, with increasing rates among older residents. Age is a well-known factor for influenza and norovirus severity in the elderly and in nursing homes . For NoV, the highest incidence estimates was found in the \ufffd85 year-category . In our study, univariate analysis showed that the odds of being infected were 1.5 to 1.6 times higher if a resident was older than 85. Moreover, an adjusted analysis of GE outbreaks highlighted different effects among subgroups of residents according to sex and LOS. Indeed, multiple and/or repeated exposure to GE Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years .", "Title: Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival\nPassage: Smoking was reported in 15.5% patients. Common risk factors for staphylococcal infection, such as diabetes, steroid therapy, and immunosuppressive treatment, were noted for 6.1%, 6.8% and 5.4% of patients, respectively. Among the 126 patients for whom data were available, 10.3% had a personal history of furuncles or skin abscess. Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: Staphylococcus aureus colonizes persistently about 30% of the human population and typical niches include nares, axillae, and skin . They cause a variety of clinical manifestations ranging from mild skin infections to fatal necrotizing pneumonia. In the last decades, the pathogen became resistant to an increasing number of antibiotics and methicillin-resistant S. aureus is now a major cause of hospital acquired infections . Also the rise of community-acquired S. aureus strains is of special concern, because certain clones are associated with very severe infections . Recent prospective studies demonstrated an increase in proportion of communityacquired methicillin-sensitive S. aureus in severe Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: Staphylococcus aureus colonizes persistently about 30% of the human population and typical niches include nares, axillae, and skin . They cause a variety of clinical manifestations ranging from mild skin infections to fatal necrotizing pneumonia. In the last decades, the pathogen became resistant to an increasing number of antibiotics and methicillin-resistant S. aureus is now a major cause of hospital acquired infections . Also the rise of community-acquired S. aureus strains is of special concern, because certain clones are associated with very severe infections . Recent prospective studies demonstrated an increase in proportion of communityacquired methicillin-sensitive S. aureus in severe Title: Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival", "Passage: Since 1986, the French National Reference Centre of Staphylococci has collected 161 case reports of documented pneumonia caused by S. aureus strains carrying PVL genes . Informed consent was waived because data were extracted from the surveillance database. According to French law, a study like this one does not require ethics committee approval because it is observational and based on a surveillance database approved under national regulations. The protocol design was approved by the hospital's institutional review board .", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: can explain pain associated with CHIKF . Title: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity\nPassage: CHIKV infection is clinically characterized by the sudden appearance of high fever, rash, headache, nausea, vomiting, myalgia and arthalgia or severe joint pain. Severe joint pain is the defining symptom of CHIKV disease . The word Chikungunya originated from the Tanzanian and Mozambique region of Africa meaning that which bends up. A bent posture is often taken by those in severe joint pain after being infected with CHIKV. CHIKV symptoms start 4 to 7 days after exposure and most resolve within the acute phase of the disease. Although the acute phase lasts approximately 2 weeks, joint pain can persist for Title: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity", "Passage: Included patients were from the region of Emilia-Romagna in north-east Italy suspected to be infected with CHIKV since they showed symptoms such as myalgia, severe back and joint pain, headache, and skin rash. Collaboration with the regional microbiology reference laboratory of Bologna University and the Department of Infectious and Parasitic Diseases of the National Institute of Health in Rome was initiated and identified the patients as having CHIKV. The clinical criteria was described as acute onset of fever and severe arthralgia not explained by other medical conditions. CHIKV infection was confirmed by one or more of the acute phase tests: Title: Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity", "Passage: following persistent joint pain and/or disease resolution. Blood samples were collected from 50 patients suffering from CHIKV infections during the 2007 Italian outbreak. Serum separated from whole blood was analyzed by cytokine bead analysis for 13 cytokines with the intention of determining a cytokine profile during CHIKV acute phase and disease convalescence. Three cytokine profiles emerged from our data: decreasing, increasing and no-trend.", "Title: Responding to the COVID-19 pandemic in complex humanitarian crises\nPassage: To mitigate the impact of COVID-19 on crisesaffected populations, governments and agencies will implement the familiar, global evidence-based approaches for combatting respiratory viruses. Respiratory hygiene is a highly effective public health intervention, supported by evidence demonstrating that the spread of respiratory viruses, such as SARS-CoV-2, can be prevented by hand hygiene, safe cough practice, and social distancing . Hand hygiene is a readily implemented behavior: the distribution of soap to households in humanitarian settings has been shown to increase handwashing by over 30% . Furthermore, hand hygiene is an avenue of agency for protecting one's own health, consistent with the Title: Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014", "Passage: Hand hygiene education in public facilities such as schools and kindergartens resulted in reduced risk of infection, and hand hygiene compliance in hospital settings reduced the incidence of in-hospital infections and, thus, reduced demand for hospital resources . Worldwide, handwashing and hand hygiene education programs have high priority in public health programs, in which role models such as healthcare workers and community members encourage hand hygiene. Institutional support for funded studies and interventions should be a top-priority agenda item in order to improve hand hygiene behaviors . Title: Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study", "Passage: Self-efficacy in preventing A/H1N1 influences hand hygiene but has little influence on social distancing. Formal health education messages that focus on enhancing the public's sense of their ability to protect themselves by adopting hygiene practices would seem to be the most effective to improve hand hygiene, but where the practice is already established, high levels of trust in these messages are not likely to significantly increase hand hygiene. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: Recall of key health messages was varied, however most participants were aware of hygiene self-efficacy measures such as hand washing, sanitiser use, covering of coughs and sneezes, and staying at home. This was particularly strong in one of the Pacific Peoples groups and for many appeared to be translated into action.", "Title: Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant\nPassage: Streaks of Detrick 1, Detrick 2, and 1013 strains were grown for two days on TSA plates containing SBA.Bacterial cell mass was scraped using an inoculating loop from the streak and resuspended in PBS. Sporulation was evaluated by bright field phase-contrast microscopy. Phase-bright free sporesand phasedark vegetative cellswere counted. Five representative viewing fields were counted from each strain for each experiment. This experiment was completed in triplicate by repeating once per day over the course of three consecutive days. Title: Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant", "Passage: of the plot in each array along the y-axis. Each cell ratio value represents the average of two biological replicates for each strain. Plates PM01-PM10 contains single wells for each growth condition, while plates PM11-PM20 contain quadruplicate wells for each growth condition. Solid circle indicates wells containing sodium lactate; dotted circle indicates well containing L-serine at pH 4.5. The details of the 1920 growth conditions can be found in the first worksheet labeled ''All strain AUC data'' in Table S4 . B) Most significant phenotypes for each of the six test strains as compared to the 1942 strain. The phenotypes Title: Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant", "Passage: the strains sequenced for this study. Given the lack of original records, it is unclear whether the NRS-356 variant in this study might have passed through Camp Detrick and been returned to the University of Wisconsin. However, given the date on the label and the general secrecy of operations at Camp Detrick during the Second World War we consider this possibility unlikely. Title: Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant", "Passage: The first seven BGstrains listed in Table 1 were streaked for single colonies on BHI plates and incubated at 33uC overnight, followed by subculturing a second time under the same conditions. Subsequently, cell suspensions were prepared according to Biolog specifications, with OD readings ranging between 0.35-0.45 at 600 nm. Biolog phenotypic microarray plates PM1 through PM20, were inoculated according to the manufacturer's specifications, and incubated at 37uC for 72 hours. Readings were taken every 15 minutes, and data processed by OmniLog Phenotype Microarray File Management/Kinetic Plot and Parametric modules. Two biological replicates of the experiment were conducted for each strain.", "Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia\nPassage: Influenza viruses and picornavirus were the most commonly identified viruses, found in 38 and 22 patients, respectively. In nine patients, more than one virus was identified. In the 21 patients having undergone mPCR in both NP swabs and LRT specimen, the mPCR were discordant in ten patients, including eight patients with a NP mPCR positive and a LRT mPCR negative and two patients with a NP mPCR negative and a LRT mPCR positive. Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia", "Passage: The four study groups did not differ in terms of demographics, comorbid conditions, chronic immunosuppression, HCAP factors, incidence of transfer from another ward, and antibiotics before referral . The microbiological investigations also were similar . S. pneumoniae was the predominant bacterium in both bacterial and mixed groups . Only one patient was infected with extended-spectrum betalactamase-producing Enterobacteriaceae. Fourteen patients were infected with intracellular bacteria, including L. pneumophila, C. pneumoniae and M. pneumoniae, but only two had a viral coinfection. Influenza viruses were the most commonly viruses in the viral group, whereas picornavirus and influenza viruses were equally predominant in the Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia", "Passage: A microbiological documentation was obtained in 144 patients. At least one bacterium was identified in 91 patients and at least one virus in 98 patients. Bacterial documentation was obtained in 56 patients who had not been exposed to antibiotics prior to referral, compared to 35 antibiotics-exposed patients . S. pneumoniae was the most commonly identified bacterium, found in 40 patients. Of these 40 patients, S. pneumoniae was cultured in blood in five patients. In 22 patients, more than one bacterial species was identified. Taken together, Pseudomonas aeruginosa and Enterobacteriaceae species were identified in nine patients of the bacterial group and Title: Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China", "Passage: M. pneumoniae was the most frequent pathogen among co-infections and multiple infections . M. pneumoniae plus IBV was the most frequent pathogen combination in dual respiratory infections , followed by M. pneumoniae plus AdV . M. pneumoniae plus AdV plus IBV was the most frequent pathogen combination among triple infections ( Fig. 1B", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: Decades of basic immunology research have provided a near-complete picture of the main armaments in the human antiviral arsenal. Nevertheless, this focus on mammalian defences and pathologies has sidelined examination of the types and roles of viruses and antiviral defences that exist throughout our biosphere. One case in point is the CRISPR/Cas antiviral immune system of prokaryotes, which is now repurposed as a revolutionary gene-editing biotechnology in plants and animals. 11 Another is the ancient lineage of nucleocytosolic large DNA viruses , which are emerging human pathogens that possess enormous genomes of up to several megabases in size encoding hundreds Title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus", "Passage: genome during viral infection. In this line, it has been reported that CRISPR system introduced into host cells during Adenovirus and HSV replication can indeed robustly stimulate DNA breakages in the targeted genomes with high frequency 26 . This discrepancy could be possibly due to the application of TK gene inhibitors in our experiments to prevent WT viruses outgrow the gene deletion viruses. Title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus", "Passage: to target and inhibit hepatitis C virus, a ssRNA virus 31 . It is conceivable that with the advances in this dynamic research field, CRISPR/Cas system could be very possibly employed to develop anti-RNA virus vaccines. Moreover, as recombinant PRV and HSV are extensively exploited for neural circuit tracing, our strategy could also significantly simplify the recombinant viral tracer engineering and could thus contribute to neuroscience research as well 32 . Title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus", "Passage: This strategy could also be applied to vaccine development against other DNA virus such as HSV, CMV, Adenovirus, VZV, Duck Hepatitis Virus , Bovine Herpesvirus and Epstein Barr Virus . Yet the CRISPR/Cas9 system is mostly applied in DNA editing, accumulating data suggest that this versatile technology could also work effectively in the RNA world. O'Connell et al. demonstrated that trans-complementation of protospacer adjacent motif presenting oligonucleotides can indeed stimulate site-specific targeting and cleavage of ssRNA by Cas9 endonuclease 30 . Recently, Francisella novicida Cas9 has been shown to have the capability of targeting endogenous bacterial RNA and was engineered", "Title: Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury\nPassage: an enhanced sensitivity to detect eosinophils in these lung tissue sections. Specifically, evaluations of the lungs of control subjects using EPX-mAb immunohistochemistry revealed a >40-fold increase in the ability to detect tissue infiltrating eosinophils relative to H&E staining . Title: Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury", "Passage: elevated level of eosinophil degranulation representing \u22653 areas of granule protein release that again is <10% of the field of view. Level 2a: Significant level of eosinophil degranulation that includes 10-50% of the field of view. Level 2b: Significant level of eosinophil degranulation that includes extracellular release of EPX, enucleated eosinophils , and/or the presence of free granules . The extent of degranulation represents >50% of the field's total area. Scale bar = 50 \u03bcm. Title: Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury\nPassage: disease progression in these subjects was such that nineteen of the twenty patients received corticosteroid therapy during their course of treatment. Title: Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury", "Passage: group of ALI patients, the collective group also evidenced a >2-fold increase in the level of eosinophil degranulation compared to control subjects . More importantly, quantitative assessments of degranulation based on EPX-mAb immunohistochemistry revealed that ALI patients surviving their hospitalization also displayed significantly higher levels of degranulation compared to non-surviving patients .", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Of note is that Ae. aegypti has most likely been established in North America for over 300 y, while Ae. albopictus has been in many areas of the US, since 1985, primarily in Florida and since then has expanded its range in the country. Reiskind et al. set out to determine if Ae. aegypti and Ae. albopictus mosquitoes captured in Florida were susceptible to CHIKV infection by a La Reunion isolate . Each mosquito tested was highly susceptible to infection by a full-length infectious clone of the La R\u00e9union Island isolate, CHIKV LR2006 OPY1 strain. Even though the Ae. albopictus Title: Dengue Fever, Hawaii, 2001\u20132002", "Passage: In entomologic surveys conducted during the outbreak, Ae. albopictus was present in all 29 communities surveyed on Oahu, Maui, Molokai, and Kauai, but no Ae. aegypti were found at any site. In drier areas, on the leeward sides of the islands, container indices were high , but landing rates were generally low. However, in Nahiku, a small community in densely vegetated woodland near Hana, Maui, that was heavily affected during the outbreak, adult Ae. albopictus populations were high, with landing rates of 70 to 90 mosquitoes per person in 5 minutes. In the surveys conducted at 300 sites in 2002, Title: The interconnected and cross-border nature of risks posed by infectious diseases", "Passage: In Europe, the climatic conditions have been permissive enough to enable Ae. albopictus to gradually expand from its introduction in Italy, where it arrived in 1990 . Today, Ae. albopictus is established in many regions of the Mediterranean Basin, including in Spain, France, Italy, Croatia, and Greece. In addition, the mosquito has been introduced to regions as far north as Germany, the Czech Republic, and Slovakia. 4 Models based on the known climatic determinants of Ae. albopictus suggest that many more areas of Europe could be suitable habitats for the mosquito as well as for Chikungunya transmission, with some regions Title: Dengue Fever, Hawaii, 2001\u20132002\nPassage: Ae. albopictus was the vector responsible for the 2001 Hawaii outbreak. Both entomologic surveys support that Ae. albopictus is ubiquitous, often common on all the islands, whereas Ae. aegypti is restricted to a few small foci on the relatively sparsely inhabited island of Hawaii.", "Title: Metagenomic Assay for Identification of Microbial Pathogens in Tumor Tissues\nPassage: PCR amplification using universal 16S rRNA primers, followed by amplicon sequencing, is the most widely used strategy for exploring investigations in associated microbiomes and provides an effective discovery tool . However, this will work only for bacterial species with amplicons that survive population PCR but not for viruses or eukaryotic microorganisms. 16S rRNA sequencing can also be used to screen large sets of samples but may have difficulty in discriminating between strains or reporting the presence of genomic variants or pathogenicity factors. Deep sequencing of the total DNA from a sample can certainly identify bacterial, viral, and other microbiome members Title: Using noninvasive metagenomics to characterize viral communities from wildlife", "Passage: viral detection in PCR-based studies and it is reasonable to assume the same in metagenomic studies. Title: Using noninvasive metagenomics to characterize viral communities from wildlife\nPassage: Finally, although it was not the focus of our study, we also detected reads from vertebrates, protozoa and bacteria , suggesting that with appropriate bioinformatic modifications, shotgun metagenomic data generated using our protocol could simultaneously shed light on host genetics, diet, other non-viral pathogens and commensal microbes. As metagenomics becomes an ever more popular and powerful tool for viral ecology, use of standardized methods such as those developed here will be crucial for comparative insights from diverse host species and environments. Thanks also to Julio Benavides for advice on the subsampling analyses. Title: Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance", "Passage: As the cost of Next Generation Sequencing has decreased this technology has become available for routine use 14 . The technology is applicable for complete sequencing of entire microbial communities 15 and directly on clinical samples 16 . It has also been argued that the technology might have major implications for especially developing countries where NGS as a one-fits-all tool could enable these countries to avoid the establishment of more complex diagnostic methods as those already established in developed countries 14 . NGS combined with novel hot-spot sampling points could potentially provide simultaneous diagnosis of all known pathogens and resistance", "Title: 1918 Influenza: the Mother of All Pandemics\nPassage: Initial genetic characterization of the 1918 \u201cSpanish\u201d influenza virus. Title: 1918 Influenza: the Mother of All Pandemics\nPassage: 12. Reid AH, Fanning TG, Hultin JV, Taubenberger JK. Origin and evolution of the 1918 \u201cSpanish\u201d influenza virus hemagglutinin gene. Title: 1918 Influenza: the Mother of All Pandemics\nPassage: Characterization of the 1918 \u201cSpanish\u201d influenza virus neuraminidase gene. Proc Natl Acad Sci U S A 2000;97:6785\u201390. Title: 1918 Influenza: the Mother of All Pandemics\nPassage: Characterization of the 1918 \u201cSpanish\u201d influenza virus matrix gene", "Title: Molecular Detection and Epidemiological Features of Selected Bacterial, Viral, and Parasitic Enteropathogens in Stool Specimens from Children with Acute Diarrhea in Thi-Qar Governorate, Iraq\nPassage: of individual studies should not be taken as implying that the totality of evidence supports no effect. Hence, it is recommended that mothers should always be encouraged to wash their hands following the use of a toilet, cleaning the child's bottom after defecation, and before feeding the child, as inadequate hand hygiene can transfer contamination to surfaces and foods in the home . Title: Molecular Detection and Epidemiological Features of Selected Bacterial, Viral, and Parasitic Enteropathogens in Stool Specimens from Children with Acute Diarrhea in Thi-Qar Governorate, Iraq", "Passage: Effective hand hygiene is essential to prevent the spread of microbes from person to person and reduce cross-contamination from hands to food . In the present study sample, the likelihood of Entamoeba spp. detection in children belonging to caregivers who reported always washing hands after cleaning child defecations was significantly lower . However, our study data could not conclude a relationship between caregivers' hygienic practices and occurrence of the other frequently detected bacterial and viral pathogens . It is possible that caregivers' hygienic practice is a limited route of exposure, compared to other sanitary and environmental routes, and, hence, it Title: Gatekeepers of health: A qualitative assessment of child care centre staff's perspectives, practices and challenges to enteric illness prevention and management in child care centres", "Passage: When staff defined diarrhea, they often used visual and sensory based descriptions like: \"uncontained\", \"out of the diaper\", \"running down their legs\". Staff used these cues to take action. However, staff definitions or descriptions of diarrhea were not the same; there was a level of ambiguity and uncertainty and they experienced a dilemma in determining whether a child was ill or not. The staff described two reasons for this uncertainty: Title: Gatekeepers of health: A qualitative assessment of child care centre staff's perspectives, practices and challenges to enteric illness prevention and management in child care centres\nPassage: Staff: We tend to be a little proactive, well just yesterday we had one case of diarrhea and today we sent a child home with vomiting, so that room has now been totally disinfected with Virox.", "Title: Evidence for Novel Hepaciviruses in Rodents\nPassage: also by human activities such as hunting of bats as bushmeat and human invasion of remote habitats . Several rodent species are also in focus as potential virus reservoirs, as they constitute habitat generalists and follow human civilization, providing opportunities for virus transmission . Even though rodents form smaller social groups than bats, some rodent species have a high population turnover, which should enable efficient maintenance of viruses through the continuous replenishment of susceptible individuals . Among terrestrial mammals, rodents and bats together constitute about two thirds of the 5,487 known mammalian species . Screening of wild mammals with a Title: Mammarenaviral Infection Is Dependent on Directional Exposure to and Release from Polarized Intestinal Epithelia", "Passage: Epidemiological observations in West Africa indicate that the ingestion of food contaminated with excreta of infected M. natalensis is one of the natural mechanisms of LASV transmission to humans . Up to 45% of individuals living in some LASV endemic regions in Western Africa can be seropositive to the virus; and if re-infection occurs, seropositive individuals can protect themselves from disease onset. However, seronegative individuals may also be protected from disease, due to protection associated with cell-mediated immunity . This implies high prevalence into endemic populations; however, the precise mechanisms behind this phenomenon are unknown. In NHP studies of arenavirus Title: Host-Driven Phosphorylation Appears to Regulate the Budding Activity of the Lassa Virus Matrix Protein", "Passage: The Mammarenavirus genus is comprised primarily of rodent-borne viruses, several of which are capable of causing severe hemorrhagic fever syndromes in humans . Lassa virus , the causative agent of Lassa fever, is carried primarily by the multimammate rat, Mastomys natalensis, but other carrier rodents have been identified recently . LASV infects up to an estimated 300,000 people each year in western Africa following exposure to rodent excreta or through hunting and consumption of infected rats . Lassa virus can also spread person-to-person through direct contact with infected bodily fluids, and this pattern of transmission has occurred repeatedly in hospital Title: Host and viral traits predict zoonotic spillover from mammals", "Passage: highest for Bunya-, Flavi-and Arenaviruses in rodents; Flavi-, Bunyaand Rhabdoviruses in bats; and Herpesviruses in non-human primates . Of 586 mammalian viruses in our dataset, 263 have been detected in humans, 75 of which are exclusively human and 188 zoonotic-defined operationally here as viruses detected at least once in humans and at least once in another mammal species . The proportion of zoonotic viruses is higher for RNA than DNA viruses. The observed number of viruses per wild host species was comparable when averaged across orders, but bats, primates, and rodents had a higher proportion of observed zoonotic viruses compared", "Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: At 24:00 on 26 January 2020, the National Health Commission of the People's Republic of China has recorded a total of 2744 confirmed cases of pneumonia with 2019-nCoV infection from 30 provinces , including 461 severe cases and 80 deaths. A total of 51 cases have been cured and discharged. At present, 5794 suspected cases were recorded, 32,799 with close contacts to the confirmed patients have been tracked, 583 people were released from medical observation that day, and 30,453 people were still undergoing medical observation. A total of confirmed cases were reported from Hong Kong, Macao and Taiwan of China: Title: Clinical review: Primary influenza viral pneumonia", "Passage: Bacterial co-infection, though uncommonly reported in the early stages of the 2009 H1N1 pandemic, may be more prevalent than initially thought. A recent analysis of lung specimens from 77 fatal cases of pandemic H1N1v 2009 infection found a prevalence of concurrent bacterial pneumonia in 29% of these patients . The most common coinfecting bacterial pathogens were pneumococcus, Staphylococcus aureus, and Streptococcus pyogenes, with a median duration of illness of 6 days . Title: Clinical review: Primary influenza viral pneumonia", "Passage: age versus 6% to 9% of the adults 18 to 64 years of age and none of the children . Influenza attack rates during seasonal epidemics vary between 10% and 20% but can be much higher during pandemics. For example, an analysis of the pandemic 2009 H1N1 influenza A outbreak in La Gloria, Veracruz, found clinical attack rates of 29% in adults older than 15 years and 61% in children younger than 15 years of age . However, these rates may be different in geographic areas of low population density. Title: Pneumonia among adults hospitalized with laboratory-confirmed seasonal influenza virus infection\u2014United States, 2005\u20132008\nPassage: Patients with pneumonia ] were significantly more likely to receive influenza antiviral therapy than patients without pneumonia ; P <0.01].", "Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study\nPassage: five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 \u00d7 10 copies in three patients and was Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Flulike symptoms, such as fever, cough and little sputum, were commonly observed at the onset of illness. All patients presented with a high fever, with a mean body temperature of 39.5\u00b0C , which persisted for 8 days . Productive cough was observed in two patients. Dull substernal chest pain and rash were also observed in two patients. All patients had dyspnea. The mean time from onset to dyspnea was 5 days . After the onset of dyspnea, patients usually progressed to respiratory failure or hypoxemia. The mean time from onset to ICU admission was 9.6 days . All patients had Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: Flulike symptoms, such as fever, cough and little sputum, were commonly observed at the onset of illness. All patients presented with a high fever, with a mean body temperature of 39.5\u00b0C , which persisted for 8 days . Productive cough was observed in two patients. Dull substernal chest pain and rash were also observed in two patients. All patients had dyspnea. The mean time from onset to dyspnea was 5 days . After the onset of dyspnea, patients usually progressed to respiratory failure or hypoxemia. The mean time from onset to ICU admission was 9.6 days . All patients had Title: Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study", "Passage: 1 \u00d7 10 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Vigilance remains important for containment since MERS-CoV is a virus with a genetic makeup that has been observed for only three years and is not stable. Among all humans reported to be infected, nearly 40 % have died. Continued laboratory testing, sequencing, analysis, timely data sharing and clear communication are essential for such vigilance to be effective. Global alignment of case definitions would further aid accurate calculation of a case fatality ratio by including subclinical case numbers. Whole genome sequencing has been used extensively to study MERS-CoV travel and variation and although it remains a tool for experts, it appears Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: With the emergence of MERS-CoV in the Middle East, a preparedness plan was developed that included a surveillance plan, laboratory testing, and contact tracing guidance. Infection control guidance was developed for use in health care settings and traveler guidance was developed for the public.6 The US Centers for Disease Control and Prevention distributed MERS-CoV polymerase chain reaction test kits to state health departments. Two cases were imported into the United States. Contacts were traced, including household, hospital, and airline contacts. No secondary cases were identified in the United States. MERS-CoV was thought to be severe and control measures relied on Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: ere is no specific treatment for MERS-CoV. Like most viral infections, the treatment options are supportive and symptomatic . At present, no vaccine exists for preventing the infections of MERS-CoV. e CDC indicated that preventative actions should be taken for any type of respiratory illness . Such actions include washing hands with water and soap for around 20 seconds or using hand sanitizers with alcohol if no water is available. One must cover their nose and mouth during instances of sneezing and coughing with a tissue and avoid touching the mouth, nose, or eyes with their hands until washed properly. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5", "Title: Estimating the number of infections and the impact of non-\nPassage: 2 Results Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: 28 and 60 days after enrollment. Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: FLU003. Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: treatment .", "Title: Reverse Engineering Provides Insights on the Evolution of Subgroups A to E Avian Sarcoma and Leukosis Virus Receptor Specificity \u2020\nPassage: using a His-tagged, secreted form of the RCASBP envelope glycoprotein expressed using chicken DF-1 cells and purified. The bonds to C11 and C12 could not be assigned further. The free cysteine is labeled C2. The N-linked glycosylation sites actually containing carbohydrate are marked in blue. The unglycosylated sites are underlined, N8 and N13. For reference, the hypervariable regions are marked: hr1 in green boxes; hr2 in an orange box; and vr3 in a pink box. Title: Is countries\u2019 transparency associated with gaps between countries\u2019 self and external evaluations for IHR core capacity?\nPassage: and outcome of JEE 2.0. Title: Is countries\u2019 transparency associated with gaps between countries\u2019 self and external evaluations for IHR core capacity?", "Passage: We applied the methodology developed and used in previous study which indicating the important role of transparency in the gap of reporting timeliness in infectious disease . While Systemic Rapid Assessment is a framework includes External contexts as socialenvironmental factors and health-specific elements which echoing the element of national responsibilities required by IHR 2005, it was consulted to be the conceptual and analytical guidelines for the evaluation of health systems and infectious disease control programs . Therefore, we collected transparency data and measurements based on this framework for further analysis. Title: Reverse Engineering Provides Insights on the Evolution of Subgroups A to E Avian Sarcoma and Leukosis Virus Receptor Specificity \u2020", "Passage: One genetic selection strategy has taken advantage of the fact that secreted forms of the ASLV receptors potently bind the Env trimer to compete with cell-associated receptors to block infection. The ASLV receptor immunoadhesins, the extracellular domain of an ASLV receptor fused to the mouse IgG domain , specifically bind only the concomitant ASLV glycoprotein subgroup to pressure the glycoprotein to acquire mutations that significantly reduce the binding affinity to the receptor immunoadhesin and possibly alter and/or broaden the ability of the variant to use other cell surface proteins as functional receptors.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: For viral vectors, the impact of cell-mediated immunity was more pronounced, and as depicted in Table 2 , almost always resulted in a reduction in the subsequent immune response. Presumably this is because viruses will induce neutralizing antibody on the first dose, and in subsequent doses this antibody will limit the number of transduced cells, therefore limiting the responses. This is particularly a problem with a common viral vector such as Ad, where a large proportion of the population will have immunological memory against common serotypes . As these authors conclude, it will be possible to utilize such vectors only Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Similarly studies of L. monocytogenes and the effects of preexisting immune responses indicate conflicting results. A study by Bouwer et al. indicates that pre-existing immune responses against the Listeria vector do not diminish immune responses against the delivered heterologous antigen, and a similar study by Starks et al. also concluded that prior exposure of mice to the empty Listeria vector did not influence anti-cancer immune responses when a similar mutant was used as a carrier of a melanoma cancer antigen. Similar findings were reported by Whitney et al. in rhesus macaques in which L. monocytyogens was used as a carrier Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: as such, when a vaccination is delivered, an anamnestic response to the Salmonella antigens will be induced . This will theoretically reduce the exposure of the heterologous antigen to the immune system, as the vector is rapidly cleared. Surprisingly, as will be seen in some of the examples given below, this can have results that differ depending on the magnitude of the response to the vectored antigen. Similarly, for virally vectored antigens, the existence of pre-existing immunity to the vector will restrict delivery of the virus into cells, thereby effectively reducing the dose of the vectored antigen. Again, this might", "Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: Text: Human bocavirus 1 , which belongs to family Parvoviridae, was firstly identified in respiratory secretions of children with respiratory tract disease in 2005 . HBoV1 has been confirmed as an important respiratory pathogen and is found in respiratory infections in children and adults worldwide. The prevalence of HBoV1 nucleic acid detection varies from 1.5 to 33% in patients with acute respiratory illness , according to different studies . Serological and nucleic acid test results are generally consistent , showing HBoV1 infection is very common. HBoV1 can cause both upper respiratory illness and lower respiratory illness . Infection with HBoV1 Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: Two hundred forty-eight of 11,399 patients tested positive for HBoV1 infection. Of the HBoV1-positive patients, 112 were co-infected with other pathogens, most frequently with RSV . The median age was 1 year . The male-to-female ratio was 2.54:1 in HBoV1-positive patients and 1.81:1 in HBoV1-negative patients . Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region", "Passage: To clarify the age distribution of HBoV1, patients were divided into seven age groups; 0-3 months, 4-6 months, 7-12 months, 1-2 years, 3-5 years, 6-10 years and 11-14 years old. There was a significant difference in the prevalence of HBoV1 in patients in different age groups and the peak prevalence was found in patients aged 7-12 months . Title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region\nPassage: and analyzed immediately or stored at \u2212 80\u00b0C before analysis, as described previously .", "Title: Viroporins in the Influenza Virus\nPassage: In summary, most information available for influenza viroporins is centered around AM2, followed by BM2. For the latter, structural data are increasingly available, but protein-protein interaction data studies comparable to AM2 are lacking. Viroporins in ICV and IDV have attracted much less interest, concomitant with their lower virulence in humans and biomedical relevance. Nevertheless, their mode of action, and those of lesser known viroporins, can help to better understand ionic transport across membranes. Title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?", "Passage: As obligate intracellular parasites, viruses have evolved a myriad of strategies to manipulate the host cell environment to one that is conducive for virus replication. Research over recent decades has identified a group of virus-encoded proteins able to mediate the passage of ions and solutes across cellular membranes, termed viroporins . The majority of viroporins described are small and contain one or two transmembrane domains , although a small number of larger viroporins have been shown to encode up to three putative TMD . Whilst high-resolution structural information is currently only available for a limited number of viroporins , a Title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?", "Passage: the Flaviviridae, Picornaviridae, Retroviridae, Coronaviridae, Reoviridae and Paramyxoviridae . To date, the overwhelming majority of viroporins have been identified in RNA viruses. However, given the myriad of cellular processes that they are able to modulate, it is logical to assume that all viruses might benefit from encoding such a protein. Recent findings have now identified proteins that exhibit a number of viroporin characteristics encoded by members of the Polyomaviridae and Papillomaviridae. This review will summarize our understanding of these putative viroporins, describe their known functions and attempt to highlight how possible ion channel activity may aid the life cycles of Title: Viroporins in the Influenza Virus\nPassage: from .", "Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis\nPassage: The simultaneous outbreaks of influenza in humans and pigs during the 1918 pandemic naturally raised questions about whether the virus had transmitted from pigs to humans, or humans to pigs. At the time, Koen noted that the flu outbreaks appeared to represent a novel disease in pigs, whereas humans had a long history of influenza pandemics, which suggested that humanto-swine transmission was more likely. Almost a century later, the reconstruction of a 1918 virus from human tissues preserved in Alaskan permafrost and autopsy blocks indicated that the virus's genes appeared to have avian origins . But this did not end Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: Overall, the most parsimonious explanation is that the genes of the 1918 virus transmitted largely from birds to humans at the start of the pandemic, and from humans to swine once the pandemic was widespread in humans, with no role played by swine in the origins of the human pandemic . In addition to Koen, there is a reference to an infection with influenzalike disease in swine near the China-Russia border during the second global wave of the pandemic during October 1918 and an independent description of influenza in European swine in 1918 by Altmann Aladar, a Hungarian veterinarian . Title: Lessons learned from the 1918\u20131919 influenza pandemic", "Passage: The current international strain of novel H1N1 virus discovered in Mexico is derived from two unrelated swine viruses, one associated with a fourth generation of the 1918 human infl uenza virus with which acts to recombine the viruses and its progeny . Essentially the virus continues by shuffl ing its eight genes in the avian reservoir to eventually be passed to swine and other mammals before the encounter with humans. Seldom are there transfer of infl uenza between humans and avian. Pigs act as the \"transformers or converters\" for the various infl uenza viruses and let loose the world new Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: coincidence if not suggesting a close relation between the two conditions\" . Confirmation that influenza was circulating in US swine was achieved in 1931 when Richard Shope isolated the first influenza virus from pigs . Two years later, the H1N1 virus was isolated from humans . It was later demonstrated that sera from humans infected with the 1918 pandemic virus could neutralize the swine virus .", "Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders\nPassage: Thus it is apparent that obesity and inflammation play major role in the development of T2DM and its associated complications and therefore therapeutic regimens may be targeted towards ameliorating these effects. The control of obesity is recommended in the MedlinePlus 159 site also. Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders", "Passage: Hyperglycaemic conditions in late stages of diabetic individuals include well known microvascular complications and macrovascular complications . Even these complications evidently are polygenic disorders . Inflammation could lead to vascular calcification in association with atherosclerosis 31 . Hepatokines such as Fibroblast growth factor 21, Fetuin A and selenoprotein P are also implicated in the development of atherosclerosis 32 . It is evident that the complications arising from T2DM are also multifactorial and could be further governed by gene-environment interactions. Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders", "Passage: Among the risk factors considered in this work, are obesity, inflammation, stress and diet and their interactions with the genes of T2DM associated complications. The major share of differentially expressed genes in T2DM patients as observed here is contributed by pancreas tissue followed by adipose and skeletal muscle tissues. Obesity is clearly a dominant risk factor interacting with the genes of T2DM complications followed by inflammation, diet and stress to variable extents. These results indicate the likelihood of developing a complication given the tissue of measurement of differentially expressed genes and the contributing risk factor. However, it is to be Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders", "Passage: In Adipose tissue, obesity topped the list with the number of DEG associated with nephropathy, atherosclerosis, whereas in neuropathy and retinopathy, stress and inflammation are at the top and in cardiovascular complication, diet and inflammation topped the list .", "Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs\nPassage: The chemiluminescent enzyme-linked immunosorbent assay was performed by detecting EBOV with the anti-EBOV VP40 antibody followed by staining with the horseradish peroxidase -conjugated goat anti-mouse secondary antibody . Chemiluminescence was quantified using Pico Chemiluminescent Substrate and a plate reader . Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: In addition to the fluorescent assay, we also implemented a CELIA using an HRP-labeled antibody, which amplified the signal and increased the sensitivity of virus detection. As expected, the CELIA showed an improvement in the quality of data sets compared to the fluorescent assay. S/N ratio and Z' factor were in an acceptable range as early as 24 hpi with the lowest virus input detected at an MOI of 0.1. An EC 50 could also be determined at this time point. At 48 or 72 hpi, the two fluorescent read outs were similar to the chemiluminescent read out. Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: per experiment, two plates for detecting inhibition of EBOV, and one mock plate for determining drug cytotoxicity. After 1 h of predilution and transport to the BSL4 laboratory, 50 \u03bcl of virus at the desired MOI was added to cells. At 48, 72 or 96 hpi, assay plates were fixed at final concentration of 10% NBF for 24 h before transferring to a BSL-2 lab for staining. Infected cells were detected as described above. To further confirm the accuracy of assays with high background, chemiluminescence assay was performed afterwards. Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: Fluorescence was detected by two different read outs and each technique has its advantages. The plate reader will measure the average fluorescence across the whole well. Readings are quick and conducive to handling large numbers of plates during screening. However, the quality of the cell layer cannot be monitored. HCI provides images of 1 or more fields of each well, and a nuclear stain can be added in parallel to indicate the viability of the cell layer. In the assay development phase, this tool is especially useful in identifying conditions that will ensure a healthy cell layer or identify issues", "Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana\nPassage: A total of 72 HCWs indicated media especially radio as the main source of information when asked where they first heard of EVD. This was significantly more than other sources . When asked which biosafety level laboratory is required to test sample from suspected patient with EVD, a total 19 indicated BSL-3 of which 11 were Medical Doctors, while 8 and 1 were Nurses and Physician Assistants, respectively. A further 76 , of which 9 were doctors, 62 Nurses When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% could correctly Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: A total of 92 HCWs surveyed indicated they were not adequately trained to handle an EVD suspected case. When asked to rate their competence in handling an EVD suspected patient, 18.81% indicated they had little confidence and competence, while 6.93% indicated they were extremely confident to handle a suspected case of EVD . Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: We administered a face-to-face questionnaire using an adapted WHO and CDC Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. RESULTS: A total 92 HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% could correctly identify the right disinfectant = 28.52, p = Title: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana", "Passage: The results of this survey showed that more than half HCWs indicated that their facilities were not ready to handle EVD cases. Nearly 92% indicated they were not adequately trained to handle an EVD suspected case and it is not surprising that less than 50% indicated they would willingly attend to a suspected patient. Moreover, nearly a third of HCWs would also want insurance for themselves and their families in case they were infected with EVD.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: naturally occurring pattern following the evolutionary characteristics typical of CoVs, it is highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species are the most revealing signs that SARS-CoV-2 evolved by natural evolution. A search for an intermediate animal host between bats and humans is needed to identify animal CoVs more closely related to human SARS-CoV-2. There is speculation that pangolins might carry CoVs closely related to SARS-CoV-2, but the data to substantiate this is not yet published . Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Currently, there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin. Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV was recently reported, which shared \u223c96% homology with the SARS-CoV-2 . However, as we know, the human SARS-CoV and intermediate host palm civet SARSlike CoV shared 99.8% homology, with a total of 202 single-nucleotide variations identified across the genome . Given that there are greater than 1,100 nt differences between the human SARS-CoV-2 and the bat RaTG13-CoV , which are distributed throughout the genome in a Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Evolution is stepwise and accrues mutations gradually over time, whereas synthetic constructs would typically use a known backbone and introduce logical or targeted changes instead of the randomly occurring mutations that are present in naturally isolated viruses such as bat CoV RaTG13. In our view, there is currently no credible evidence to support the claim that SARS-CoV-2 originated from a laboratory-engineered CoV. It is more likely that SARS-CoV-2 is a recombinant CoV generated in nature between a bat CoV and another coronavirus in an intermediate animal host. More studies are needed to explore this possibility and resolve the natural origin Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Due to the elevated pathogenic activity of the SHC014-MA15 chimeric virus relative to MA15 chimeric virus with the original human SARS S gene in mice, such experiments with SL-SHC014-MA15 chimeric virus were later restricted as gain of function studies under the US government-mandated pause policy . The current COVID-2019 epidemic has restarted the debate over the risks of constructing such viruses that could have pandemic potential, irrespective of the finding that these bat CoVs already exist in nature. Regardless, upon careful phylogenetic analyses by multiple international groups , the SARS-CoV-2 is undoubtedly distinct from SL-SHC014-MA15, with >6,000 nucleotide differences across", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: Rotavirus infection is the most common cause of viral gastroenteritis among children; however, parents of infected children also often become ill and as a result rotavirus is the second most common cause of gastroenteritis in adults . Studies in human volunteers have shown that infection with rotavirus causes diarrhea, results in shedding of the virus and a rise in antibody anti-virus titer after infection . Additionally, astroviruses infections are common, accounting for about 10% of all sporadic diarrhea cases . Astrovirus has been isolated from diseased people, filtrated and administered to healthy individuals after which in some of the volunteers Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Caliciviruses, in particular noroviruses, are the most important cause of epidemic, non-bacterial gastroenteritis worldwide, affect both adults and children, and account for 40 to 50% of all foodborne gastroenteritis in the United States . Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Acute viral gastroenteritis is an important and often unappreciated cause of morbidity and mortality worldwide. Nearly all children have experienced at least one rotavirus infection by age five. Rotavirus accounts for approximately two million hospitalizations and between 350,000 and 600,000 deaths in young children each year . Astrovirus has been found by several studies to be an important cause of acute gastroenteritis in young children; a prevalence study in the United Kingdom found that over 70% of five year-olds had antibodies to the virus . Astrovirus has also been cited as an important cause of gastroenteritis in elderly populations . Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond", "Passage: Text: The gastrointestinal tract is a vulnerable organ for infections as there is constant contact with the outside, mainly via the oral route. Inflammation of the stomach and the intestines can cause nausea, vomiting and diarrhea. Gastroenteritis is responsible for two to three million deaths each year, making it one of the most common causes of mortality . Mainly children in developing countries, but also immuno-compromised individuals in developed countries, suffer from diarrhea. While bacterial and parasitic gastrointestinal infections are declining as a result of proper disposal of sewage and safe drinking water, viral gastroenteritis is not declining in developing", "Title: Vaccines and Therapeutics Against Hantaviruses\nPassage: Next, they developed HFRS candidate DNA vaccines expressing HTNV or PUUV Gn and GC genes and evaluated them in an open-labeled single-center phase 1 study. The results showed that HTNV and PUUV DNA vaccines prepared by electroporation were safe. When mixed together, the response to PUUV was greater than that to the HTNV DNA vaccine, and both DNA vaccines had immunogenicity . Title: Quantification of Hantaan Virus with a SYBR Green \u2160-Based One-Step qRT-PCR Assay", "Passage: HTNV is an enveloped virus with a single-stranded, negative-sense RNA genome. HTNV was the first hantavirus described and was isolated in 1978 . The virion encloses three gene segments named L , M , and S , which encode different proteins . The L segment encodes an RNAdependent RNA polymerase, the M segment encodes two glycoproteins, Gn and Gc, and the S segment encodes a nucleocapsid protein . Variation in the S and M segments may alter the virulence and antigenicity of hantaviruses . The transmission pathway of hantavirus within rodents and from rodents to humans includes inhalation of aerosolized Title: The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo", "Passage: In conclusion, HHT potently inhibited the viral replication of VSV, NDV, PEDV, HSV-1, and PRV; by comparison, HHT treatment moderately inhibited infection by AIV at the given doses. Furthermore, HHT-treated embryos, chickens, and piglets were less susceptible to viral infections of NDV, NDV, and PEDV. In addition, our preliminary results show that HHT antagonizes the phosphorylation level of endogenous and exogenous eIF4E in Vero and HeLa cells. The potent antiviral action of HHT is restricted to a number of classes of viruses; more details and clarification are still needed. Title: The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo", "Passage: optimal inhibitory activity, and completely inhibited viral infection. Finally, we studied whether HHT displays potent antiviral activity against NDV in chickens. As shown in Figure 2E ,F, 0.2 mg/kg HHT significantly decreased the mRNA level of NDV-NP in the liver and lung , and blood . HHT-treated animals did not exhibit a pathological change in tissues or symptoms such as diarrhea and drooping.", "Title: Estimating the number of infections and the impact of non-\nPassage: 03/0 25% 50% 753% 100% Title: Estimating the number of infections and the impact of non-\nPassage: representing between 1.88% and 11.43% ofthe population. The proportion of the population infected Title: Estimating the number of infections and the impact of non-\nPassage: Country % of total population infected Title: Estimating the number of infections and the impact of non-\nPassage: Norway 0.41%", "Title: Sounding the Alarm: Health in the Anthropocene\nPassage: Examples of phase changes are when water solidifies at freezing point or when we awaken. Social phase changes also occur, such as when an audience stands to applaud, or when a crowd in an uncovered stadium flees a violent storm. The onset of open hostility is another example of a social phase change. \"Eco-social\" changes can also occur, and are discussed below. Examples of Earth system threshold points and phase changes include the switch from ice ages to interglacial periods. Earth system scientists have identified many potential future tipping points, including in the climate system. Examples include the transition to Title: The interconnected and cross-border nature of risks posed by infectious diseases", "Passage: It is instructive to provide a few examples of how such risks are interconnected in the context of infectious disease. Literally, hundreds of examples from around the world could have been selected. One study identified 335 events leading to an emerging infectious disease between 1940 and 2004, identifying numerous infectious disease 'hotspots' across the globe \u00c1 areas in which a disproportionately high number of disease emergencies have concentrated . Western Europe is identified as one such hotspot, and as the region with which the authors of this chapter are most familiar, the examples below will be slightly biased towards Europe. Title: Using Satellite Images of Environmental Changes to Predict Infectious Disease Outbreaks\nPassage: rodent urine, feces, or saliva. The popular press may serve an important role in increasing awareness of a heightened health risk, which, in turn, promotes greater compliance with health advisories. Title: Chinese journals: a guide for epidemiologists", "Passage: an example of how a colonial legacy has left a language heritage that fosters internationalisation in this globalising world.", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Screening studies have shown that juvenile DCs are more often positive for virus or viral RNA while older DCs are more likely to be seropositive and RNA or virus negative . In adult DCs, MERS-CoV RNA has been detected among animals with pre-existing antibody, suggesting re-infection is possible . Viral loads among positive DCs can be very high and DCs have been found positive both when ill with URT respiratory signs or when apparently healthy . These findings indicate DCs host natural MERS-CoV infections. Furthermore, stored DC sera have revealed signs of MERS-CoV in DCs which date back over three Title: CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation", "Passage: Selective ablation of CD11c hi PDCA-1 int/lo DCs, but not CD11c int PDCA-1 hi pDCs, exacerbates JE. CD11c-DTR transgenic mice, which express diphtheria toxin receptor gene under control of a cloned Itgax promoter and thus allow conditional DC depletion upon DT injection, has been a milestone in DC research 20, 21 . However, along with contrasting results in the strength of DC subset depletion , it was recently reported that CD11c-DTR mice showed side effect such as systemic neutrophilia after DT injection to deplete CD11c + DCs 22, 23 . Because the majority of published literatures used 8-11 ng/g DT Title: Immunosenescence in vertebrates and invertebrates", "Passage: Virus-infected cell anti-tumor immunity . Thus, our knowledge of ageassociated changes to DCs is limited, but the rather subtle differences reported could have far-reaching \"knock-on\" effects, given that DCs are the central conductors at the innate-adaptive interface and that T cells, and therefore also B cells, are dependent for their function on these innate immune cells. Title: Oral administration of inactivated porcine epidemic diarrhea virus activate DCs in porcine Peyer\u2019s patches\nPassage: DCs are the most potent antigen-presenting cells that bridge innate and adaptive immunity in vivo . The study used IF analysis via dual staining with antibody specific to the DCs markers to detect DCs. SWC3a positive cells were stained red, MHC II positive cells were stained green, double positive cells were SWC3a + /MHC-II + DCs, which were stained yellow. Our results showed that the number of SWC3a + /MHC-II + DCs significantly increased in ileum after oral inactivated PEDV .", "Title: Frontiers in antiviral therapy and immunotherapy\nPassage: of proteins with unique and unknown functions. 12 Moreover, hundreds of human-and avian-infective viruses such as IAV strain H5N1 are known, but recent efforts indicate the true number may be in the millions and many harbour zoonotic potential. 13 It is increasingly clear that host-virus interactions have generated truly vast yet poorly understood and untapped biodiversity. Closing this Special Feature, Watanabe and Kawaoka elaborate on neo-virology, an emerging field engaged in cataloguing and characterising this biodiversity through a global consortium. 14 I predict these efforts will unlock a vast wealth of currently unexplored biodiversity, leading to biotechnologies and treatments that Title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?\nPassage: remains to be seen. Title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?", "Passage: of oligodendrocytes resulting in demyelination and development of PML, although it is not clear when the virus infects the central nervous system. Before the introduction of antiviral therapies to combat the progression to AIDS, PML was a prominent feature of the HIV phenotype. Since then, there has been a resurgence in PML cases as a wide range of immunosuppressant therapies are being applied to combat autoimmune diseases such as multiple sclerosis and aid in the acceptance of transplanted tissues . Links between JC and a range of human cancers have also been reported, although these are disputed . Title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?\nPassage: agnoprotein and VP4. These questions will remain unanswered until viroporin function is confirmed in SV40 agnoprotein.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV was found and characterized because of its apparent association with severe, and therefore more obvious, illness in humans; we were the canaries in the coal mine. Sero-assays and prospective cohort studies have yet to determine the extent to which milder or asymptomatic cases contribute to MERS-CoV transmission chains. However, transmission of MERS-CoV is defined as sporadic , intra-familial, often healthcare associated, inefficient and requiring close and prolonged contact In a household study, 14 of 280 contacts of 26 MERS-CoV positive index patients were RNA or antibody positive; the rate of general transmission, even in outbreaks is around 3 % Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: of \"contact\" during these interviews has been defined for one study . Despite this lack of clarity, the WHO consider that evidence linking MERS-CoV transmission between DCs to humans is irrefutable . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first WHO case definition defined probable cases of MERS based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract involvement. It also included roles for contact with a probable or confirmed case or for travel or residence within the Arabian Peninsula. If strictly adhered to, only the severe syndrome would be subject to laboratory testing, which was the paradigm early on . From July 2013, the revised WHO case definition included the importance of seeking out and understanding the role of asymptomatic cases and from June 2014, the WHO definition more Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and", "Title: Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets\nPassage: respiratory epithelial cells, which might reflect the fact that A/H5N1 AT virus was primarily adapted to transmit between ferrets. However, differences in infectivity in the human nasal respiratory epithelium between human and avian viruses were very clear, supporting the hypothesis that the nasal cavity could also be the preferred site for generation and expulsion of airborne transmissible influenza virus-laden particles in humans. Measuring the generation of influenza virus-laden particles upon breathing via the nose or the mouth separately would help in validating or inferring this hypothesis. Title: Characteristics of human infection with avian influenza viruses and development of new antiviral agents", "Passage: Epidemiology Three different subtypes of AIV have been confirmed as capable of infecting humans: H5, H7, and H9 . Humans can be infected by AIV primarily after their mucous membranes have come into direct contact with infectious secretions or excreta from infected birds or contaminated poultry products . The main infectious route of AIV seems to be via the upper respiratory tract and conjunctivae . Direct introduction to the lower respiratory tract may occur only after massive exposure, such as the culling operations of infected poultries . The role of infection through other routes remains to be explored. Title: Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets", "Passage: M illions of people have lost their lives due to influenza A virus epidemics and pandemics. Prevention and control of IAV infections are based on vaccination and treatment. However, a better fundamental understanding of IAV transmission could help to design additional appropriate intervention strategies, especially in health care settings. Transmission of IAVs between humans can occur via direct or indirect personto-person contact and through the air via respiratory droplets or aerosols. The relative contribution of each route of transmission is still under debate 1-3 , yet it is widely accepted that aerosol or respiratory droplet transmission is the key factor Title: Primate-to-Human Retroviral Transmission in Asia\nPassage: in any observable symptoms, SFV strains may differ in their capacity to infect or cause disease in humans. Finally, whether SFV can adapt in humans after transmission and potentially lead to disease needs to be examined.", "Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")\nPassage: In our additional data, respondents underrated the dangers of ordinary season flu, with 64% claiming that this killed under 100,000 worldwide . 26% of our European respondents wrongly believed that a vaccination for seasonal flu gave immunity against swine flu. The same percentage believed swine flu symptoms differ from those of seasonal flu. While only 3% had already obtained anti-viral drugs for use against swine flu, 32% claimed they would like to have these at home in case of infection. Few claimed they had stopped or reduced their eating of pork as a result of the pandemic. Title: Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment", "Passage: H1N1 viruses as the cause of seasonal influenza from 1957 to 1968. In 1968 a third pandemic was caused by an H3N2 virus, which replaced H2N2 viruses and continues to circulate in humans to the present day. Influenza A pandemics are associated with significant mortality, morbidity, and financial burden. Title: Long-term respiratory follow-up of H1N1 infection", "Passage: The first human infections with the new influenza A virus were confirmed in April 2009 in America, but the infection had been rapidly spreading around the world and in June 2009 World Health Organization declared a pandemic . WHO had advised countries in the northern hemisphere to prepare for a second wave of pandemic spread . To date, almost all countries in the world have confirmed a second wave of H1N1 virus . For this reason a working group of WHO member states agreed on a pandemic influenza preparedness framework . The reason for creating this framework began with the Title: Initial psychological responses to Influenza A, H1N1 (\"Swine flu\")", "Passage: In Europe only, we asked additional closed-ended questions about stopping or reducing eating pork as a result of the pandemic , and the precautionary desire for anti-viral drugs at home ). We asked about the mortality rate in ordinary, seasonal flu , as well as whether the symptoms of swine flu differed from seasonal flu, and whether seasonal flu vaccination provided immunity against swine flu . Throughout, statistical analysis for structured questions was through chi-square analyses and Pearson product moment correlation.", "Title: RNA-Dependent RNA Polymerase Speed and Fidelity are not the Only Determinants of the Mechanism or Efficiency of Recombination\nPassage: double mutants . The differences in outcome could reflect the differences in replication efficiency and/or a direct consequence of the substitutions in 3D-coding sequence on virus assembly or spread caused by changes to 3CD protein or 3D-containing precursor protein . After a productive infection, the exponential phase of genome replication by PV typically occurs between 2 and 6 h post-infection, with virus assembly occurring between 4 and 8 h post-infection. Release of infectious virus by lytic and/or non-lytic mechanisms can occur once virus is assembled and can persist for longer than 24 hours. Title: HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus", "Passage: Once in the cytoplasm, mRNAs undergo a CBC-mediated pioneer round of translation, which is important for the quality control of the transcript . CBC is then displaced from the m 7 G and mRNAs are activated by the eukaryotic initiation factor 4F complex and eIF4B . Thus, mRNA acquires a \"closed-loop\" structure, required for an optimal mRNA recruitment into the 43S pre-initiation complex . This conformation is achieved by the simultaneous binding of PABP -binding protein) and eIF4E to eIF4G . Title: HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus\nPassage: the ATP-binding cassette protein ABCE1, dissociates the post-TC into the 60S subunit, and the tRNA-and mRNA-bound 40S subunit . Title: HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus", "Passage: Eukaryotic translation is a complex process orchestrated by a wide range of players, including several protein factors and three classes of RNA , transfer RNA , and messenger RNA ). This process is comprised of three main steps: initiation, elongation and termination. Immediately after transcription, mRNAs are maturated and exported through the nuclear pores to the cytoplasm. Once in the cytoplasm, cap-dependent translation is initiated by the recruitment of the small ribosomal subunit , which scans along the mRNA until it finds an initiation codon. At this point, the large ribosomal subunit is engaged to decode the mRNA and assembles", "Title: Suffering a Loss Is Good Fortune: Myth or Reality?\nPassage: There were four potential limitations to our study. First, we only conducted a cross-sectional study in Study 3, whereas it would be preferable to measure Chikui likelihood earlier and then track the material and mental benefit of our participants years later. In the absence of a longitudinal study, our findings are suggestive but do not prove causality, and the following two questions therefore remain unaddressed: we are unable to confirm whether the correlation found in Study 2 means that it is the belief that boosts both financial and psychological well-being, rather than the reverse . Only a longitudinal study can Title: Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic", "Passage: A classic human study found that, in donors lacking neutralizing antibodies, pre-existing cytotoxic T-cell levels against influenza correlated with reduced virus shedding but not reduced symptoms after influenza virus challenge . Epidemiological studies of the 1957 pandemic, an H1N1 to H2N2 shift, suggested cross-protection, but these studies were too small for statistical significance or lacked laboratory confirmation of self-reported symptoms . A human challenge study found a correlation of CD4 memory with reduced illness duration, viral shedding, and symptom severity . Title: The Trojan Chicken Study, Minnesota", "Passage: Some of our study findings were unanticipated. We expected contamination proportions to vary by age, gender, and role because we expected these factors to affect the amount of contact with birds and handwashing behavior. However the rates did not vary by these variables. This finding could be due to the study's limited power to detect such differences. If the differences between those exposed and those unexposed were statistically significant , they might be consistent with studies that suggest that animal handlers practice better hygiene compared to nonhandlers in the same environment. Alternatively, animal handlers may engage in other behavior that Title: Chinese journals: a guide for epidemiologists", "Passage: results. However, subsequent studies found little evidence supporting this assertion. Pham et al. found that language bias led to an under-estimation of the protective effect of intervention in RCTs in complementary and alternative medicine systematic reviews but not in that of conventional medicine .", "Title: Self-assembly into virus\u2013like particles of the recombinant capsid protein of porcine circovirus type 3 and its application on antibodies detection\nPassage: of factors including storage conditions as well as the process design also influence the characteristics of VLPs . 10 nm particles can be used as a preliminary evaluation standard before the real virus morphology of PCV3 is discovered. Title: Self-assembly into virus\u2013like particles of the recombinant capsid protein of porcine circovirus type 3 and its application on antibodies detection", "Passage: VLPs, composed of viral structural proteins without genetic materials, are self-assembled macromolecules. Because of their ability in stimulating strong immune response and plentiful antibody production, they are regarded as candidates of novel vaccines. . VLPs provide more safety in use and the possibility of large scale production of vaccines with reproducible high quality results compared with traditional live-attenuated or inactivated virus vaccines . Some VLPs, such as Hepatitis B surface antigen VLPs, human papillomavirus VLPs and Malaria VLPbase vaccines have already been clinically used for the prevention of infectious diseases . In recent years, the technology of expressing capsid protein Title: Self-assembly into virus\u2013like particles of the recombinant capsid protein of porcine circovirus type 3 and its application on antibodies detection", "Passage: of PCV2 and self-assembly into virus-like particles has advanced, and can be used in multiple recombinant protein expression systems including baculovirus, yeast and E. coli . Many commercial vaccines based on VLPs have effectively prevented the infection of PCV2 . Similar to PCV2, there are two major open reading frames , ORF1 and ORF2, in PCV3 genome. ORF2 encode the immunogenic Cap which is the sole structural protein of the viral coat . Whether the idea of forming recombinant Cap into VLPs is equally applicable to PCV3 is the main purpose in our research. Title: Self-assembly into virus\u2013like particles of the recombinant capsid protein of porcine circovirus type 3 and its application on antibodies detection", "Passage: In conclusion, this is the first report of the ability of PCV3 VLPs to self-assemble which were successfully expressed in E. coli and applied in the development of an ELISA for testing the specific antibodies of clinical pig serum. The VLP ELISA was highly specific, sensitive and reproducible, it is a valuable tool to monitor the prevalence of the PCV3 virus. The invention of virus-like particles will play a significant role in providing a new tool for the study of PCV3.", "Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: To this end, we evaluated the antiviral effect of HCQ against SARS-CoV-2 infection in comparison to CQ in vitro. First, the cytotoxicity of HCQ and CQ in African green monkey kidney VeroE6 cells was measured by standard CCK8 assay, and the result showed \u00a9 The Author 2020 Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. . To better compare the antiviral activity of CQ versus HCQ, the dose-response curves of the two compounds against SARS-CoV-2 were determined at four different multiplicities of infection by quantification of viral RNA copy numbers in the cell supernatant at 48 h post infection . The data summarized in Fig. 1a and Supplementary Table S1 show that, at all MOIs , the 50% maximal effective concentration for CQ was lower than Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: different expression levels of virus nucleoprotein at the indicated drug concentrations at 48 h p.i. . Taken together, the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs. Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: controls for 1 h and then infected with SARS-CoV-2 at MOIs of 0.01, 0.02, 0.2, and 0.8. The virus yield in the cell supernatant was quantified by qRT-PCR at 48 h p.i. Y-axis represents the mean of percent inhibition normalized to the PBS group. The experiments were repeated twice. b, c Mechanism of CQ and HCQ in inhibiting virus entry. Vero E6 cells were treated with CQ or HCQ for 1 h, followed by virus binding at 4\u00b0C for 1 h. Then the unbound virions were removed, and the cells were further supplemented with fresh drug-containing medium at 37\u00b0C for", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: the surface-exposed N-terminal \u223c12 residues of the pVIII monomer lattice ; the N-terminal N1 and N2 domains of pIII ; and bacterial lipopolysaccharide embedded in the phage coat . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization . Primary antibody responses against the phage appear to be composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: the surface-exposed N-terminal \u223c12 residues of the pVIII monomer lattice ; the N-terminal N1 and N2 domains of pIII ; and bacterial lipopolysaccharide embedded in the phage coat . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization . Primary antibody responses against the phage appear to be composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination . The phage particle is immunogenic without adjuvant in all species tested to date, including mice , rats , rabbits , guinea pigs , fish , non-human primates , and humans . Various routes of immunization have been employed, including oral administration as well as subcutaneous , intraperitoneal , intramuscular , intravenous , and intradermal injection ; no published study has directly Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination . The phage particle is immunogenic without adjuvant in all species tested to date, including mice , rats , rabbits , guinea pigs , fish , non-human primates , and humans . Various routes of immunization have been employed, including oral administration as well as subcutaneous , intraperitoneal , intramuscular , intravenous , and intradermal injection ; no published study has directly", "Title: Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding\nPassage: the green oval. Title: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events\nPassage: EGFR signalling . The master regulator, the connecting proteins and regulated proteins are given as red, green and blue coloured inner node, respectively. Furthermore, each node is partitioned into four segments whereas the first segment seen from left refers to tumour specific proteins and is red-coloured. The second, third and fourth segments refer to either up-and down-regulated proteins, tumour specific gene expression changes and gene regulations in transgenic non-tumour liver tissue, respectively. Increased expression of either proteins or genes is given in red, whereas the blue colour denotes repressed expression. Title: Deciphering Biosignatures in Planetary Contexts", "Passage: The actual rule boundaries are shown by the light blue lines and the rules are listed at the top. Gray indicates regions lacking data . Dark green indicates that only histogram G had a nonzero value for that density/ neighbor count, while dark pink indicates only histogram R had a nonzero value. Light green indicates that histogram B had a higher frequency than histogram A at that density, and light pink indicates that histogram A had a higher frequency than histogram B at that density. It is readily apparent that boundaries between the histogram regions outlined above correspond very closely Title: A sensitive array-based assay for identifying multiple TMPRSS2:ERG fusion gene variants", "Passage: patterns of interstitial deletion between TMPRSS2 and ERG in a primary prostate tumor. An unpaired green dot suggests an interstitial deletion. Nonrandom variation of FISH patterns is shown by the fact that most of the green and red signals are paired in each panel. This variation is expected on a heterogeneous aneuploid cancer cell population, which often makes it difficult to distinguish meaningful events from random background aberrations.", "Title: Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral Restrictions at the Plasma Membrane\nPassage: The use of CCR5 appears to be essential for sexual transmission of HIV-1. Viruses that use CCR5 alone , or more rarely CCR5 and CXCR4 ], predominate in early infection . Individuals homozygous for a 32 base pair deletion in CCR5 that disrupts its expression are largely HIV-1 resistant . X4-using viruses tend to arise later in infection in some, but not all, individuals, and are associated with more rapid progression to AIDS. Whilst they can be transmitted by intravenous drug-use/transfusion, it is not clear why X4 viruses are almost never transmitted sexually given that target CD4+ T cells in Title: Long-Acting HIV-1 Fusion Inhibitory Peptides and their Mechanisms of Action", "Passage: be the promising candidate for treating and preventing HIV-1 infection. It is reported that in the early stage of HIV-1 infection, the co-receptor of HIV-1 is CCR5, which is then gradually converted into CCR5/CXCR4, and finally, further converted to CXCR4 . Because 47 strains of the virus in this study were mainly CCR5 strains, only 4 strains of CCR5/CXCR4, and no CXCR4 strain was detected, the effect of HIV-1 co-receptor utilization on the antiviral activity of HIV-1 fusion inhibitors could not be further analyzed. Title: Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies\nPassage: receptor and CCR5 co-receptor. The only exception was JRFL-CNE6_N97E_N279I_A281H, whose entry efficiency was reduced by approximately 42-fold relative to the original JRFL . Title: Selective use of primate CD4 receptors by HIV-1", "Passage: range of virus dilutions on Cf2Th cells stably expressing human CD4 and CCR5. For infection assays, Cf2Th cells stably expressing CD4 and CCR5 were plated at 3 x 10 4 cells/well of a 48-well plate 24 hours prior to infection. The cells were then infected with HIV-1 pseudoviruses at a multiplicity of infection of approximately 0.6 in the presence of 5 \u03bcg/ml of polybrene by spinoculation at 1,200 x g for 75 minutes. Fourty-eight hours post infection, the cells were harvested from the plate and fixed in 2% paraformaldehyde for 10 minutes. The fixed cells were washed three times with", "Title: Preparation of MS2 Phage-Like Particles and Their Use As Potential Process Control Viruses for Detection and Quantification of Enteric RNA Viruses in Different Matrices\nPassage: Reverse transcription was carried out using PrimeScript Reverse Transcriptase with slight modifications to the manufacturer's protocol. The RT mixture contained 0.5 nmol of dNTP mix , 20,000 molecules of IAC RNA, 2 pmol of both reverse primers , 4 \u00b5l of PrimeScript reaction buffer, 5 U of reverse transcriptase, 1 U of RNase inhibitor and 5 \u00b5l of isolated RNA. The reaction was performed at 50 \u2022 C for 1 h followed by 75 \u2022 C for 15 min and a cooling step at 10 \u2022 C. Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: Total RNA was extracted with Trizol from LCLs. Reverse transcription of 400ng total RNA was performed using AMV reverse transcriptase and random hexamers according to the manufacturer's protocol. SYBR green RT-qPCR analysis was run with the following cycling parameters: 10 min at 95 \u2022 C for initial polymerase activation followed by 40 cycles of 15 s at 95 \u2022 C and 1 min at 60 \u2022 C. The Taqman RT-qPCR experiments were performed using the thermal cycling protocol on the ABI StepOnePlus Real Time PCR System . All samples were run in duplicates and unless stated otherwise the human GAPDH Title: Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces", "Passage: An homogeneous quantity of the RNA samples was subjected to a reverse transcription step using the highcapacity cDNA archive kit as described by the manufacturer. Single-stranded cDNA products were then analyzed by real-time PCR using the TaqMan Gene Expression Assays according to the manufacturer's instructions . Single-stranded cDNA products were analyzed using the ABI PRISM 7700 Sequence Detector . The efficiency and reproducibility of the reverse transcription were tested using 18S rRNA TaqMan probes. Five assays were used, GAPDH-5 0 , GUSB-5 0 , GUSB-3 0 , TFRC-5 0 and TFRC-3 0 . In each case, duplicate threshold cycle values Title: Real-Time Reverse Transcription PCR Assay for Detection of Senecavirus A in Swine Vesicular Diagnostic Specimens", "Passage: strand synthesis was performed by addition of Sequenase enzyme ; followed by a ramped incubation to 37\u00b0C for 16 min followed by 2 min at 94\u00b0C. Subsequently, the 37\u00b0C incubation was repeated with the addition of Sequenase, and the final product was amplified using TaqR mastermix using manufacturers' recommended conditions. The resulting double stranded amplicon was processed for producing the sequencing library using a Nextera DNA sample preparation kit according to the manufacturers' protocol. Sequencing was performed with a 600-cycle MiSeq sequencing kit , and run on a MiSeq instrument.", "Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus\nPassage: in the mixed nucleolar fraction. Of note, nucleolin was equally distributed between the nuclear and cytoplasmic fractions. This distribution pattern for nucleolin appears to be specific for Jurkat T-cells as show previously . The nuclear protein PARP-1 was present in the nuclear and nucleoplasmic fraction but was depleted in the nucleolar fraction. Alpha-tubulin was highly abundant in the cytoplasmic fraction and weakly detected in the nuclear fractions. Collectively, these results confirmed that our methods produced a highly enriched nucleolar fraction without significant cross contamination. Title: Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells", "Passage: To investigate whether these bortezomib-induced changes in the tubulin polymerization were mediated by phosphorylation of stathmin, we examined the tubulin polymerization in stable U266 clones that overexpressing WT stathmin and the phosphorylation site-deficient stathmin mutants S16A, S25A and S38A. As shown in Figure 5C , by comparing with U266 cells, overexpression of WT stathmin and phosphorylation site-deficient mutants resulted in a significant decrease in the percent of polymerized tubulin following treatment with bortezomib . Title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice", "Passage: cells, with weaker intensity staining in Sgta +/\u2212 than WT, and no staining in Sgta \u2212/\u2212 animals, as expected . Conversely, AR protein was principally nuclear in WT and Sgta +/\u2212 prostate epithelial cells, with weaker intensity staining in Sgta +/\u2212 vs WT. However, in Sgta \u2212/\u2212 prostates, AR immunostaining was equally as intense as in the nuclei of WT prostate, but exhibited greater immunoreactivity in the cytoplasm than WT and Sgta +/\u2212 . In the testis, SGTA was also localised predominantly in the cytoplasm of cells and was detected in the Leydig, Sertoli, spermatid and spermatocyte cells of WT Title: GRASP depletion\u2013mediated Golgi destruction decreases cell adhesion and migration via the reduction of \u03b15\u03b21 integrin", "Passage: For determination of total protein synthesis, 40 \u00b5l of the cell lysate was precipitated with 10 \u00b5l of 100% TCA at 4\u00b0C for 10 min. The protein pellets were washed with acetone, dissolved in 0.2 M NaOH, neutralized with 0.2 M HCl, and mixed with Scintiverse BD cocktail . The incorporation of radioactivity was analyzed using scintillation counting and normalized based on the total protein amount.", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: The radiology department was divided into four areas : contaminated, semicontaminated, Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: , semicontaminated , buffer , and clean areas Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: the fever screening tents. The semicontaminated area includes the fever-CT control room, Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: . The contaminated area was separated from other areas by barriers.", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: The first three cases detected were reported in France on 24 January 2020 and had onset of symptoms on 17, 19 and 23 January respectively . The first death was reported on 15 February in France. As at 21 February, nine countries had reported cases : Belgium , Finland , France , Germany , Italy , Russia , Spain , Sweden and the UK . Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: in 31 countries, including 38 laboratories in 24 European Union and European Economic Area countries, had diagnostic capability for SARS-CoV-2 available , with cross-border shipment arrangements in place for many of those lacking domestic testing capacity. The remaining six EU/EEA countries were expected to have diagnostic testing available by mid-February . Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Text: A respiratory viral disease caused by the Middle East Respiratory Syndrome CoronaVirus was first isolated in 2012, in a 60-year-old man who died in Jeddah, KSA due to severe acute pneumonia and multiple organ failure . Since then, 27 countries have reported the presence of this virus, including the 12 countries of the Eastern Mediterranean region. Several outbreaks have occurred in multiple countries including Saudi Arabia, the United Arab Emirates and the Republic of Korea . Recent fatality rate of 21% . Very limited evidence is available for exploring the epidemiology of this virus among the pediatric population . Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections", "Passage: Middle East respiratory syndrome was first reported in September 2012 in Saudi Arabia, following isolation of MERS-CoV from a male patient who died months earlier from severe pneumonia and multiple organ failure . In the 8 years since then, there have been more than 2494 confirmed cases of MERS resulting in upwards of 858 deaths globally . While 27 countries have reported cases of MERS, approximately 80% of confirmed cases originated in Saudi Arabia . To date, all known cases of MERS can be linked to travel or residence in countries along the Arabian Peninsula-that is, Bahrain; Iraq; Iran; Israel,", "Title: Estimating the number of infections and the impact of non-\nPassage: Department of Mathematics, Imperial College London Title: Estimating the number of infections and the impact of non-\nPassage: Imperial College COVID-19 Response Team Title: Estimating the number of infections and the impact of non-\nPassage: Imperial College COVID-19 Response Team Title: Estimating the number of infections and the impact of non-\nPassage: Imperial College COVID-19 Response Team", "Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management\nPassage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\". Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: families and healthcare settings . Clinical pictures of this infection varied from asymptomatic to mild respiratory symptoms to severe respiratory distress and death . Severe ailment can often cause respiratory catastrophes that need mechanical ventilation and support in ICUs across different healthcare settings . Studies have suggested an incubation period of 16 days with a mean of 5-6 days , while the median time until death is 11-13 days among severely ill patients . e gold standard test for the detection of this virus is real-time reverse-transcription polymerase chain reaction assays .", "Title: Estimating the number of infections and the impact of non-\nPassage: main analysis. Title: Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine\nPassage: in the same shading. Title: Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine\nPassage: training subsets , and assessing the resulting difference in the performance of the classifier. Title: Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses\nPassage: the last neutralization step, to transfer the basic solution to the eluent.", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: same contact sites as the human ACE2 gene for interacting with SARS CoV , it was proposed that an intermediate host may not be necessary and that some bat SL-CoVs may be able to directly infect human hosts. To directly address this possibility, the exact S gene from bat coronavirus SL-SHC014 was synthesized and used to generate a chimeric virus in the mouse adapted MA15 SARS-CoV backbone. The resultant SL-SHC014-MA15 virus could indeed efficiently use human ACE2 and replicate in primary human airway cells to similar titres as epidemic strains of SARS-CoV. While SL-SHC014-MA15 can replicate efficiently in young and Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: The findings may help to explain why bats are often the source for viruses that are deadly in humans. Learning more about bats' antiviral defenses and how they drive virus evolution may help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. More studies are needed in bats to help these efforts. In the meantime, the experiments highlight the importance of warning people to avoid direct contact with wild bats. up resource supply of infection-susceptible host cells, were first developed for HIV but have since been applied to other chronic infections, including Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: causing pathology to their hosts. Such rapidly-reproducing viruses would likely generate extreme virulence upon spillover to hosts lacking similar immune capacities to bats. Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence", "Passage: countered by the virus spreading more quickly from cell to cell. This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures like humans are not.", "Title: Viral factors in influenza pandemic risk assessment\nPassage: could inspire hypothesis-driven experiments . Title: Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel\nPassage: further explore the associations identified in this hypothesisgenerating study. Title: Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel", "Passage: Our hypothesis-generating study found a statistically significant positive HR between HHV-6 and schizophrenia among men and between HSV-1 and schizophrenia among blacks discharged or retired from the military with a diagnosis of schizophrenia and a history of mental health hospitalization. A negative association with HSV-2 and CMV was noted among women and blacks. Blacks dominated the results for women. These findings should be interpreted with caution, however, because they are driven by a small number of subjects and may be the result of type I error. Further analysis is warranted with a larger sample size. No significant associations were observed Title: Mapping the drivers of within-host pathogen evolution using massive data sets", "Passage: I would also like to know what proportion of substitutions inferred by the HMM are likely, under the model, to be explained by selection linked to the measured phenotypes. This might be a useful statistic to output to get an impression of what is going on. Other indication of measured effect sizes would also/alternatively be welcome.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: it has been extremely difficult to elicit antibody responses that cross-react with native protein epitopes using peptides. The overall picture is considerably bleaker than that painted by Table 2 , since in several studies either: peptide ligands selected from phage-displayed libraries were classified by the authors as mimics of discontinuous epitopes if they bore no obvious sequence homology to the native protein, which is weak evidence of non-linearity, or the evidence for cross-reactivity of antibodies elicited by immunization with phage-displayed peptides with native protein was uncompelling. Irving et al. describe at least one reason for this lack of success: it Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: it has been extremely difficult to elicit antibody responses that cross-react with native protein epitopes using peptides. The overall picture is considerably bleaker than that painted by Table 2 , since in several studies either: peptide ligands selected from phage-displayed libraries were classified by the authors as mimics of discontinuous epitopes if they bore no obvious sequence homology to the native protein, which is weak evidence of non-linearity, or the evidence for cross-reactivity of antibodies elicited by immunization with phage-displayed peptides with native protein was uncompelling. Irving et al. describe at least one reason for this lack of success: it Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For the most part, peptides displayed on phage elicit antibodies in experimental animals , although this depends on characteristics of the peptide and the method of its display: pIII fusions tend toward lower immunogenicity than pVIII fusions possibly due to copy number differences . In fact, the phage is at least as immunogenic as traditional carrier proteins such as bovine serum albumin and keyhole limpet hemocyanin , and has comparatively few endogenous B-cell epitopes to divert the antibody response from its intended target . Excepting small epitopes that can be accurately represented by a contiguous short amino acid sequence, however, Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For the most part, peptides displayed on phage elicit antibodies in experimental animals , although this depends on characteristics of the peptide and the method of its display: pIII fusions tend toward lower immunogenicity than pVIII fusions possibly due to copy number differences . In fact, the phage is at least as immunogenic as traditional carrier proteins such as bovine serum albumin and keyhole limpet hemocyanin , and has comparatively few endogenous B-cell epitopes to divert the antibody response from its intended target . Excepting small epitopes that can be accurately represented by a contiguous short amino acid sequence, however,", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS-CoV was found and characterized because of its apparent association with severe, and therefore more obvious, illness in humans; we were the canaries in the coal mine. Sero-assays and prospective cohort studies have yet to determine the extent to which milder or asymptomatic cases contribute to MERS-CoV transmission chains. However, transmission of MERS-CoV is defined as sporadic , intra-familial, often healthcare associated, inefficient and requiring close and prolonged contact In a household study, 14 of 280 contacts of 26 MERS-CoV positive index patients were RNA or antibody positive; the rate of general transmission, even in outbreaks is around 3 % Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: of \"contact\" during these interviews has been defined for one study . Despite this lack of clarity, the WHO consider that evidence linking MERS-CoV transmission between DCs to humans is irrefutable . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first WHO case definition defined probable cases of MERS based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract involvement. It also included roles for contact with a probable or confirmed case or for travel or residence within the Arabian Peninsula. If strictly adhered to, only the severe syndrome would be subject to laboratory testing, which was the paradigm early on . From July 2013, the revised WHO case definition included the importance of seeking out and understanding the role of asymptomatic cases and from June 2014, the WHO definition more Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: It became apparent early on that MERS-CoV spread relatively ineffectively from human-to-human. Despite ongoing and possibly seasonal introduction of virus to the human population via infected DCs and perhaps other animals yet to be identified, the vast majority of MERS-CoV transmission has occurred from infected to uninfected humans in close and prolonged contact through circumstances created by poor infection control in health care settings. This opportunistic virus has had its greatest impact on those with underlying diseases and such vulnerable people, sometimes suffering multiple comorbidities, have been most often associated with hospitals, creating a perfect storm of exposure, transmission and", "Title: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study\nPassage: were more pronounced. Moreover, the results of the seasonal score were very similar or even stronger than those of the three-years score, arguing for the adequacy to query six months infectious events in future studies to identify the infection-prone sub-group of the population. Lifestyle habits seem to contribute to an individual's risk for RTI. Among them, cigarette smoking has been reported as a major environmental risk factor for recurrent and severe RTIs . Frequent contact to small children , vitamin D deficiency , and lack of physical activity constitute other exposures associated with heightened RTI risks. Moreover, higher levels of Title: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study", "Passage: were more pronounced. Moreover, the results of the seasonal score were very similar or even stronger than those of the three-years score, arguing for the adequacy to query six months infectious events in future studies to identify the infection-prone sub-group of the population. Lifestyle habits seem to contribute to an individual's risk for RTI. Among them, cigarette smoking has been reported as a major environmental risk factor for recurrent and severe RTIs . Frequent contact to small children , vitamin D deficiency , and lack of physical activity constitute other exposures associated with heightened RTI risks. Moreover, higher levels of Title: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study", "Passage: For a better understanding of the robustness of the relationship between RTI burden and obesity, the effect of adjusting for putative confounders was explored . The studied demographic and lifestyle variables did only marginally affect ORs. However, adjustment for asthma, chronic obstructive pulmonary disease or a summary score covering all queried co-morbidities weakened the relationship between obesity and all outcomes considerably. Adjustment for vitamin D levels among those for which serum was available , had only a slight effect on the magnitude of the association between obesity and RTI outcomes. Title: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study", "Passage: For a better understanding of the robustness of the relationship between RTI burden and obesity, the effect of adjusting for putative confounders was explored . The studied demographic and lifestyle variables did only marginally affect ORs. However, adjustment for asthma, chronic obstructive pulmonary disease or a summary score covering all queried co-morbidities weakened the relationship between obesity and all outcomes considerably. Adjustment for vitamin D levels among those for which serum was available , had only a slight effect on the magnitude of the association between obesity and RTI outcomes.", "Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess\nPassage: total of 3711 persons , 199 symptomatic cases have been diagnosed on board as of 24 February, and additional asymptomatic infections and symptomatic cases after disembarkation have also been reported. Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: Text: An outbreak of novel coronavirus disease has occurred on a cruise ship, the Diamond Princess . The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 Title: Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess", "Passage: February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 and 766 cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards.", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: virus is usually described by the media as 'deadly' and although this is true in the sense that it has caused deaths, the nuances of uncertain case fatality rates in the early stages of an outbreak are not being communicated. The current estimated case fatality rate seems to be around 3% which is significant but not comparable to the 10% rate for SARS or 34% reported for MERS. These misperceptions are still driving public anxiety. Title: Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections\nPassage: 8422 probable cases, leading to 916 deaths in 29 countries, with the majority of cases occurring in mainland China and Hong Kong. Approximately 30% of infections occurred in healthcare workers. By the termination of the epidemic the global CFR was 11% . Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: SARS-CoV and MERS-CoV cause severe disease, but despite the initial R0 estimations of greater than 2.0 for SARS-CoV , and some large outbreaks, neither were as transmissible as initial concerns suggested. SARS-CoV caused 8098 reported cases and 774 deaths in 37 countries before the epidemic was controlled. Control was thought to have been possible because a high proportion of cases were severe, making it easier to rapidly identify and isolate infected individuals. In addition, the virus was present at lower levels in upper airway secretions. There was no secondary transmission in the United States from the 8 imported cases, although Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Is 2019-nCoV infection severe? To date approximately 14% of cases of 2019-nCoV have been described as severe by WHO, with a case-fatality rate of 2.1%.10 Estimates of severity are usually higher in the beginning of an epidemic due to the identification of the most severely affected cases and decline as the epidemic progresses. However, because many infected persons have not yet recovered and may still die, the case-fatality rate and severity could be underestimated. On January 30, 2020, WHO officially declared the 2019-nCoV epidemic as a Public Health Emergency of International Concern, indicating its concern that countries aside from China", "Title: Stearoyl-CoA desaturase inhibition blocks formation of hepatitis C virus-induced specialized membranes\nPassage: and pharmacological inhibition of SCD-1 leads to an antiviral effect similar to DAAs. Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: The advent of DAAs therapies constitutes one of the major breakthroughs in HCV infected patients management. However, these new treatment options are far from being universally available, in particular for HCV infected patients relying on Latin American public healthcare systems. The main limiting factors for worldwide access to DAAs in our region concern the high cost, the inadequate management of public healthcare systems, the limited access of low-income or uninsured populations to healthcare providers, and the lack of accurate epidemiological information . In Uruguay, these therapies became recently available, and although some have been approved for their use by the Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: The advent of DAAs therapies constitutes one of the major breakthroughs in HCV infected patients management. However, these new treatment options are far from being universally available, in particular for HCV infected patients relying on Latin American public healthcare systems. The main limiting factors for worldwide access to DAAs in our region concern the high cost, the inadequate management of public healthcare systems, the limited access of low-income or uninsured populations to healthcare providers, and the lack of accurate epidemiological information . In Uruguay, these therapies became recently available, and although some have been approved for their use by the Title: Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients", "Passage: Each drug or class of DAA is characterized by specific resistance profiles. The likelihood that a DAA will select for and allow outgrowth of viral populations carrying RASs depends on the DAA's genetic barrier to resistance , the viral fitness of the resistant variant, and viral genotypes and subtypes .", "Title: CDC Summary 21 MAR 2020,\nPassage: The complete clinical picture with regard to COVID-19 is not fully known. Reported illnesses have ranged from very mild to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, a reportexternal icon out of China suggests serious illness occurs in 16% of cases. Older people and people of all ages with severe chronic medical conditions \u2014 like heart disease, lung disease and diabetes, for example \u2014 seem to be at higher risk of developing serious COVID-19 illness. A CDC Morbidity & Mortality Weekly Report that looked at severity of disease among COVID-19 Title: CDC Summary 21 MAR 2020,\nPassage: Older people and people with severe chronic conditions should take special precautions because they are at higher risk of developing serious COVID-19 illness. Title: The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts", "Passage: Epidemiologic studies have shown that severe immunosuppression is a major comorbidity that places individuals at the highest risk of severe morbidity and mortality due to influenza infection. Patients with AIDS have increased duration of disease due to influenza and higher incidence of pneumonia leading to increased mortality . A study of hospitalized patients with leukemia and influenza reported 80% with pneumonia and 33% mortality . More recently during the 2009 pandemic, studies reported similarly high levels of lower respiratory tract disease and need for hospitalization in those with hematologic malignancies and solid tumors undergoing chemotherapy . Title: Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses", "Passage: Infection. The 1918 H1N1 as well as the recent 2009 pandemics were both notable for the comparatively high rates of morbidity among healthy, young adults not typically observed with seasonal influenza . During the recent pandemic, several studies of confirmed pH1N1 cases in Canada and the US reported the median age of severe infections to be 23-27 years old . In Canada, 30%-48% of infections also presented in persons with comorbidities; diabetes, heart disease, and immunosuppression were associated with the highest risk of severe infection, while lung diseases and obesity were among the most common underlying conditions . The role", "Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China\nPassage: The SIR model for an infectious disease can be written as follows : Title: Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China\nPassage: In this study, we use the known SIR model for the dynamics of an epidemic . For the parameter identification, we will use the exact solution of the SIR set of linear equations and statistical approach developed in ). These methods were applied for investigation of the children disease, which occurred in Chernivtsi in 1988-1989. We will estimate some of the epidemic characteristics and present the dependencies for victim numbers, infected and removed persons versus time. Title: A Simulation Optimization Approach to Epidemic Forecasting", "Passage: Ohkusa et al. also used a simple SIR model for forecast during the pandemic. In contrast, Ong et al. described a real-time system to both monitor and forecast different epidemic outcome measures in Singapore during the 2009 pandemic. The surveillance system collected data on ILI instances from twenty three participating general practice and family doctor clinics in Singapore. Since H1N1 had low hospitalization and mortality rates, the study did not use hospital and fatality data. A stochastic compartmental model with particle filtering was used in real-time epidemic incidence forecast. ILI data collected at general practice and family doctor clinics in Title: Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases", "Passage: The modelling and prediction approaches developed here for a comparison to other methods) provide tools for real time estimation of epidemiological parameters that are appropriate for emerging infectious diseases. The method is intentionally simple, relying on standard epidemiological population models, in order to be commensurate with the paucity of epidemiological data typically available for emerging infectious diseases. These features are illustrated by the application of the method to H5N1 influenza infection time series in humans. Clearly, the SIR class of models, even when cast in probabilistic terms, relies on several general assumptions, which are simplistic in specific situations. First, these", "Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response\nPassage: Almost one half of the disease burden in low-and middle-income countries is now from noncommunicable diseases. Ischaemic heart disease and stroke are the largest sources of this burden, especially in the low-and middle-income countries of Europe, where cardiovascular diseases account for more than one quarter of the total disease burden. Injuries accounted for 17% of the disease burden in adults aged 15-59 years in 2004. In the low-and middleincome countries of the Americas, Europe and the Eastern Mediterranean Region, more than 30% of the entire disease and injury burden among men aged 15-44 years was from injuries. Title: The social benefits of private infectious disease-risk mitigation", "Passage: Observed data on the DALY losses to disease indicate that developed countries account for only 12 % of worldwide losses due to death and disability, but for more than 90 % of health expenditure. Infectious diseases of the type modeled here are overwhelmingly a problem of the developing world, accounting for more than 34 % of DALYs in developing countries, but less than 5 % in developed countries . Our findings suggest that one explanation for this lies in differences in the private response to disease risk in developed and developing countries and hence to differences in the relative private Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: The high levels of burden of disease for the WHO African, South-East Asia and Eastern Mediterranean regions compared to other regions are predominantly due to Group I conditions , although injury DALY rates are also higher than in other regions . European low-and middle-income countries have a substantially higher noncommunicable disease burden than high-income countries . They also have a higher burden due to Group I causes and Group III causes . In fact, these countries have the highest proportion of burden due to injuries of all the regions, followed by the low-and middleincome countries of the Americas. Title: Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response", "Passage: In Africa, HIV/AIDS, lower respiratory infections and diarrhoeal disease are the leading causes of burden of disease, whereas in the Eastern Mediterranean and in South-East Asia, lower respiratory infections and diarrhoeal disease are the two leading causes. In all three of these regions, problems during pregnancy and childbirth are important and preventable causes of burden of disease. The role of road traffic accidents in these regions, and of war and conflict in the Eastern Mediterranean, should also be noted.", "Title: RNAi Therapeutic Platforms for Lung Diseases\nPassage: The second is the airway cell membrance and its intracellular barriers . For efficient gene silencing in the lungs, siRNAs must be delivered to their site of action, be stable, enter the target cells, and be present in the cytoplasm at sufficient concentration. Once the siRNAs reach the target cells, they must be trafficked into the cytoplasm and taken up by Argonaute 2/RNA-induced silencing complex , which degrades mRNAs and, subsequently, suppresses the sequence-specific gene expression. For efficient endocytosis to occur, particles should be under 150 nm in size. Particles within this size range could also avoid macrophage uptake and Title: Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation", "Passage: 2% FBS/0.2 mM EDTA/PBS , filtered through a 40 mm strainer, and counted in a Vi-CELL cell viability analyzer. Title: Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation\nPassage: 2% FBS/0.2 mM EDTA/PBS , filtered through a 40 mm strainer, and counted in a Vi-CELL cell viability analyzer. Title: Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation\nPassage: Animals were dosed with si-Ctnnb1 siRNA labeled with DyLight650 fluorophore and sacrificed 2 or 72 h post-dosing. Tracheas were cannulated with a 20G teflon angiocath catheter to inflate the lungs with 1 mL of 10% neutral-buffered formalin solution and tied with surgical suture. Lungs were excised and immersed in additional 10% neutral-buffered formalin solution for 24 h, paraffin-processed, and sectioned at 5 mm.", "Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: The time series data of 2019-nCoV cases in mainland China were initially released by the Wuhan Municipal Health Commission from 10 to 20 January 2020 , and later by the National Health Commission of China after 21 January 2020 . The case time series data in December 2019 were obtained from a published study . All cases were laboratory confirmed following the case definition by the national health commission of China . We chose the data up to 24 January 2020 instead of to the present study completion date. Given the lag between timings of case confirmation and news release Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: For the simulated daily number of cases , see Figure 1d , we found that \u03b5 i matched the observed daily number after 17 January 2020, but was significantly larger than the observations from 1 to 17 January 2020. This finding implied that under-reporting was likely to have occurred in the first half of January 2020. We estimated that the reporting rate after 17 January 2020 increased 21-fold compared to the situation from 1 to 17 January 2020 on average. One of the possible reasons was that the official diagnostic protocol was released by WHO on 17 January 2020 , Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "Passage: . Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation. Title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak\nPassage: and the diagnosis and reporting efforts of 2019-nCoV infections probably increased. Thereafter, the daily number of newly reported cases started increasing rapidly after 17 January 2020, see Figure 1d . We conducted additional sensitivity analysis by varying the starting date of the under-reporting time window, e.g., 1 January 2020 in the main results, from 2 December 2019 to 3 January 2020, and we report our estimates largely hold. The exact value of the reporting rate was difficult to determine due to lack of serological surveillance data. The reporting rate can be determined if serological surveillance data are available for a", "Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys\nPassage: In 2005 the World Health Organization recommended its member states to revise or construct a preparedness plan for pandemic influenza. The WHO also set up a system of influenza pandemic alert levels. Phases 1-3 include capacity development and response planning, while phases 4-6 signify the need for response and mitigation efforts. 1 By August 2008, 47 countries had prepared such a plan. 2 The recent spread of infection with a novel influenza A virus of swine origin has prompted governments to review and carry out their pandemic responses, including vaccination strategies. Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys", "Passage: The second survey was conducted in May 2009 when the WHO pandemic influenza alert level assigned to H1N1 influenza was phase 5. Phase 5 signifies human to human spread of the virus into at least two countries within one WHO region. Although most countries are not affected at this stage, the declaration of phase 5 is a strong signal that a pandemic is imminent and that the time to finalise the organisation, communication, and implementation of the planned mitigation measures is short. 1 During this phase 5 period, we repeated our questionnaires in the three specialties in one hospital. All Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys\nPassage: virus has gained the level of transmissibility among humans necessary to cause a pandemic. Title: Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys", "Passage: The first survey was conducted from January 2009 to March 2009. The WHO influenza pandemic alert level assigned to H5N1 during that period was phase 3. Phase 3 signifies an animal or human-animal influenza reassortant virus that has caused sporadic cases or small clusters of disease in people but has not resulted in human to human transmission sufficient to sustain community level outbreaks. Limited human to human transmission may occur under some circumstances, such as when there is close contact between an infected person and an unprotected carer. However, limited transmission under such restricted circumstances does not indicate that the", "Title: Macroevolutionary Immunology: A Role for Immunity in the Diversification of Animal life\nPassage: are also an essential part of such studies. Title: On pandemics and the duty to care: whose duty? who cares?\nPassage: the case that both these factors played a significant role in the observed retrenchment over time. Title: Can \"presumed consent\" justify the duty to treat infectious diseases? An analysis", "Passage: It is quite easy to imagine more than one answer to this question, but one thing is for sure: any thoughtful answer would acknowledge that choice is determined both by factors that are under the control of the individual and by factors that are not. Personal factors such as educational status, perception of the world and ambitions all influence an individual's choice of profession strongly. Nevertheless, factors outside the individual's control also play a large role in determining that choice. The environment in which the person grew up -their family life, the jobs of their parents, their community, social class Title: Role of Oct4 in the early embryo development", "Passage: Recent studies have found that certain maternal factors are involved in the regulation of Oct4 expression, providing clues on the mechanism underlying the initiation of totipotency/pluripotency. Cancer-associated factor Tpt1 has been reported to activate the transcription of Oct4 and Nanog in transplanted somatic nuclei in the Xenopus oocyte , but another study failed to replicate this finding upon knockdown of Tpt1 by Small interfering RNA in the mouse embryos . Components of the ATP-dependent BAF chromatinremodeling complex have been shown to significantly increase reprogramming efficiency when used together with the Yamanaka's 4 factors . Promyelocytic leukemia protein was found to", "Title: Techniques to Study Antigen-Specific B Cell Responses\nPassage: and more efficacious vaccine candidates . Influenza also performs fusion through the stem region of the hemagglutinin protein, and the identification of B cells that target this relatively conserved site has spurred research on the development of a universal influenza vaccine . Like RSV, HIV, and influenza, the fusion proteins of EBV and CMV exist in a pre-fusion conformation, and stabilization in their pre-fusion states could greatly accelerate vaccine development against these pathogens . Rare memory B cells producing antibodies specific for the EBV fusion machinery have been isolated; these can neutralize both B cell and epithelial cell infection . Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: and more efficacious vaccine candidates . Influenza also performs fusion through the stem region of the hemagglutinin protein, and the identification of B cells that target this relatively conserved site has spurred research on the development of a universal influenza vaccine . Like RSV, HIV, and influenza, the fusion proteins of EBV and CMV exist in a pre-fusion conformation, and stabilization in their pre-fusion states could greatly accelerate vaccine development against these pathogens . Rare memory B cells producing antibodies specific for the EBV fusion machinery have been isolated; these can neutralize both B cell and epithelial cell infection . Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: There are no ideal animal models to provide needed information on influenza immunity sufficient to bring a universal vaccine to licensure. Human challenge studies are, and will continue to be, of paramount importance. Expanding challenge study capacity is a key priority. Viral challenge studies are required not only to understand natural history and pathogenesis, but also to characterize the protective immune responses in the various immune compartments, to conduct proof-of-principle passive immunotherapy studies, and to evaluate safety and efficacy of candidate vaccines themselves. It is noteworthy that to evaluate the \"universality\" of a putative universal vaccine, we must challenge humans Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: Nevertheless, a rapidly growing knowledge base suggests new approaches to developing better influenza vaccines that can provide broader and more durable immunity than that offered by current vaccines. Fruitful lines of research include identifying critical epitopes shared by different influenza viruses and using these as immunogens; optimizing NA immunity; and eliciting robust local immunity within the MALT, iBALT, and lung immune compartments. The best future influenza vaccines will ideally elicit robust and persistent protective immune responses to multiple epitopes on multiple influenza proteins expressed in multiple anatomical compartments, and immune responses capable of being productively recalled upon wild virus exposure.", "Title: A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients\u2019 responses to H7N9 infection\nPassage: the inferior turbinate and paranasal sinus-derived cultures as \"upper anatomical location\" ) and larynx-and bronchus-derived cultures as \"lower anatomical location\" ) for statistical evaluation. Spearman's rank correlation coefficients revealed that a lower anatomical location was significantly inversely associated with male sex . Age \u2265 65 years, medical comorbidity, and obesity were not significantly associated with the other patient characteristics . The epithelial origin of cultured cells was confirmed by immunofluorescence staining using an anti-cytokeratin 19 antibody. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: the lower airway environment, resulting in prolong exacerbation episodes following viral infection. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the lower airway is the site of dysregulated inflammation in most chronic airway inflammatory diseases, the upper airway remains the first point of contact with sources of exacerbation. Therefore, their interaction with the exacerbation agents may directly contribute to the subsequent responses in the lower airway, in line with the \"United Airway\" hypothesis. To elucidate the host airway interaction with viruses leading to exacerbations, we thus focus our review on recent findings of viral interaction with the upper airway. We compiled how viral induced changes to the upper airway may contribute to chronic airway inflammatory disease exacerbations, to provide Title: Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections", "Passage: The region where the airway meets the alveolus has been termed the bronchoalveolar duct junction . The distal airway epithelium contains Clara cells defined by their cuboidal appearance and expression of secretoglobin family 1A, member 1 , also called Clara Cell Secretory Protein or uteroglobin. During recovery from naphthalene depletion, a population of Club cells proliferates from neuroendocrine bodies and from the BADJ . These bronchoalveolar stem cells express airway Scgb1a1, alveolar Type II surfactant protein -C, the stem cell markers Sca-1, and CD34, but not CD45 . These BASCs are able to self-renew and maintain expression of both airway", "Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies\nPassage: the site of inoculation, followed by dissemination stage and, later, persistent infection . However, an individual patient can show highly variable disease progression with different patterns of organ involvement and disease severity. Erythema migrans is often seen at the site of the tick bite after 3-30 days of incubation. Regional lymphadenopathy can be seen. Secondary skin lesions represent hematogenous dissemination. At this stage, constitutional symptoms of general fatigue, fever and headaches, migratory musculoskeletal pain, conjunctivitis, and cardiac involvement occur. In total, 15% of untreated patients can develop frank neurologic manifestations of meningitis, encephalitis, and variable forms of neuritis with fluctuating Title: A Note on the Risk of Infections Invading Unaffected Regions", "Passage: and Germany , the three countries which received the highest numbers of immigrants from undervaccinated areas . Title: A Note on the Risk of Infections Invading Unaffected Regions\nPassage: Many countries where infectious diseases had been considered controlled in past decades are reporting the invasion of some exotic and frequently unknown infectious diseases that are spread by infected travellers/immigrants . Historical examples of disease invasion are numerous. A particular tragic invasion was the invasion of Europe by the Black Death in XIV century, which started probably in China and travelled by ship until reaching European shores where it decimated from a quarter to a half of the European population . Another tragic invasion occurred in the beginning of the last century when between 50 and 100 million individuals worldwide Title: Spatial dynamics of the 1918 influenza pandemic in England, Wales and the United States", "Passage: The analysis requires an estimate of when each city became infected to allow potential sources of that infection to be identified. For each city infected in week t, the candidate infectors are those infected in any week before t. We define the infection week of city i, t i , to be the first that meets a set of conditions on mortality in weeks t i \u00fe 1, t i \u00fe 2 and t i \u00fe 3. We use mortality values ahead of t i to include the time from infection to death. A week could be designated the infection", "Title: Modeling the impact of quarantine during an outbreak of Ebola virus disease\nPassage: To show that all solutions of the model The result below follows from the above analyses. Title: Testing Modeling Assumptions in the West Africa Ebola Outbreak\nPassage: model. However, we believe that newer data will confirm our initial conclusions. Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: the fact that in all waves and places the BRT model found the spatial autocorrelation term to have the highest rank of influence. As expected, the relative influence of the autocorrelation term at the national level was higher than at the delta levels . In the GLMM models we found the Akaike Information Criterion using the entire set of 14 variables to be much lower than the AICs of a GLMM model without fixed effects. This indicated that though clustering effects were significant, our theory driven predictor variables improved model performance.", "Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Up to present, the main infection source was the patients who with pneumonia infected by the 2019-nCoV. Respiratory droplet transmission is the main route of transmission, and it can also be transmitted through contact . Although many details, such as the source of the virus and its ability to spread between people remain unknown, an increasing number of cases show the signs of human-tohuman transmission . Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: It is currently unclear how 2019-nCoV is spread, but it is suspected to be transmitted through contact with infected respiratory secretions, like other known coronaviruses. There are instances of sustained human-to-human transmission across generations of cases, especially near the epicenter in Wuhan City. 21 Current evidence suggests that close contact with an infected person is a major factor in disease transmission. CDC defines \"close contact\" 33 as being in or within two meters of an area with a confirmed patient or being directly exposed to infectious secretions without appropriate PPE. Healthcare facilities in China have reported spread from person to Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: could be affected by 2019-nCoV. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: 9.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: However, individual SI algorithms may stock at local optima. Therefore, one solution is to apply hybrid SI algorithms to avoid this problem. In , a hybrid of two SI algorithms, namely GA and SSA, was presented to improve the ANFIS model. The proposed new model called GA-SSA-ANFIS was applied to forecast crude oil prices for long-term time series data. However, the previously mentioned methods suffer from some limitations that can affect the performance of the forecasting output such as slow convergence and the ability to balance between exploration and exploitation phases can influence the quality of the final output. This Title: On computational approaches for size-and-shape distributions from sedimentation velocity analytical ultracentrifugation", "Passage: We will refer to this approach as the ''standard algorithm,'' because it is firmly rooted in textbook linear algebra and basic linear least-squares optimization, and utilized in many applications throughout the biophysical literature and physical sciences. We have introduced this approach previously into the SV analysis, and it underlies all size-distribution analyses in SEDFIT and SEDPHAT. If used without regularization, it provides exact solutions to the least-squares problem , and when used with regularization, the algorithms ensure that fits with statistically indistinguishable quality are obtained. Title: On computational approaches for size-and-shape distributions from sedimentation velocity analytical ultracentrifugation", "Passage: Further, all computations can be condensed to the normal Eq. , requiring essentially only a matrix P of 1,000 9 1,000 numbers to be operated on, which even as double-precision data type requires less than 8 MB, trivial by current standards on any platform. Once condensed to the form of Eq. , our SV problem is far smaller than common problems of analogous mathematical structure, for example, in astronomical image analysis . For the data shown in Fig. 1 , in the implementation in SEDFIT , *20 MB of RAM are used. Title: A mechanistic spatio-temporal framework for modelling individual-to-individual transmission\u2014With an application to the 2014-2015 West Africa Ebola outbreak", "Passage: We also fit the full individual-based SEIR model to one of the simulated datasets described in Simulating from Individual SEIR Model. It is noted that this will require an explicit consideration of each individual in the model fitting and often require a large amount of recalculations of likelihood during the MCMC sampling \u2212 for example, at proposing a new value of \u03ba , the spatial infectivity between all infectious-susceptible pairs must be recalculated. As the purpose here is to compare the computational efficiency, we only record and compare the run-time for 1000 MCMC iterations both in performing the full individual-based", "Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: This makes it necessary to deepen our knowledge of the effect of aging and its interaction with the most prevalent chronic diseases in the elderly and the immune response in order to implement preventive measures to provide better protection of this population group . Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: 0.003] . Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: The author mentioned that this study has an advantage over the diary based data. It is worth to see the discrepancy of between two approaches in this study. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: A lay summary of the results will be shared with the participating schools and households, as well as and communities surrounding the schools. Manuscripts will be submitted to appropriate journals discussing the methods, statistical analysis and output, and applications of the data in mathematical modelling of respiratory disease transmission and control.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The detection of MERS-CoV antigen has not been common to date but the combination of short turnaround time from test to result, high throughput and identification of viral proteins makes this an attractive option. Detection of viral proteins rather than viral RNA indicates the likely presence of infectious virus. The first rapid immunochromatographic tool described could detect recombinant MERS-CoV nucleocapsid protein from DC nasal swabs with 94 % sensitivity and 100 % specificity compared to RT-rtPCR . A different approach used a monoclonal antibody-based capture ELISA targeting the MERS-CoV nucleocapsid protein with a sensitivity of 10 3 TCID 50 and Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: In-house anti-SARSr-CoV IgG and IgM ELISA kits were developed using SARSr-CoV Rp3 NP as antigen, which shared above 90% amino acid identity to all SARSr-CoVs, as reported previously . For IgG test, MaxiSorp Nunc-immuno 96 well ELISA plates were coated overnight with recombinant NP. Human sera were used at 1:20 dilution for 1 h at 37\u00b0C. An anti-Human IgG-HRP conjugated monoclonal antibody was used at a dilution of 1:40,000. The OD value was calculated. For IgM test, Maxi-Sorp Nunc-immuno 96 wellELISA plates were coated overnight with anti-human IgM . Human sera were used at 1:100 dilution for 40 min at Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Some sero-assays have bypassed the risks of working with infectious virus by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins , or using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase . A pseudo particle neutralization assay has seen widespread used in animal studies and was at least as sensitive as the traditional microneutralization test. ] Studies using small sample numbers and ppNT found no evidence of MERS-CoV neutralizing antibody in sera from 158 children with LRT infections between May 2010 and May 2011, 110 sera from 19 to 52 year old male blood Title: Development of a Rapid Diagnostic Test Kit to Detect IgG/IgM Antibody against Zika Virus Using Monoclonal Antibodies to the Envelope and Non-structural Protein 1 of the Virus", "Passage: Monoclonal antibodies showing high affinity constant to recombinant proteins were selected among the various hybridoma types. IgG1 from hybridoma J5E1 showed a 1.5 to 10 fold strong affinity to recombinant E antigen compared to isotypes from other hybridomas . On the other hand, IgG1 from hybridoma J2G7 showed an even stronger response to recombinant NS1 antigen, with a 5 to 100 fold strong affinity to NS1 protein compared to isotypes from other hybridomas .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: Thus, the unique physicochemical properties of the phage, in combination with modular display of peptides and proteins with known binding specificity, have spawned wholly novel materials with diverse applications. It is worth noting that the unusual biophysical properties of the filamentous phage can also be exploited in the study of structures of other macromolecules. Magnetic alignment of high-concentration filamentous phage in solution can partially order DNA, RNA, proteins, and other biomolecules for measurement of dipolar coupling interactions in NMR spectroscopy. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Thus, the unique physicochemical properties of the phage, in combination with modular display of peptides and proteins with known binding specificity, have spawned wholly novel materials with diverse applications. It is worth noting that the unusual biophysical properties of the filamentous phage can also be exploited in the study of structures of other macromolecules. Magnetic alignment of high-concentration filamentous phage in solution can partially order DNA, RNA, proteins, and other biomolecules for measurement of dipolar coupling interactions in NMR spectroscopy. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Because of their large population sizes, short generation times, small genome sizes and ease of manipulation, various filamentous and non-filamentous bacteriophages have been used as models of experimental evolution . The filamentous phage has additional practical uses in protein engineering and directed protein evolution, due to its unique tolerance of genetic modifications that allow biomolecules to be displayed on the virion surface. First and foremost among these applications is in vitro affinity maturation of antibody fragments displayed on pIII. Libraries of variant Fabs and single chain antibodies can be generated via random or sitedirected mutagenesis and selected on the basis", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Frequency and Fitness Consequences of Bacteriophage \u03a66 Host Range Mutations\nPassage: After a long period of steady decline, mortality due to infectious disease increased over the past several decades, largely because of the emergence of new infectious diseases including HIV . Of these new diseases, a disproportionate number have been viruses . Because of their high mutation rates and vast population sizes, viruses have higher probabilities of acquiring the requisite mutation allowing infection of novel hosts than do other types of pathogens . A common fear is that a highly transmissible and virulent virus will spread pandemically among humans, causing widespread mortality and economic damage. Thus, there is a strong motivation Title: Review article: the human intestinal virome in health and disease", "Passage: Phage-host interactions influence host and viral evolution. The ability of phages to transfer genes from one prokaryotic host to another can lead to increased diversification of viral species, and increased antibiotic resistance and/or induction of toxins or virulence factors in prokaryotes. 5 Some phages alter the antigenicity of their hosts by producing enzymes that modify the O-antigen component of lipopolysaccharides. 6 Modification of surface structures of prokaryotes has the potential to affect microbial interactions with the human host, and influence niche specialisation within the GI tract. 7 Presence of clustered regularly interspaced short palindromic repeats confers upon prokaryotes resistance to Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: research in therapeutics for chronic disease and the design of nanomaterials. Our comparatively detailed understanding of the interactions of model filamentous phage with their bacterial hosts has allowed researchers to harness the phage life cycle to direct protein evolution in the lab. Hopefully, deeper knowledge of phage-host interactions at an ecological level may produce novel strategies to control bacterial pathogenesis. While novel applications of the filamentous phage continue to be developed, the phage is likely to retain its position as a workhorse for therapeutic antibody discovery for many years to come, even with the advent of competing technologies.", "Title: Clinical aspects and cytokine response in severe H1N1 influenza A virus infection\nPassage: the same behavior against the time of symptom onset and admission. Title: The challenging management of Rift Valley Fever in humans: literature review of the clinical disease and algorithm proposal", "Passage: Soon after the onset of flu-like illness or acute hepatitis, patients may present bleeding from the nose or gums , hematemesis or melaena, petechial/purpuric rash or ecchymoses, menorrhagia, hematuria, or bleeding from venipuncture sites . Yellow fever-like expression were also reported with a first improvement at day 3 followed by a rebound of fever . Epistaxis is not considered a reliable sign of how serious the illness is . Thrombocytopenia is invariably present. Hepato-renal failure with jaundice, disseminated intravascular coagulation and encephalitis can be associated . Overall prevalence is estimated 1%, but prevalence was rather 10% in hospital cohorts . Title: Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection", "Passage: Two authors retrospectively reviewed the clinical and laboratory findings. For the review of the clinical features, initial symptoms such as fever, cough, sputum, rhinorrhea, sore throat, myalgia, headache, dizziness, vomiting, and diarrhea were recorded. In turn, patient symptom progression while under treatment was also reviewed. For review of the laboratory data, the hematological analysis of the white blood cell count, red blood cell count, hemoglobin level, hematocrit level, platelet count, neutrophil count and the biochemical analysis of alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase , creatine kinase , erythrocyte sedimentation rate , and C-reactive protein were recorded. Title: Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China", "Passage: According to the clinical data, the initial symptoms of A infection were primary fever, coughing, and fatigue. These findings are consistent with those of other published reports. The atypical symptoms recorded during the early stage of A patients were noteworthy. Two elderly patients were hospitalized due to neurological syndromes. The symptoms of A virus infection were covered up by the neurological syndromes which cause the delay for treatment. Given the high case fatality and features of patients in Guangzhou, it is important to remain on alert for those high risk people. Prior studies have suggested that the time of onset", "Title: Estimating the number of infections and the impact of non-\nPassage: Summary Title: CDC Summary 21 MAR 2020,\nPassage: Highlights of CDC\u2019s Response Title: CDC Summary 21 MAR 2020,\nPassage: COVID-19 Pandemic Title: CDC Summary 21 MAR 2020,\nPassage: Risk Assessment", "Title: Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children\nPassage: xacerbations are the primary cause of morbidity and mortality in children with asthma and occur despite current treatments. It has been established that the majority of exacerbations are provoked by viral respiratory infections, most notably rhinoviruses ; however, exacerbations also occur in the absence of infections 1,2 . Furthermore, even in children with severe asthma, the majority of respiratory infections do not progress to exacerbation 3 . The fundamental question of why some but not all colds lead to exacerbations has not been fully answered, and the similarities and differences between the mechanism of virus-associated and nonviral exacerbations are unknown. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the mechanisms underlying the development and acute exacerbation of chronic airway inflammatory disease is extensively studied for ways to manage and control the disease, a viral infection does more than just causing an acute exacerbation in these patients. A viral-induced acute exacerbation not only induced and worsens the symptoms of the disease, but also may alter the management of the disease or confer resistance toward treatments that worked before. Hence, appreciation of the mechanisms of viral-induced acute exacerbations is of clinical significance to devise strategies to correct viral induce changes that may worsen chronic airway inflammatory disease symptoms. Further Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection can exacerbate the disease. The review will serve to provide further understanding of viral induced exacerbation to identify potential pathways and pathogenesis mechanisms that may be targeted as supplementary care for management and prevention of exacerbation. Such an approach may be clinically significant due to the current scarcity of antiviral drugs for the management of viral-induced exacerbations. This will improve the quality of life of patients with chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further", "Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus\nPassage: S1 . The distribution of protein ratios are represented in Figure 1G as log 2 . The SILAC ratios indicate changes in protein abundance in the nucleolar fraction of Jurkat TAP-Tat cells in comparison with Jurkat TAP cells. The distribution of the quantified proteins followed a Gaussian distribution . A total of 49 nucleolar proteins exhibited a 1.5 fold or greater significant change upon Tat expression . Of these, 30 proteins were enriched, whereas 19 proteins were depleted. Cells displayed no changes in the steady state content of some of the major and abundant constituents of the nucleolus, including nucleophosmin Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture , we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: We labeled Jurkat TAP-Tat and Jurkat TAP cells with light and heavy isotope containing arginine and lysine, respectively. Following five passages in their respective SILAC medium, 85 million cells from each culture were harvested, pooled and their nucleoli were isolated as previously described . Each step of the procedure was closely monitored by microscopic examination. To assess the quality of our fractionation procedure, specific enrichment of known nucleolar antigens was investigated by Western Blot analysis . Nucleolin and Fibrillarin , two major nucleolar proteins known to localise to the granular component of the nucleolus, were found to be highly enriched Title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus", "Passage: Using a quantitative proteomic strategy based on an organellar approach, we quantified over 520 nucleolar proteins, including 49 proteins exhibiting a significant fold change. The extent to which the induced variations in the abundance of nucleolar proteins are biologically relevant and can affect cellular and/or viral processes remains to be determined. Nevertheless, the biological nature of the pathways and macromolecular complexes affected enable us to discuss their potential associations with HIV-1 pathogenesis.", "Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: pandemic, an estimated 35\u202f000 to 60\u202f000 ventilators would be needed, up to an estimated 7.3 billion surgical masks or respirators would be required, and perhaps most important, if vaccine development did not start before the virus was introduced, it was unlikely that a significant number of hospitalizations and deaths could be averted due to the time it takes to develop, test, manufacture, and distribute a vaccine. Title: Estimates of the Demand for Mechanical Ventilation in the United States During an Influenza Pandemic", "Passage: We present in Table 3 the calculated health outcomes , the number of ventilators needed , and number of deaths averted. The number of ventilators needed at peak range from approximately 7000 to 11 000 to approximately 35 000 to 60 500 . The total number of ventilator-related averted deaths range from approximately 35 000 to 55 000 to approximately 178 000 to 308 000 . Of note is that, for a given level of severity, there is some overlap in the ranges of estimates produced by the 2 CAR. For example, for high severity clinical attack scenarios, the number Title: Estimates of the Demand for Mechanical Ventilation in the United States During an Influenza Pandemic\nPassage: of deaths averted at 20% CAR ranges from approximately 119 000 to 206, 000, and for 30% CAR from 178 000 to 308 000 . Title: Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1)", "Passage: 19% reduction in the cumulative number of cases. With the same mask effectiveness but 25% of the population wearing N95 respirators, the total number of pandemic 2009 cases is reduced by almost 30% and with 50% of the population wearing masks, it results in over a 36% reduction in the number of cases.", "Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics\nPassage: Symptoms are common to each infection and manifest on a gradient. Generally, but far from always, influenza infection is more likely to result in a patient feeling so unwell as to take to their bed and have a fever, than RSV, an HRV, CoV or other common cold virus infection, during which daily life is usually less impacted. Title: Anxiety and Depression: Linkages with Viral Diseases", "Passage: the specific mechanisms can vary by viral illness. Mental conditions such as major depression can delay help-seeking or reduce the likelihood of detection of other health conditions including communicable diseases. 1 Depression and psychological stress have been shown to have a number of biological effects including reduced cell-mediated immunity and increased inflammatory processes. 3 A further issue is that some viral diseases can directly affect the brain and result in mood disorders or cognitive impairment. 1 Title: The protective and pathogenic roles of IL-17 in viral infections: friend or foe?", "Passage: Viral infections are common causes of both chronic and acute tissue pathology that create a significant health burden worldwide. For example, human papillomaviruses are the causative agents of epithelial hyperplasia of the skin and genital tract . Persistent infection of HPV can result in malignant lesions, the most common being cervical cancer, which had caused an estimated 0.6 million new cases in 2018 and contributed to more than 0.3 billion deaths . Hepatitis B virus and hepatitis C virus are the major causes of hepatitis and can progress to liver fibrosis, cirrhosis and eventually liver cancer . Human immunodeficiency virus Title: Macrophage Polarization in Virus-Host Interactions", "Passage: Viral infections acquired early in life are often associated with a higher rate of viral replication, a greater risk of persistent infection, and more severe disease compared with those acquired in later life. For example, children with perinatal HIV infections experience a rapid disease progression , more severe clinical signs with more opportunistic infections, and little probability of becoming long-term nonprogressors . In most cases of RSV and rhinovirus infections, where clinical signs are lacking or mild in adults, neonates generally show severe allergic inflammation and an asthmatic syndrome. This virus-mediated asthmatic syndrome in neonatal animals is promulgated by IL-4-mediated", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Vectored vaccines can be constructed to express full-length influenza virus proteins, as well as generate conformationally restricted epitopes, features critical in generating appropriate humoral protection. Inclusion of internal influenza antigens in a vectored vaccine can also induce high levels of protective cellular immunity. To generate sustained immunity, it is an advantage to induce immunity at sites of inductive immunity to natural infection, in this case the respiratory tract. Several vectored vaccines target the respiratory tract. Typically, vectored vaccines generate antigen for weeks after immunization, in contrast to subunit vaccination. This increased presence and level of vaccine antigen contributes to and Title: Viral vector-based influenza vaccines", "Passage: In the future, more novel vector-based influenza candidate vaccines will be developed and tested in clinical trials. There is potential for improvement by the modification of viral antigens, like the 'headless' or 'shielded' HA constructs, to broaden the reactivity of vaccine induced antibodies. In addition to modifying influenza virus antigens, post-translational modifications and modifications to promoter sequences could also alter and improve the immunogenicity. 226, 227 The biggest challenge of taking vector-based vaccines to the market may be obtaining approval from the regulatory authorities. Only when their safety and superiority over existing vaccine formulations have been demonstrated, implementation of these Title: Viral vector-based influenza vaccines", "Passage: viral vectors can easily be propagated to high virus titers and it is relatively easy to insert genes encoding antigens of choice into the vector. Viral vector technology also allows the production of modified influenza viral antigens in vivo. These modifications can improve the immunogenicity of the influenza viral proteins or alter the specificity of the immune response. In this review, we discuss reports on vectored influenza vaccines and discuss their advantages and disadvantages.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Abstract: BACKGROUND: Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo. PRINCIPAL FINDINGS: We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains pdm, H3N2, H5N1, Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: inhibited . Its antiviral activity is dependent on the type of polymer as well as the virus and the host cells and has been reviewed in . We published that iota-carrageenan is a potent inhibitor of hRV and influenza A replication and demonstrated the antiviral efficacy of iota-carrageenan against common cold viruses by intranasal application in several randomized, double-blind, parallel group, placebo-controlled clinical trials . The pooled analysis of two studies conducted in 153 children and 203 adults revealed that patients infected with any respiratory virus, who were intranasally treated with iota-carrageenan showed a 1.9 day faster recovery from common Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Two virus strains were selected for those experiments, one being the most sensitive to carrageenan pdm) and one being the least sensitive . In both cases the isobolograms show a synergistic interaction of carrageenan and Zanamivir . Thus, it was shown that Zanamivir and carrageenan target individual influenza viruses with different efficiencies, most probably due to their different antiviral strategies. As a result, the combination provides synergistic activity with higher protection against a broader spectrum of influenza virus strains than the individual compounds.", "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: Like SARS-CoV, 2019-nCoV induced pneumonia through respiratory tract by clinical observation. Therefore, the presence of viral antigen in oral swabs was used as detection standard for 2019-nCoV. Similarly, two times of oral swabs negative in a 24-h interval was considered as viral clearance by patients officially. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes\nPassage: In summary, we provide a cautionary warning that 2019-nCoV may be transmitted through multiple routes. Both molecular and serological tests are needed to definitively confirm a virus carrier. Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: We quickly identified the etiological agent, termed 2019-nCoV . The newly identified virus is an SARS-related virus but shares only 74.5% genome identity to SARS-CoV . We developed molecular detection tools based on viral spike genes. Our previous studies indicate that qPCR method can be used for the detection of 2019-nCoV in oral swabs or in bronchoalveolar lavage fluid .", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Notwithstanding this progress, there remains a disproportionate burden of disease in low-and middle-income countries, where more than 90% of pneumonia cases and deaths occur. The incidence in high-income countries is estimated at 0.015 episodes per child year, compared to 0.22 episodes per child year in low-and middle-income countries . On average, 1 in 66 children in high-income countries is affected by pneumonia per year, compared to 1 in 5 children in low-and middle-income countries. Even within low-and middleincome countries there are regional inequities and challenges with access to health care services: up to 81% of severe pneumonia deaths occur outside Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: odds of severe pneumonia by 2.7 times in low-and middle-income countries and 1.3 times in highincome countries. Markers of undernutrition are strong risk factors for pneumonia in low-and middle-income countries only, with highly significant odds ratios for underweight for age , stunting and wasting . Household crowding has uniform risk, with odds ratios between 1.9 and 2.3 in both low-and middle-income countries and high-income countries. Indoor air pollution from use of solid or biomass fuels increases odds of pneumonia by 1.6 times; lack of measles vaccination by the end of the first year of age increases odds of pneumonia by Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: a hospital . In addition to a higher incidence of pneumonia, the case fatality rate is estimated to be almost 10-fold higher in low-and middle-income countries as compared to high-income countries . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: 1.8 times . It is estimated that the prevalence of these critical risk factors in low-and middle-income countries decreased by 25% between 2000 and 2010, contributing to reductions in pneumonia incidence and mortality in low-and middle-income countries, even in countries where conjugate vaccines have not been available .", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV. Title: Host resilience to emerging coronaviruses", "Passage: Both SARS-CoV and MERS-CoV are typified by a rapid progression to ARDS, however, there are some distinct differences in the infectivity and pathogenicity. The two viruses have different receptors leading to different cellular tropism, and SARS-CoV is more ubiquitous in the cell type and species it can infect. SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4 . Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure . SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The 2-3 % prevalence of active MERS-CoV infections is not dissimilar to the hospital-based prevalence of other human CoVs. However, the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43 in other countries, and even above that for SARS-CoV; it is not a virus that could reasonably be described as a \"storm in a teacup\". It is the low transmission rate that has prevented worldwide spread, despite many \"opportunities\".", "Title: Estimating the number of infections and the impact of non-\nPassage: with a high level of uncertainty. Title: Estimating the number of infections and the impact of non-\nPassage: unable to conclude whether interventions may be different between countries or over time. Title: Estimating the number of infections and the impact of non-\nPassage: Many interventions have occurred only recently, and their effects have not yet been fully observed Title: Estimating the number of infections and the impact of non-\nPassage: to-fight-coronavirus-pandemic .", "Title: Lost in Translation (LiT)\nPassage: The pharmacokinetics of therapeutic antibodies has been extensively investigated . Native IgG antibodies have a half-life of 20-30 days, an attractive property of molecules that have to be administered parenterally. In the absence of target-mediated clearance, mAbs have a similar long half-life. mAbs are largely restricted to the plasma space because of their size and resulting slow diffusion. Antibodies and albumin are taken up through cell membranes by pinocytosis into vesicles where they bind to the MHC-related Fc receptor, FcRn. Binding to FcRn largely protects these proteins from intracellular catabolic degradation in the acidic endosome and allows recycling and release Title: Reassessing therapeutic antibodies for neglected and tropical diseases", "Passage: The other important factor to manage is the reduction of the frequency of administration, to make the prophylaxis useful in resource-poor settings. mAbs used in therapy are generally IgGs , which have plasma half-lives of 20 to 25 days in humans . Such antibodies can be used to provide several months of protection, as in the case of the once-per-season anti-RSV antibody MEDI8897 discussed earlier or the anti-calcitonin gene-related peptide fremanezumab, recently approved for prevention of migraines with a dose of 675 mg every 3 months. An alternative to simply increasing the dose would be increasing the half-life of the Title: Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities\nPassage: has a half-life of less than one day. Title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection", "Passage: Half-life studies in guinea pigs. Group of 4 guinea pigs were administered an IP injection of 1 mL purified equine antisera or F 2 . Blood samples were collected at 0, 1, 4, 8, 12, 24, 48, 72, 96, 120, 144 h post-injection, and sera were used for determination of neutralization titer against a recombinant HIV-1 virus pseudotyped with EBOV GP. The time range post-infection in which the titer decreases by 50% is considered the half-life. Each sample was performed in triplicate.", "Title: Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections\nPassage: RSV and RV infections to help lessen the burden of asthma development in childhood , however determining when the use of such prophylaxis is complicated . Thus, infants born preterm face serious consequences in response to respiratory viral infections. Title: Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial", "Passage: Respiratory syncytial virus is the most important agent to cause acute lower respiratory infection in young children; it also affects older adults and the immunocompromised . RSV infection elicits symptoms ranging from sinusitis and otitis media to bronchiolitis and pneumonia . In temperate climates, outbreaks occur in winter months. Tropical countries also have RSV seasons but with greater variation than in temperate locations . Title: The impact of respiratory viruses on lung health after preterm birth", "Passage: Several mechanistic pathways have been hypothesised to describe the potential role of severe RSVrelated respiratory illnesses in the pathogenesis of asthma and wheezing disorders later in life, including persistent activation of atypical immune responses and alterations to the structure and function of the developing airway . Mouse models have also demonstrated the ability of RSV to induce and maintain prolonged inflammatory responses leading to significant damage to the airway epithelium, as well as chronic airway remodelling and persistent airway hyperresponsiveness following the initial infection . Alterations of the local production of immunoregulatory cytokine, particularly interleukin-10, have also been identified as Title: The impact of respiratory viruses on lung health after preterm birth", "Passage: an important contributor to the subsequent development of recurrent wheeze and persistent airway hyperresponsiveness following RSV infection . The ability to alter local immune responses has also been proposed as a key mechanism, with some evidence describing the ability of RSV to redirect immune cells and maintain a low level of replication in immunologically privileged sites within the lung in order to avoid recognition by the immune system . Such alterations in immune responses sequentially result in latency and chronic persistence of the RSV genome within the lung for several weeks following the initial infection, with studies reporting significant association", "Title: Th17 profile in COPD exacerbations\nPassage: Th17 profile in COPD exacerbations of the mucus produced by goblet cells and less elimination of pathogens), metaplasia of squamous epithelial cells, hyperplasia of goblet-producing goblet cells and basal cells ), in addition to the loss of tight junctions that, under normal conditions, work as an impermeable barrier and protect the respiratory tract from pathogens, xenobiotics and other harmful particles. 9, 13 Once the damage is generated in airway epithelial cells, they secrete chemical mediators in order to generate and maintain an inflammatory response against foreign agents. 5 Cell death produced releases damage-associated molecular patterns such as heat shock proteins, Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection", "Passage: homeostasis Similar to intestinal mucosal epithelial cells, lung epithelial cells have developed many defence mechanisms to deal with environmental exposures. Increasing evidence shows that the UPR pathways interact with the recognition and handling of exogenous threats, like viruses. 44 The continuous epithelium in the airways acts as a physical barrier to keep the underlying immune system separated from exogenous air-borne pathogens. Ciliated cells continuously clear inhaled matter trapped by the mucus layer. Respiratory goblet cells synthesise and secrete the mucins, MUC5B and MUC5AC rather than MUC2. MUC5B/AC, and their glycoforms contribute to the elasticity and viscous nature of the mucus Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: . The massive cell death induced may result in worsening of the acute exacerbation due to the release of their cellular content into the airway, further evoking an inflammatory response in the airway . Moreover, the destruction of the epithelial barrier may cause further contact with other pathogens and allergens in the airway which may then prolong exacerbations or results in new exacerbations. Epithelial destruction may also promote further epithelial remodeling during its regeneration as viral infection induces the expression of remodeling genes such as MMPs and growth factors . Infections that cause massive destruction of the epithelium, such as Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Viral infections can cause the disruption of mucociliary function, an important component of the epithelial barrier. Ciliary proteins FIGURE 2 | Changes in the upper airway epithelium contributing to viral exacerbation in chronic airway inflammatory diseases. The upper airway epithelium is the primary contact/infection site of most respiratory viruses. Therefore, its infection by respiratory viruses may have far reaching consequences in augmenting and synergizing current and future acute exacerbations. The destruction of epithelial barrier, mucociliary function and cell death of the epithelial cells serves to increase contact between environmental triggers with the lower airway and resident immune cells. The opening", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: to 5 m people left Wuhan before the travel restrictions were imposed, are confirmed, the efficacy of these control measures will be more challenged. Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: By 26 January also, almost 50 million people in Wuhan and neighbouring cities had effectively been placed in quarantine while the WHO had determined that the event should not yet be declared as a Public Health Emergency of International Concern and had recommended no specific travel restrictions. The WHO have emphasised the importance of exit screening at ports in countries showing transmission of the novel coronavirus and have provided guidance for countries implementing entry screening at airports while acknowledging that evidence for the effectiveness of entry screening is equivocal. Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: Wuhan was about 11 million at the end of 2018 , the rate of people traveling out from Wuhan City would be 0.018 per day. However, we assumed that the normal population mobility before January 1 was 0.1 times as that after January 10. Therefore, we set the rate of people moving into and moving out from Wuhan City as 0.0018 per day . Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "Passage: Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London on their own homepage on 22 January 2020 that estimated the incidence based on three importation events at 4000 cases . Possible reasons for the slight difference include the number of travelers in the previous study was derived from airline passenger data and the assumed length of T was different. Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases as of 17 January 2020 and a University of Hong Kong group estimated 1343", "Title: In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues\nPassage: cytosol. Finally, if apoptosis was initially characterized by specific morphologic features, we must keep in mind that microscopic analysis of cells is still a major way for studying apoptosis, for instance, through microscopic analysis of chromatin condensation after DNA staining. Title: The Functional Properties of Preserved Eggs: From Anti-cancer and Anti-inflammatory Aspects", "Passage: Apoptosis is a procedural and physiological form of death. The characteristics of apoptosis include cell morphological changes, the formation of DNA fragments, etc. . Tumor development is not only the result of cell proliferation out of control, but more likely to be blocked due to apoptosis, cell proliferation and apoptosis caused by imbalance . Cell accumulation and aggressive development of viable cells into tumors will occur if cell apoptosis fails . Title: Evaluation of Ultra-Microscopic Changes and Proliferation of Apoptotic Glioblastoma Multiforme Cells Induced by Velogenic Strain of Newcastle Disease Virus AF2240", "Passage: Apoptotic cells, due to a change in membrane permeability, showed an increased up-take of the vital dye compared to live cells. The apoptotic cells with degraded DNA were represented in so-called \"sub-G1\" peaks on DNA histograms. The percentage of sub-G1 cells was measured. PI is added to discriminate late apoptotic or necrotic cells which had lost membrane integrity from early apoptotic cells which still had intact membranes by dye exclusion . Title: In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues", "Passage: Cell death typically occurs by necrosis, apoptosis, or autophagy. Concerning apoptosis, its characterization implies several criteria, such as changes in the nuclear morphology, especially chromatin fragmentation and condensation, and also the occurrence of apoptotic bodies that contain nuclear material, as well as reduction in cell volume and plasma membrane shrinkage. 9 Intrinsic or extrinsic stimuli can lead to apoptosis, and the 2 different pathways involve specific biochemical manifestations such as the activation of caspases. Caspase 9 and caspase 3 are classically activated in the intracellular pathway with a process of mitochondrial outer membrane permeabilization , whereas the extracellular pathway requires", "Title: Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus\nPassage: co- infections was HBoV, which was found in more than 70% of cases together with another virus, followed by coronaviruses HCoV OC43 and HCoV NL63 with 61% and 67%, respectively. On the other hand, the viruses most rarely seen in co-infections were influenza viruses A and B as well as RSV. Pearson correlation coefficients were calculated to examine the likelihood of co-infections of different viruses. The results of the analysis are summarized in Table 1 in S1 Table. Significant correlation was seen mostly for co-infections with RSV, however correlations were very weak and negative. This finding can probably be explained Title: Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection", "Passage: Forty-five patients had lower respiratory tract specimens sent for bacterial cultures. The 5 patients without these specimens were children who had difficulty in producing respiratory secretions, however, they appeared generally well with no evidence of pneumonia. Blood cultures were performed in 23 patients and Mycoplasma pneumoniae serology in 27 patients . Of the 50 H1N1 patients, 17 were coinfected with a second respiratory pathogen; 14 bacterial and only 3 viral. Mycoplasma pneumoniae was the commonest bacterial coinfection followed by Staphylococcus aureus , Klebsiella pneumoniae , Streptococcus pneumoniae , Moraxella catarrhalis , Pseudomonas aeruginosa , Streptococcus pyogenes and Streptococcus agalactiae . Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia", "Passage: Influenza viruses and picornavirus were the most commonly identified viruses, found in 38 and 22 patients, respectively. In nine patients, more than one virus was identified. In the 21 patients having undergone mPCR in both NP swabs and LRT specimen, the mPCR were discordant in ten patients, including eight patients with a NP mPCR positive and a LRT mPCR negative and two patients with a NP mPCR negative and a LRT mPCR positive. Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia", "Passage: A microbiological documentation was obtained in 144 patients. At least one bacterium was identified in 91 patients and at least one virus in 98 patients. Bacterial documentation was obtained in 56 patients who had not been exposed to antibiotics prior to referral, compared to 35 antibiotics-exposed patients . S. pneumoniae was the most commonly identified bacterium, found in 40 patients. Of these 40 patients, S. pneumoniae was cultured in blood in five patients. In 22 patients, more than one bacterial species was identified. Taken together, Pseudomonas aeruginosa and Enterobacteriaceae species were identified in nine patients of the bacterial group and", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway . Title: Th17 profile in COPD exacerbations", "Passage: In the past, it was believed that only bacteria were capable of generating exacerbations in patients with COPD. 48, 52 However, the occurrence of these in the winter and symptoms similar to cold led to the belief that viruses were also associated with the complications of this obstructive pathology of the airways. 53 On the other hand, viral infections of the respiratory tract have been shown to influence the lung microbiome in patients with COPD, which indicates that both microorganisms can coexist and predispose to exacerbations. 54 The most prevalent viruses during acute exacerbations of COPD are rhinovirus, coronavirus, influenza, Title: Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits", "Passage: In this study, the commonly identified viruses in patients with COPD exacerbations requiring ED visits were PIV3, Inf A virus, and human rhinovirus. This result was similar to the finding of Cameron et al from a study in Australia in which the most frequently detected viral etiologies were Inf A, PIV3, and rhinovirus. 21 In a recent review of eight studies, picornavirus was the most common virus in western countries and influenza virus was most common in Asia. 7 H. influenzae was the most common bacterial pathogen in COPD exacerbations in a previous study. 4 Pseudomonas aeruginosa and Klebsiella pneumoniae Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s ; with bacterial infections previously considered as the likely culprit for acute exacerbation . However, with the advent of PCR technology, more viruses were recovered during acute exacerbations events and reports implicating their role emerged in the late 1980s . Rhinovirus and respiratory syncytial virus are the predominant viruses linked to the development and exacerbation of chronic airway inflammatory diseases . Other viruses such as parainfluenza virus , influenza virus and adenovirus have also been implicated in acute", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The VEE replicon systems are particularly appealing as the VEE targets antigen-presenting cells in the lymphatic tissues, priming rapid and robust immune responses . VEE replicon systems can induce robust mucosal immune responses through intranasal or subcutaneous immunization , and subcutaneous immunization with virus-like replicon particles expressing HA-induced antigen-specific systemic IgG and fecal IgA antibodies . VRPs derived from VEE virus have been developed as candidate vaccines for cytomegalovirus . A phase I clinical trial with the CMV VRP showed the vaccine was immunogenic, inducing CMV-neutralizing antibody responses and potent T cell responses. Moreover, the vaccine was well tolerated and Title: Virus-Vectored Influenza Virus Vaccines", "Passage: SIN, SFV, and VEE have all been tested for efficacy as vaccine vectors for influenza virus . A VEE-based replicon system encoding the HA from PR8 was demonstrated to induce potent HA-specific immune response and protected from challenge in a murine model, despite repeated immunization with the vector expressing a control antigen, suggesting preexisting immunity may not be an issue for the replicon vaccine . A separate study developed a VEE replicon system expressing the HA from A/Hong Kong/156/1997 and demonstrated varying efficacy after in ovo vaccination or vaccination of 1-day-old chicks . A recombinant SIN virus was use as Title: Replication-Competent Influenza A Viruses Expressing Reporter Genes", "Passage: innate immune response . In addition, a HPAI virus was engineered to contain Venus . Mice infected with MA-HPAI-Venus resulted in a greater Venus-positive bronchial epithelium than MA-PR8-Venus as observed by two-photon microscopy . There were also increased numbers of Venus-positive macrophages in MA-HPAI-Venus infections, supporting findings that H5N1 HPAI viruses induce more severe inflammatory responses in the lung of infected mice than PR8 . Therefore, these studies demonstrated the utility of Color-flu for comparative studies of IAV pathogenesis . Title: Replication-Competent Influenza A Viruses Expressing Reporter Genes", "Passage: NS1, and were each separated by 2A self-processing sites . An HA-tag was also fused to NS1 to facilitate protein detection. The resulting PR8-NS1GFP virus replicated as efficiently as PR8 WT in vitro and retained reporter expression in 100% of plaques from 5 passages in MDCK-V cells, which have their IFN response blocked by stable expression of parainfluenza virus type 5 V protein . However, when passaged in parental MDCK cells, only 23% of plaques were GFP-positive after five passages . The recombinant virus was slightly attenuated in vivo but maintained 96.4% GFP-positive plaques when recovered five days post-infection from", "Title: Mammarenaviral Infection Is Dependent on Directional Exposure to and Release from Polarized Intestinal Epithelia\nPassage: Arenaviruses are enveloped viruses that have a single-stranded, bisegmented, ambisense RNA genome. The Large segment, encodes the matrix protein , and the RNA dependent RNA polymerase . The Small segment, encodes the nucleoproteins and glycoproteins . Initially, arenaviruses were thought to only infect mammals; however, recently arenaviruses have been identified as the causative agent of inclusion body disease in the boid family of snakes . Hence, Arenaviruses have been separated into two genera on the basis of their natural reservoir hosts; mammarenavirus, which infect mammalian hosts, and reptarenavirus which infect reptilian host species . Among the mammarenavirus genera, there is Title: Mimiviridae, Marseilleviridae, and virophages as emerging human pathogens causing healthcare-associated infections", "Passage: 2010 as an agent infecting marine zooplankton, and its genome consisted of \u2248730 kb of double-stranded DNA . Recently, Colson et al. , proposed assigning an official taxonomic rank to the NCLDVs as the order Megavirales, due to the large size of the virions and genomes of these viruses, and because of their common ancestral origin , , , . Families and genus belonging to this new tentative order are summarized in Table 1 , whilst a brief timeline of discoveries in this field is presented in Table 2 . During the last decade, plenty of other giant virus strains Title: Evidence for Novel Hepaciviruses in Rodents", "Passage: Placentalia evolutionary lineages according to . Major mammalian clades are identified at basal nodes of the Placentalia phylogeny: Afrotheria , Xenarthra, and Boreoeutheria, divided into the two superorders Euarchontoglires, and Laurasiatheria . Sampled mammalian orders are shown in boldface type. Orders containing novel hepaciviruses identified in this study are shown in red and boldface. Orders with known hepaciviruses are given in red. Numbers of extant families and species per order adapted from All rodent viruses had considerably fewer predicted glycosylation sites in their structural proteins, in particular their putative E2 proteins, as opposed to HCV. A detailed genome analysis is Title: Mammarenaviral Infection Is Dependent on Directional Exposure to and Release from Polarized Intestinal Epithelia\nPassage: further subdivision into the Old World LCMV-Lassa virus complex and New World , Tacaribe virus complex .", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: cold symptoms than placebo treated patients in the intention-to-treat population . The anti-influenza activity was shown by subgroup analysis of 49 influenza infected patients who benefited from a 3.3 days faster recovery from symptoms. The use of carrageenan nasal spray was associated with a significant reduction of the influenza viral load in nasal fluids and a significant increase in the number of virus free patients within the treatment period of 7 days. In good accordance Prieschl-Grassauer are co-founders of Marinomed Biotechnologie GmbH. Marinomed Biotechnologie GmbH had a role in study design, data collection and analysis, decision to publish, preparation of Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is Title: Effects and cost of glycyrrhizin in the treatment of upper respiratory tract infections in members of the Japanese maritime self-defense force: Preliminary report of a prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment clinical trial", "Passage: Upper respiratory tract infection is the most common human disease, accounting for at least half of all acute illnesses. 1 It has been estimated that two thirds to three fourths of URTIs are caused by respiratory viruses. 1 Although therapies have been developed for rhinoviruses 2 and influenza viruses, 3 specific antiviral therapy has not been developed for most respiratory viruses. Title: Effects and cost of glycyrrhizin in the treatment of upper respiratory tract infections in members of the Japanese maritime self-defense force: Preliminary report of a prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment clinical trial", "Passage: Because duties in military life are stressful, soldiers in poor health must be isolated and allowed to rest. Because most of the soldiers did not have their own house in the area, we chose to hospitalize them to have them rest. Accordingly, the results of this study should be interpreted with caution due to higher costs and shorter duration of illness than would be found in typical clinical practice due to the hospitalization of these patients. Because of the small sample size, further human studies are warranted to verify our results.", "Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats\nPassage: The replicase gene, ORF1ab, occupies~20.4 kb of the genome. The replicase gene, ORF1ab, occupies~20.4 kb of the genome. It encodes polyproteins 1a and 1ab, which could be cleaved into 16 non-structural proteins . The 3'-end of the cleavage sites recognized by 3C-like proteinase and papain-like proteinase were confirmed. The proteins including Nsp3 , Nsp5 , Nsp12 , Nsp13 , and other proteins of unknown function . The 7 concatenated domains of polyprotein 1 shared <90% aa sequence identity with those of other known alpha-CoVs , suggesting that these viruses represent a novel CoV species within the alpha-CoV. The closest assigned Title: Programmed \u22122/\u22121 Ribosomal Frameshifting in Simarteriviruses: an Evolutionarily Conserved Mechanism", "Passage: Arterivirus genomes vary in length between 12.5 and 15.5 kb and contain 10 to 15 known ORFs. All but two are located toward the 3= end of the genome and encode viral structural proteins that are translated from a nested set of subgenomic mRNAs . ORF1a and ORF1b, at the 5= end of the genome, comprise some three-quarters of the coding capacity and encode replicase-associated proteins. Translation of the genomic RNA yields the ORF1a polyprotein and, in addition, an ORF1ab fusion polyprotein following \u03ea1 PRF at the ORF1a/ORF1b junction . The two polyproteins are processed into individual functional nonstructural proteins Title: Molecular characterization and phylogenetic analysis of transmissible gastroenteritis virus HX strain isolated from China", "Passage: The replicase genes were composed of ORF1a and ORF1b, which contained a 43-nt common region and a \"slippery site\" . The ORF1a gene of TGEV-HX was predicted to encode a protein of 4,017 amino acids , while ORF1b was predicted to encode a 2,680-aa protein. Nucleotide sequence analysis indicated that there were no deletions or insertions in the ORF1ab region of the Miller 6 and Purdue TGEV strains. ORF3a and ORF3b of TGEV-HX were predicted to encode 72-aa and 244-aa proteins, respectively. No deletions or insertions were found in the ORF3a or ORF3b genes of TGEV-HX. The ORF7 gene of Title: Translational profiling of B cells infected with the Epstein-Barr virus reveals 5\u2032 leader ribosome recruitment through upstream open reading frames", "Passage: To analyse the aggregation of reads around start and stop codons , we considered the reads that were 27 and 28 nt in length. In the case of ORFs that are located in cellular transcripts, the counts of these particular reads were normalized by transcript length. The average normalized read coverage of nucleotide positions 20 bases up-and downstream of start and stop codons was then calculated.", "Title: Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus\nPassage: Strain 17V079 showed high similarity to other Belgian porcine kobuvirus isolates from 2014 and the Hungarian reference strain S-1/Hun/2017 . Furthermore, there was a high level of genetic variability between the 2014 Belgian porcine kobuvirus isolates, with nucleotide sequence identities ranging between 90.1 and 97.2%. A phylogenetic analysis, using the 3D gene of 17V079 and twelve Belgian isolates from 2014 , shows the Belgian strains clustering between strains from different geographical locations. Title: Molecular Epidemiological Investigation of Porcine kobuvirus and Its Coinfection Rate with PEDV and SaV in Northwest China", "Passage: To analyze the prevalence of the virus, we used MegAlign to analyze the amplified fragments of the 2C gene of 22 PKV strains . The viral samples shared 90.1%-100% nucleic acid sequence similarity. The 15 Gansu isolates shared 90.6%-99.3% nucleotide identity with strain swKoV CH441, which was isolated from northwest China and shared \u2265 90.1% nucleotide sequence identity with strain S-1-HUN. The strains from different regions of Gansu showed sequence variations, suggesting that they have different origins. Title: Molecular Epidemiological Investigation of Porcine kobuvirus and Its Coinfection Rate with PEDV and SaV in Northwest China", "Passage: the importation and exportation of pigs between regions. The samples from Pingliang and the PKV prototype strain, S-1-HUN, clustered on the same small branch. These results show that the 15 PKV identified in this study may have various genetic relationships with other porcine kobuviruses recorded in GenBank. These findings indicate that PKV displays good host adaption and is endemic to Gansu Province. Title: Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus\nPassage: Belgian isolates showed genetic moderate to high genetic variability, with nucleotide identities between 90.1 and 97.2%. Furthermore, they clustered diffusely between strains from different countries around the world, indicating that strains are not distinguishable based on their geographical origin.", "Title: Cytokines IL-17 and IL-22 in the host response to infection\nPassage: TIRAP and TRIF are recruited, and downstream signaling is initiated. The resulting activation of nuclear factor-\u03baB promotes transcription of a range of genes coding for proinflammatory cytokines, including IL-23, which trigger the production of IL-17 and IL-22 in cell subsets including Th17, \u03b3 \u03b4 T and ILC3. the gut and the lung . In the S. Typhimurium colitis model, Myd88 \u2212/\u2212 mice exhibit a delayed mucosal inflammatory response and blunted IL-17 and IL-22 levels when compared to wild-type controls . During gut infection with Citrobacter rodentium, Myd88 \u2212/\u2212 mice display increased mortality, intestinal pathology and systemic bacterial spread; whether this Title: Cytokines IL-17 and IL-22 in the host response to infection", "Passage: of S. Typhimurium colitis resulted in a blunted innate IL-17 response and an associated decrease in mucosal protection against the pathogen . A subset of LP CD4 + T cells that express IL-17 and IL-22 during the innate phase of infection with S. Typhimurium and C. rodentium has subsequently been identified and termed innate Th17 cells . Finally, two novel subsets of Th17 cells have recently been identified: a proinflammatory subset that produces GM-CSF and a regulatory subset that produces IL-10 . The role of these cell subsets in response to infection is unknown. Title: Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response", "Passage: p38 expression via ATF6 . On the other hand, pharmacological activation of XBP1 or overexpressing XBP1s with the ER stress inducers synergistically augments TLR-mediated IL-6 and TNF-\u03b1 productions. In addition, Kim et al. showed that ER stress inducer significantly augments LPS-induced proinflammatory cytokines and GSK-3\u03b2 activity in RAW264.7 macrophages and BMDM . Rao et al. demonstrated that Kupffer cells isolated from 4-PBA-treated ischemic liver or ATF6-downregulated Kupffer cells from ischemic liver produce significantly less TNF-\u03b1 and IL-6 after stimulation with LPS . Thus, ATF6 activation in ischemic liver induces enhancement of proinflammatory cytokine production of macrophage in response to TLR4. Title: Experimental murine acute lung injury induces increase of pulmonary TIE2-expressing macrophages\nPassage: or matrix-degrading proteins and immunomodulating cytokines .", "Title: Evolutionary Entropy Determines Invasion Success in Emergent Epidemics\nPassage: of emergent strains. Title: On the possible role of robustness in the evolution of infectious diseases\nPassage: evolve to change in biological populations. Title: Modelling and analysing the coexistence of dual dilemmas in the proactive vaccination game and retroactive treatment game in epidemic viral dynamics\nPassage: knowledge, no previous theoretical analysis has considered two provisions in the same context of the evolutionary game process. We also develop another new concept called the social efficiency deficit . Such a framework can explicitly elucidate the social dual-dilemma on both global and local time scales. Title: Evolutionary Entropy Determines Invasion Success in Emergent Epidemics\nPassage: -1 .", "Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: prediction, this novel orf8 has a high possibility to form a protein with an alpha-helix, following with a betasheet containing six strands ). Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: Orf8 orf8 is an accessory protein found in the Betacoronavirus lineage B coronaviruses. Human SARS-CoVs isolated from early-phase patients, all civet SARS-CoVs, and other bat SARS-related CoVs contain fulllength orf8 . However, a 29-nucleotide deletion, Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Bat which causes the split of full length of orf8 into putative orf8a and orf8b, has been found in all SARS-CoV isolated from mid-and late-phase human patients . In addition, we have previously identified two bat SARS-related-CoV and proposed that the original SARS-CoV full-length orf8 is acquired from these two bat SARS-related-CoV . Since the SARS-CoV is the closest human pathogenic virus to the 2019-nCoV, we performed phylogenetic analysis and multiple alignments to investigate the orf8 amino acid sequences. The orf8 protein sequences used in the analysis derived from early phase SARS-CoV that includes full-length orf8 , the mid-and late-phase Title: Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts", "Passage: ORF3 is predicted to be translated as a fusion with ORF1 via +1 ribosomal frameshifting at a UUU_CGU motif that is conserved in CBPV, AACV and LSVs 1 and 2 . As shown in Figure 4 , AACV is more closely-related to CBPV, with AACV+CBPV forming a sister group to LSV1 and 2. The topologies of phylogenetic trees constructed using alignments from either MUSCLE or COBALT were similar.", "Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data\nPassage: It is interesting to note that on average, our simple rules yielded a PPV of 0.84 and an NPV of 0.75. This means that on average, rules will correctly predict an abnormal laboratory result 5 times out of 6 and correctly predict a normal result 3 times out of 4. While not good enough to replace testing , these observations raise the question of how much better prediction can get. Integration of information not considered in the present study, including vital signs, chief complaints, and physical findings, may improve prediction by these methods. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: in this study we did not set out explicitly to make a statement about repeat laboratory testing, the appropriateness of which has been investigated elsewhere , these results suggest that repeat laboratory testing within one week does not always add information that could not have been anticipated from the previous result. Refining this observation using the same unbiased approach we have followed here is potentially an area for future investigation. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: Laboratory testing is the single highest-volume medical activity . Its main role is to help adjust the level of clinical suspicion of a diagnosis to help rule it in or out; it is also used for disease monitoring. In practice, the level of clinical suspicion and the probability of a given test result can be correlated: the higher the suspicion, the more likely it is that the result will confirm the diagnosis. Information that feeds into the clinical suspicionincluding the age and gender of the patient, prior diagnoses, and prior laboratory results-thus may also influence the test result. Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: We used four types of input-age, gender, diagnoses , and results of laboratory tests on blood samples added to the record in the seven days before a given test was ordered-to build simple, robust models for whether the result of a test would be within the reference interval or outside of it in a given direction , treating high and low results separately.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: There are several approaches to avoiding pre-existing vector immunity, such as the use of vectors derived from nonhuman sources, using human viruses of rare serotypes , heterologous prime-boost approaches , homologous reimmunization and removing key neutralizing epitopes on the surface of viral capsid proteins . The inhibitory effect of pre-existing immunity can also be avoided by masking the Ad vector inside dendritic cells . In addition, mucosal vaccination or administration of higher vaccine doses can overcome pre-existing immunity problems . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Microbiology 159 protein can downregulate immune responses in mice against the delivered antigen . Similar results were reported by Roberts et al. and Vindurampulle & Attridge . However, the latter authors found that the hypo-responsiveness could be largely eliminated by exposing animals to the foreign antigen prior to vectorpriming . Unfortunately, this would appear to be impractical for an immunization regimen! A study presented by Gahan et al. immunized mice with S. Typhimurium expressing C fragment of tetanus toxin antigen from an expression plasmid or as a DNA vaccine. Vaccinated mice developed humoral responses to LPS and tetC . Animals", "Title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling\nPassage: We then found that RIG-I and DDX60 colocalized after HTNV infection , implying that RIG-I and DDX60 might collaborate with each other to exert antiviral effects. To verify the antiviral role of RIG-I and DDX60, we designed a series of siRNAs targeting RIG-I and DDX60, and we selected the si-RIG-I-2 and siRNA-DDX60-1 with the highest knockdown efficiency by qRT-PCR in HUVECs . Simultaneously knocking down RIG-I and DDX60 significantly promoted HTNV NP expression , and knockdown of both of them could greatly affect IFN-\u2424 expression . Ectopic expression of either RIG-I or DDX60 inhibited viral replication, whereas overexpression of both Title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling", "Passage: detected, and it is unclear how host PRRs, especially RIG-I, recognize HTNV invasion . Here, considering the interaction of RIG-I and DDX60 and the effect of DDX60 on IFN-\u2424 production, we hypothesize that DDX60 might mediate RIG-I signaling activation upon HTNV infection, which requires further investigation. Title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling\nPassage: resulted in superior antiviral effects , indicating that efficient anti-HTNV responses might depend on the interactive effects of DDX60 and RIG-I. More importantly, RIG-I or/and DDX60 overexpression enhanced HTNV-induced IFN-\u2424 expression, and they had synergistic effects on IFN-\u2424 production . Consequently, NEAT1 might regulate IFN-\u2424 production by upregulating RIG-I and DDX60, and thus we were interested in how NEAT1 regulated RIG-I and DDX60 expression. Title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling", "Passage: RIG-I and DDX60 regulated by NEAT1-2 facilitate HTNV-induced IFN-\u2424 production. PRRs maintain a vital role in the promotion of IFN responses, and we conjectured that NEAT1 might amplify IFN responses by modulating these molecules. TLR3, TLR4, and RIG-I have been shown to recognize HTNV infection . DDX60 was recently reported as an important activator of RIG-I, but the antiviral effects of DDX60 remain a subject of debate , Here, we found that multiple Toll-like receptors like TLR1, TLR2, TLR3, and TLR4, as well as MDA5, were increased after HTNV infection, but none of them were influenced by silencing NEAT1-2 .", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: diarrheal disease was observed and astrovirus was shed in their stools . The virus can replicate in human embryonic kidney cells and was detected by electron microscopy . Adenoviruses are responsible for around 1.5%-5.4% of the diarrhea cases in children under the age of 2 years, reviewed in the literature . Of the 57 identified adenovirus types , only adenoviruses type 40 and 41 are associated with diarrhea . Next to these two types, adenovirus type 52 can also cause gastroenteritis , although it has been argued whether type 52 is actually a separate type since there is not sufficient Title: Enteric viruses in HIV-1 seropositive and HIV-1 seronegative children with diarrheal diseases in Brazil", "Passage: HAdV are frequently detected in outbreaks and sporadic DD in children under 5 years . HAdV belong to Adenoridae family, Mastadenovirus genus and are classified into seven species of HAdV with a total of 78 types of HAdV reported. HAdV are associated with different syndromes such as respiratory infections, conjunctivitis and DD. Enteric HAdV-F40 and F41 are the third most common cause of non-bacterial diarrhea among children. Other species such as A, B, C, G and D have also been detected in DD . Title: Human adenovirus type 7 infection causes a more severe disease than type 3", "Passage: Among the 8248 NPAs, 289 specimens were identified as positive for adenovirus, of which HAdV-3 and HAdV-7 were the most common types. As shown in Table 1 , age and gender distribution, underlying disease, and coinfection were comparable between HAdV-3 and HAdV-7. Co-infection with other respiratory viruses were observed in 57.5 and 40.5% of patients infected with HAdV-3 and HAdV-7, respectively. The most common clinical manifestations of HAdV-3 and HAdV-7 infections, such as cough, wheezing, croup, dry rales, moist rales and fever, including the peak of febrile body temperature , were not significantly different. In contrast, pneumonia was the most Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: distance to adenovirus type 41 . Adenoviruses can generally be propagated in cell lines; however, enteric adenovirus 40/41 are difficult to culture, reviewed in the literature .", "Title: A Simulation Optimization Approach to Epidemic Forecasting\nPassage: amplitude and durations of three pre-2006 influenza pandemic events in England and Wales. They used regression techniques to fit a time-series disease incidence curve obtained from a traditional differential equation epidemiology model to the mortality and influenza-like illness data for the three pandemics. This technique required estimation of nine parameters, including the reproduction number. The model also assumed knowledge of the natural history of the disease from detailed epidemiological studies in the early stages of the pandemic. Title: On epidemic modeling in real time: An application to the 2009 Novel A (H1N1) influenza outbreak in Canada", "Passage: The accuracy of any modeling is highly dependent on the epidemiological characteristics of the outbreak considered, and most epidemic curves exhibit multiple turning points during the early stage of an outbreak. While these may be due to stochastic variations in disease spread, and changes in either surveillance methods or case definitions, turning points may also represent time points where epidemics transition from exponential growth processes to processes that have declining rates of growth, and thus may identify effects of disease control programs, peaks of seasonal waves of infection, or natural slowing of growth due to infection of a critical fraction Title: A Simulation Optimization Approach to Epidemic Forecasting", "Passage: This study extends the application of the individual-based epidemiology model to forecasting of the epidemic infection curve . The epidemic curve is defined as the daily or weekly number of cases observed for the duration of the epidemic . We seek to forecast the time at which the epidemic peaks, the number of infected individuals at the peak and the cumulative infected counts. These measures provide a summary of the epidemic curve and are important to public health officials. An accurate forecast of these measures at a regional level would enable local public health officials to evaluate intervention strategies and Title: An object simulation model for modeling hypothetical disease epidemics \u2013 EpiFlex", "Passage: 9a shows a histogram of cities in which 1,000 manifesting cases are first occurring. Figure 9b shows a histogram of cities in which the first occurrences of at least 10 incubating cases of influenza appear. Note that in Figure Upper graph shows graphed points for population versus total morbidity as estimated from immunity Figure 6 Upper graph shows graphed points for population versus total morbidity as estimated from immunity. Lower two graphs show sample graphs for 3500 and 35000 . The green line in the lower two graphs shows immunity. One vertical demarcation on the x axis is one month", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The first validated diagnostic test was designed in Germany. Corman et al. had initially designed a candidate diagnostic RT-PCR assay based on the SARS or SARS-related coronavirus as it was suggested that circulating virus was SARS-like. Upon the release of the sequence, assays were selected based on the match against 2019-nCoV upon inspection of the sequence alignment. Two assays were used for the RNA dependent RNA polymerase gene and E gene where E gene assay acts as the first-line screening tool and RdRp gene assay as the confirmatory testing. All assays were highly sensitive and specific in that they did Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: There are eleven studies that focus on SARS-CoV diagnostic testing . These papers described diagnostic methods to detect the virus with the majority of them using molecular testing for diagnosis. Comparison between the molecular test and serological test showed that the molecular test has better sensitivity and specificity. Hence, enhancements to the current molecular test were conducted to improve the diagnosis. Studies looked at using nested PCR to include a pre-amplification step or incorporating N gene as an additional sensitive molecular marker to improve on the sensitivity . Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The Hong Kong University used two monoplex assays which were reactive with coronaviruses under the subgenus Sarbecovirus . Viral RNA extracted from SARS-CoV can be used as the positive control for the suggested protocol assuming that SARS has been eradicated. It is proposed that the N gene RT-PCR can be used as a screening assay while the Orf1b assay acts as a confirmatory test. However, this protocol has only been evaluated with a panel of controls with the only positive control SARS-CoV RNA. Synthetic oligonucleotide positive control or 2019-nCoV have yet to be tested . Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: The existing practices in detecting genetic material of coronaviruses such as SARS-CoV and MERS-CoV include reverse transcription-polymerase chain reaction , real-time RT-PCR , reverse transcription loop-mediated isothermal amplification and real-time RT-LAMP . Nucleic amplification tests are usually preferred as in the case of MERS-CoV diagnosis as it has the highest sensitivity at the earliest time point in the acute phase of infection . Chinese health authorities have recently posted the full genome of 2019-nCoV in the GenBank and in GISAID portal to facilitate in the detection of the virus . Several laboratory assays have been developed to detect the novel", "Title: Baculovirus-based Vaccine Displaying Respiratory Syncytial Virus Glycoprotein Induces Protective Immunity against RSV Infection without Vaccine-Enhanced Disease\nPassage: , anti-CD44 or anti-CD43 . Both antibodies were purchased from BD PharMingen . After staining, cells were fixed in PBS-2% paraformaldehyde, and events were acquired using a FACSCalibur flow cytometer . To enumerate the number of cytokine-producing cells, intracellular cytokine staining was performed as described elsewhere . In brief, 2\u00d710 6 freshly explanted lung lymphocytes were cultured in a culture tube. Cells were left untreated or stimulated with 10\u03bcM G peptide and then incubated for 5 h at 37 o C in 5% CO2. Brefeldin A was added for the duration of the culture period to facilitate intracellular cytokine accumulation. Title: Baculovirus-based Vaccine Displaying Respiratory Syncytial Virus Glycoprotein Induces Protective Immunity against RSV Infection without Vaccine-Enhanced Disease", "Passage: Cells were then stained for surface markers, washed, fixed, permeabilized with fluorescence-activated cell sorter buffer containing 0.5% saponin , and stained for cytokines. The antibodies used were anti-IFN-\u03b3 or anti-IL-17A . Dead cells were excluded on the basis of forward and side light scatter patterns. Data were collected using CELLQuest software and analyzed with CELLQuest and WinMDI version 2.9 software . Lung supernatants were also collected for analysis with the FlowCytomix , according to the protocol. Kits containing antibody beads were used to measure cytokine levels in each of the samples. Title: Baculovirus-based Vaccine Displaying Respiratory Syncytial Virus Glycoprotein Induces Protective Immunity against RSV Infection without Vaccine-Enhanced Disease", "Passage: Respiratory syncytial virus is the most important viral pathogen of causing serious bronchiolitis and pneumonia in infants and young children worldwide. RSV is also receiving increasing recognition as an important cause of lower respiratory tract illness in immunocompromised patients, the young children, and the elderly . Despite the importance of RSV as a respiratory pathogen, there is no licensed vaccine currently available against RSV infection. Title: Neonatal Genetic Delivery of Anti-Respiratory Syncytial Virus (RSV) Antibody by Non-Human Primate-Based Adenoviral Vector to Provide Protection against RSV", "Passage: data showed that the anti-RSV IgG was detected in the BAL after intranasal administration but not intramuscular administration at the time of peak serum IgG levels . The intranasal administration route may be advantageous through the production of the neutralizing antibodies directly by the respiratory mucosal cells, the primary target of RSV. Future studies should examine the cellular source of the antibody within the respiratory mucosa, and include more analyses of the nose-associated lymphoid tissue immune cells.", "Title: First Complete Genome Sequence of a French Bovine coronavirus Strain\nPassage: Text: B ovine coronavirus belongs to the Nidovirales order, the Coronaviridae family, the Coronavirinae subfamily, and the Betacoronavirus . Its genome is a single-stranded, linear, and nonsegmented RNA of around 31 kb. BCoV is responsible for respiratory and enteric diseases in cattle, particularly during winter . To date, the 19 complete BCoV genome sequences available in GenBank databases originated from the United States or Asia. Here, we report the first complete genome sequence of a BCoV detected in France. Title: Bovine respiratory syncytial virus: infection dynamics within and between herds", "Passage: The impact of herd size on the prevalence of BRSV was examined by classification according to the number of cow-years in the herd. Of the 117 herds, 20 had a size of 50 or more cow-years and were classified as large herds, and 96 of them had less than 50 cow-years and were classified as small herds. The exact number of cow-years was missing for one herd which was excluded from the calculations on herd size. Contingency analysis was performed with number of cowyears \u226550 and <50 as the independent variables and serostatus from sampling one to two as the Title: Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses", "Passage: PRRSV RNA was detected in particle sizes ranging from 0.3 to 0.7 \u03bcm and in particles ranging from 2.1 to 10 \u03bcm . However, there was higher viral load of PRRSV in larger particles compared to smaller ones . Title: Self-assembly into virus\u2013like particles of the recombinant capsid protein of porcine circovirus type 3 and its application on antibodies detection\nPassage: The diameter of the circovirus is around 17 nm, similar to beak and feather disease virus , bat circovirus and PCV2. The morphological study of PCV3 has not be conducted, whether 10 nm particles is the true size of the virus remains to be determined. Previous studies have shown that expressing the full-length PCV3 cap gene and NLS domains presenting within the N-terminal arginine rich motif may cause misfolding of the protein and induce formation of circular virus complexes of 10-12 nm . Other groups have published that, different sizes of VLPs appear in different expression systems , a number", "Title: Vaccines for the future: learning from human immunology\nPassage: vaccinated with the Yellow fever vaccine YF-17D . These studies have shown that it is possible to predict the efficacy of the vaccine by measuring the transcriptome of PBMCs few hours after vaccination. Interestingly, the predictive innate immune signatures were not obvious, involving genes, such as EIF2AKA that had not been associated with the generation of adaptive responses before. The new biological information discovered by systems biology approaches helped to better understand the mechanism of action of the vaccine and can now be exploited to rationally design improved vaccine adjuvants targeting the 'protective' genes or pathways . Title: Clinical vaccine development", "Passage: Despite the historic achievement of Jenner, because of insufficient fundamental knowledge about microbiology, no new vaccines were developed for more than a century. In the late 19th century, heroic scientists such as Louis Pasteur, Robert Koch, Emil von Behring, and Paul Ehrlich discovered the basic principles and developed the experimental methodology of immunology and immunotherapy that led to the next stage of vaccinology . Following their seminal investigations, many other studies were performed and led to improved regulations , which resulted in the development of valid live and/or attenuated vaccines. New vaccines against diseases including rabies, typhoid fever, diphtheria, shigellosis, Title: Vaccines for the future: learning from human immunology", "Passage: been highlighted by several experts in the field that if we want to understand the cellular correlate of vaccine protection it is not sufficient to count the frequencies of antigen-specific T cells in response to vaccination but it is important to assess their quality: the cytokine that they make, their differentiation state and the receptors expressed on the surfaces that may predict their localization in case of infection . Title: Vaccines for the future: learning from human immunology", "Passage: Preventive vaccines have been a major success in medicine in the last century. However there are still many infectious diseases that cause millions of deaths every year worldwide. Conventional approaches have failed to develop effective vaccines against these pathogens. However there is great hope for the future that is based not only on new technologies available for vaccine development, but also in an increased ability to interrogate the human immune responses and integrate complex readouts through computational methods.", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: The analysis of the focus group data was undertaken by a single researcher who was neither present at the focus groups nor had read any preliminary findings. This work was verified by the focus group facilitators to ensure that any \"contextual richness\" had not been missed in the data. Thematic analysis was used to identify themes and concepts across the entire data set to \"identify repeated patterns of meaning\" . The process involved working through the six phases of thematic analyses as identified by Braun and Clarke . Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The study was part of a rapid response initiative; therefore focus groups were selected as the most efficient means of data collection in the time available. Eight semi-structured focus groups were recruited between May and July 2010 comprising 7 to 13 participants each and lasting approximately 1 hour. Separate focus groups were conducted for each of the target groups with a total of 80 participants representative of five target populations groups identified in consultation with Ministry of Health staff: M\u0101ori, Pacific Peoples, children , general population, and vulnerable people with chronic conditions (defined as those who are eligible for subsidised Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's", "Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice\nPassage: The ability of human adenoviruses to induce strong innate and adaptive immune responses makes them powerful adjuvants that facilitate the immune response against an encoded antigen. Recombinant adenoviruses have been shown to elicit significant immune responses to bacterial , viral and tumour-associated antigens . While these results are encouraging, immunity eventually develops against virus capsid proteins. This severely reduces the immunogenicity of adenovirus-based vaccines in mice, , primates and humans . This problem is also significant since a large portion of the Western world has marked levels of anti-adenovirus serotype 5 antibodies and is also prominent in regions of sub-Saharan Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: previously exposed to adenovirus will respond to these immunization regimens. Title: Viral vector-based influenza vaccines\nPassage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: Taken together, these data support the notion that the exposition of the virus capsid proteins facilitates the immune response against the encoded antigen. Optimization of PEGylation chemistries and/or densities on adenovirus-based vaccine that promote and strengthen protective immune responses following oral immunization is currently underway.", "Title: Human H5N1 influenza infections in Cambodia 2005\u20132011: case series and cost-of-illness\nPassage: The median delay between the onset of HPAI symptoms and hospitalisation of seven days was similar to that reported for other countries in the region, six days in Indonesia and Vietnam and five days in Thailand . Children aged \u22645 years were hospitalised more quickly than adults although it still took an average of 5.7 days for children to be admitted. A study of 13 countries from Asia and the Middle East, also found more prompt hospitalisation of children \u22645 years . Due to the reliance on hospitals to manage viral diagnostic testing, it was instigated a median of six Title: Human H5N1 influenza infections in Cambodia 2005\u20132011: case series and cost-of-illness", "Passage: symptom onset, whilst adults 18 years and older were hospitalised after 9.7 days. No patients received their first dose of oseltamivir within the recommended 48 hours from the onset of symptoms. Title: Geographic Distribution and Risk Factors of the Initial Adult Hospitalized Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in Mainland China\nPassage: Of the 885 hospitalized adult cases, 590 experienced a delay#2 days in hospital admission, 815 completely recovered and were free of H1N1-associated symptoms on discharge whereas 70 were censored . The median time from illness onset to hosptial discharge was 7 days . Title: Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study\nPassage: Fatal case-patients had an onset of illness from 1 July 2009 to 14 September 2009. Duration of illness prior to death ranged from 1 day to 27 days, with a median of 11 days. Sixty-two per cent of case-patients were hospitalised prior to death.", "Title: Reovirus Activates a Caspase-Independent Cell Death Pathway\nPassage: Induction of necroptosis by any of the pathways described above requires the formation of the ripoptosome or a similar multiprotein complex . This 2-MDa signaling complex is comprised of three core components, RIP1, caspase-8, and FADD . In addition, it also contains regulators such as cFLIP, cIAP1, cIAP2, and XIAP. The decision between cell survival, apoptosis, and necroptosis occurs at the level of the ripoptosome and depends on the activity of caspase-8 . When procaspase-8 is sufficiently processed and caspase-8 activity is high, apoptosis ensues. In contrast, when caspase-8 activity is lower due to heterodimerization of caspase-8 with cFLIP L Title: MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice", "Passage: Necroptosis is a newly discovered pathway of programmed cell death . Unlike the uncontrolled accidental cell death, necroptosis is regulated by classical necrosome comprising receptor-interacting protein kinase 1 , RIPK3, mixed-lineage kinase domainlike protein through TNF/TNFR1 signaling or other stimuli . In addition, DNA-dependent activator of IFN regulatory factors is also identified to induce the RIPK1-independent RIPK3-dependent necroptosis by recognizing viral double-stranded DNA and recruiting RIPK3 directly through the RHIM domain . MLKL is the executor of necroptosis after being recruited and phosphorylated by RIPK3. MLKL recruits Ca 2+ and Na + ion channels and form pores at the plasma Title: Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms", "Passage: Programmed necrosis or \"necroptosis\" has been described more recently as a highly regulated, caspase-independent cell death with similar morphological characteristics as necrosis . Necroptosis is a receptor-mediated process. It is induced downstream of the TNF receptor 1 and is dependent on the activity of the receptor interacting protein kinase 1 and RIPK3. Recent studies has uncovered a key role for RIPK1 as the mediator of necroptosis and a regulator of the innate immune response involved in both inflammation and cell death . Evidence from SCI studies show that lysosomal damage can potentiate necroptosis by promoting RIPK1 and RIPK3 accumulation . Title: Reovirus Activates a Caspase-Independent Cell Death Pathway", "Passage: death in these cells . The effect of Nec-1 on reovirusinduced cell death was independent of its effect on the blockade of indoleamine 2,3-dioxygenase , an additional target of Nec-1 , since direct inhibition of IDO using 1-methyl-Ltryptophan did not prevent reovirus-induced cell death . The capacity of reovirus to establish infection and grow in Nec-1-treated cells was not affected . Nec-1 also did not diminish caspase-3/7 activity in T3D-infected cells . These data suggest that RIP1 kinase activity is required for reovirus-induced cell death.", "Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management\nPassage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5 Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In Jeddah between March and July 2014 , there was a rapid increase in MERS cases, accompanied by intense screening; approximately 5,000 samples from in and around the region were tested in a month yielding around 140 MERS-CoV detections . Among 5,065 individuals sampled and tested across the KSA between October 2012 and September 2013,108 detections were made in a hospital-centric population which included hospitalized cases , their families and associated HCWs . Among the detections, 19 were HCWs and 10 were family contacts . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Fig. 3 Monthly detections of MERS-CoV and of cases who died with some dates of interest marked for 2012 to 4 th September 2015. An approximation of when DC calving season and when recently born DCs are weaned is indicated. Spring and summer in the Arabian Peninsula are also shaded. Note the left-hand y-axis scale for 2014 and 2015 which is greater than for 2012/13. Sources of these public data include the WHO, Ministries of Health and FluTrackers . Earlier and subsequent versions of this chart are maintained on a personal blog . Modified and reprinted from Mackay IM,", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Hantavirus diseases of man have long been suspected of having an immunopathogenic basis in part because of their relatively long incubation period of 2-3 weeks and the observed temporal association between immunologic derangements and the first appearance of signs and symptoms of hantavirus illness. HFRS and HCPS share many clinical features, leading many investigators to consider them to be, in essence, different manifestations of a similar pathogenic process, differing mainly in the primary target organs of disease expression . The pathogenesis of hantavirus infections is the topic of a continuously-updated review in the series UpToDate . Title: Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France", "Passage: on the observation that for many viruses, pathogenicity is linked to a disproportioned innate immune response able to induce damages to the host what may be the reason of an immune mediated pathogenesis in hantavirus infection . In this case, the V10D mutation could be responsible for a lower activation of the innate immune system and thus reduced pathogenic infection in humans. It would be important to clarify whether these subtle differences between genetically closely related hantaviruses may induce very different virulence. Currently, no reverse genetic system is available for hantaviruses to investigate this point and only comparative genomics may Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: The protracted incubation period associated with hantavirus disease gives the host considerable time to mount a mature immune response against the virus. Thus, in contradistinction to infections of comparable severity and related symptomatology associated with arenaviruses and filoviruses, hantavirus infections of humans are associated with antibody responses of significant titer by the time symptoms commence. Despite this observation, it appears to be possible that natural variation in individual neutralizing antibody responses among patients with SNV infections can be linked to disease severity, suggesting that administration of antiviral antibodies could prove effective therapeutically . In the case of ANDV infection, new Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Innate immune mechanisms. The nature of interactions between hantavirus pathogen-associated molecular patterns with the pattern recognition receptors of susceptible endothelial cells are beginning to be clarified. The prototypical HTNV appears to be recognized by TLR-3 . Such an infection has consequences such as increased expression of HLA-DR in dendritic cells and differentiation of monocytes toward dendritic cells .", "Title: A multidimensional classification of public health activity in Australia\nPassage: A 'resources' class was elevated in importance when consultations reinforced the importance of the many types of infrastructure on which today's public health relies: physical infrastructure , organisational infrastructure , logistical infrastructure -systems that are seen by some as 'joined up' resources. There were diametrically opposed views of whether infrastructure was a subclass of resources or vice versa. In the short term this has been dealt with by amalgamating the two into a 'resources and infrastructure' class. Title: Factors that enable effective One Health collaborations - A scoping review of the literature", "Passage: Resource mobilization and allocation during an event, relies heavily on the starting conditions, as well as the communication, leadership and management during the process of collaboration. A number of authors pointed to the importance of being able to mobilize both the material and human resources. Once again, the involvement of diverse stakeholders, the use of MCMs and management systems such as ICS were attributed with the ability to draw upon existing resources. Processes characterized as successful included establishing a supply chain with standardized access, delivery, allocation and flow . Human resource mobilization benefited from online recruitment as well as reflexive Title: Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories", "Passage: For this comparative analysis we focus on four key health system resources: antiviral drugs , hospital beds, mechanical ventilators and healthcare workers , chosen due to their critical importance for responding to pandemic influenza. These resources, along with over 50 other resource items relating to health system infrastructure, equipment, materials, and human resources, were selected through a systematic literature review and a Delphi consensus process by a panel of 24 experts, as described in . Quantities of these resource items were enumerated during March to September 2009 through questionnaires administered to hospitals and health offices in all districts of each Title: A multidimensional classification of public health activity in Australia", "Passage: Public health experts expressed diametrically opposed views as to whether 'infrastructure' represented aggregates of 'resources', or whether 'resources' were in fact a subclass of 'infrastructure'. An inclusive approach was adopted, in line with development principle above, with the relevant class termed 'Resources and Infrastructure', and its subclasses capturing both compound and unitary elements .", "Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus\nPassage: The cotton rat was first used in polio research in the 1930s , and throughout the last century, it has proven to be an excellent model for biomedical research . Historically in biomedical research, the mouse has been exploited as the default animal model. This is in part due to its well defined immunological and genetic information, costeffectiveness, and abundant inbred strains and research reagents. However, the use of mice as models to study infectious diseases has its limitation since mice are not naturally infected by most human pathogens. On the other hand, cotton rat is susceptible to many human Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: Text: The cotton rat was first used in polio research in the 1930s , and throughout the last century, it has proven to be an excellent model for biomedical research . Historically in biomedical research, the mouse has been exploited as the default animal model. This is in part due to its well defined immunological and genetic information, costeffectiveness, and abundant inbred strains and research reagents. However, the use of mice as models to study infectious diseases has its limitation since mice are not naturally infected by most human pathogens. On the other hand, cotton rat is susceptible to many Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: Abstract: Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, Title: Identification and characterisation of the CD40-ligand of Sigmodon hispidus", "Passage: A number of methods and reagents have been developed for the analysis of immune responses in cotton rats over the last decade. Up to date, more than 200 genes encoding cytokines, chemokines, cell surface markers and regulatory molecules have been cloned, with various related research reagents being commercially available. As a result, the use of cotton rats in pathogenesis studies addressing mechanistic questions has significantly increased. Nevertheless, the gene encoding CD154 and CD40 ligand , remains elusive.", "Title: A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs)\nPassage: According to our results, the only acceptable match out of all available class A pairs was that between the captopril binding sites of the proteins with the PDB IDs 2x8z and 4dpr. Some further class A pairs were assigned high scores, but the alignment of the corresponding binding sites did not correctly superpose the counterpart ligand atoms, but physicochemically similar ligand moieties . Some results can be explained by the way similar binding site pairs were extracted. Sometimes, the ligand atoms \"observe\" similar interaction partners, but the 3D orientation of these atoms is rather different as presented in S8 Table. Title: A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs)", "Passage: assigned based on a 5 \u00c5 radius of all ligand atoms. Subsequently, the C\u03b1 atoms and all atoms of the binding site-defining residues were aligned using the \"match\" command of UCSF Chimera . The mean RMSD values, standard deviations, minima and maxima of all pairwise comparison were calculated to characterize the binding site flexibility. For the data set of identical structures, Tanimoto coefficients based on the ECFP4 fingerprints were calculated in a pairwise manner for all groups using KNIME . Title: A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs)", "Passage: The same holds true for the interaction-based methods. The question arises of whether unstable interactions of the ligand with the protein of interest vanish in some ensemble structures. The interaction patterns of the underlying NMR ensembles confirm this assumption. It indicates that only a small portion of all observed interactions remain stable within the ensemble. Such changes do not influence residue-and surface-based methods to a major extent, but they negatively affect comparison methods that rely on a distinct set of interactions. An inclusion of interaction strengths for an interaction-based comparison method could lead to improved overall performance. Again, the inclusion Title: A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs)", "Passage: sites of the abovementioned captopril binding proteins with a good agreement of the ligand atom positions in the alignment. Shaper-derived alignments also do not provide perfect alignments of ligand atoms for the best-scored hits, although ligand moieties with a similar physicochemical nature overlap. These results indicate that a visual inspection of the best ranked binding site pairs is a crucial step to assess the significance of the identified matches. Binding site similarity can only be a reasonable explanation for the binding of identical or similar ligands if the corresponding ligand atoms overlap in the superposition.", "Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Text: Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus . Evolutionary analyses have shown that bats and rodents are the gene sources of most \u03b1CoVs and \u03b2CoVs, while avian species are the gene sources of most \u03b4CoVs and \u03b3CoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. The best-known examples include severe acute respiratory syndrome CoV which emerged in China in 2002-2003 to cause a large-scale epidemic with about 8000 Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: Text: Coronaviruses belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales. A human coronavirus caused the severe acute respiratory syndrome coronavirus outbreak in 2003. Most recently, an SARS-related CoV was implicated as the etiological agent responsible for the outbreak in Wuhan, central China. This outbreak is estimated to have started on 12th December 2019 and 17,332 laboratory confirmed cases with 361 deaths as of 3rd February 2020 in China . The virus has spread to 23 other countries by travellers from Wuhan . Typical symptoms are fever, malaise, shortness of breath and in severe cases, pneumonia Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: According to what has been reported , COVID-2019 seems to have similar clinical manifestations to that of the severe acute respiratory syndrome caused by SARS-CoV. The SARS-CoV-2 genome sequence also has \u223c80% identity with SARS-CoV, but it is most similar to some bat beta-coronaviruses, with the highest being >96% identity .", "Title: Markers of exacerbation severity in chronic obstructive pulmonary disease\nPassage: Finally, the compatibility between the studies of COPD exacerbation that we analysed may have been limited by substantial variations in the time and location of studies. Exacerbations are more likely in summer but many studies failed to report the time of year or the time period for study implementation. Thus, seasonal effects, combined with the low incidence of exacerbations per patient, could represent an inherent bias. In addition, different institutions probably had different standards with respect to diagnosis and management of COPD exacerbations when these studies were performed. Such variations may also explain any observed inconsistencies in our findings. However, Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: As observed in The additional online file, there was a scarcity of information particularly for biomarkers at different exacerbation levels. It is also unclear to us whether any of the variables that changed with exacerbation severity are causally-related. Hence, longitudinal studies and/or less restrictive eligibility criteria would be needed to address all these questions. One difficulty in tackling such problems is the enormous amount of time and expense involved in implementing such studies. In addition, the current methods for data analysis in clinical studies have limitations imposed by the assessment of the reduction in frequency or total suppression of exacerbation Title: Markers of exacerbation severity in chronic obstructive pulmonary disease", "Passage: Lastly, our findings were obtained from COPD patients that had experienced at least one exacerbation during the study assessment period. In the same studies, there were also patients who did not experience an exacerbation. This indicates that a fraction of COPD patients may be regarded as being susceptible to an exacerbation whereas another fraction is 'exacerbation-free'. It would be interesting to determine how the variables we identified in our study change in the latter patient group according to FEV 1 . Some published studies have stratified COPD patients on the basis of exacerbation frequency; this is generally done by categorising Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: mice with this construct induced robust neutralizing antibody responses and protected mice from challenge with a heterologous virus, A/Hong Kong/1/1968 . Replication defective rAd5 vaccines expressing influenza HA have also been tested in humans. A rAd5-HA expressing the HA from A/Puerto Rico/8/1934 was delivered to humans epicutaneously or intranasally and assayed for safety and immunogenicity. The vaccine was well tolerated and induced seroconversion with the intranasal administration had a higher conversion rate and higher geometric meant HI titers . While clinical trials with rAd vectors have overall been successful, demonstrating safety and some level of efficacy, rAd5 as a vector Title: Viral vector-based influenza vaccines", "Passage: prime followed by rAd5 boost regimen was used, inducing protection against infection with the homologous virus in all cases. 216 Title: Rodents Versus Pig Model for Assessing the Performance of Serotype Chimeric Ad5/3 Oncolytic Adenoviruses\nPassage: Cancers 2019, 11 6 infection with Ad5/3 was observed only in porcine PK15 cells and human A549 controls . Title: Viral vector-based influenza vaccines", "Passage: testing rAd5 vectors expressing the HA genes from avian viruses of the A, A and A subtype 199, 206 combinations thereof) showed that mice could be protected from homologous challenge infection. Heterosubtypic immunite was never observed, however it was shown that simultaneous vaccination with 5 different rAd5-HA vaccines was feasible and protected from challenge infection with viruses of all subtypes under investigation. 207 Comparable to expressing modified influenza antigens in other vectors with the goal of inducing universal influenza immunity , a rAd expressing a modified HA gene was constructed. This HA gene was modified to shield the immunodominant head", "Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal\nPassage: Global estimates of pertussis show the highest childhood burden in Southeast Asia . In this region, maternal pertussis vaccination during pregnancy may be a way to protect infants, similar to the approach using tetanus toxoid vaccine. However, globally only 1 population-based estimate of pertussis in infants from birth has been conducted , and surveillance and laboratory capabilities in Asia are lacking . The World Health Organization recently recommended that countries using whole cell pertussis vaccines continue to do so in light of recent data indicating that acellular pertussis vaccines are less effective than whole cell pertussis vaccines . Population-based data Title: Neonatal Pertussis, an Under-Recognized Health Burden and Rationale for Maternal Immunization: A Systematic Review of South and South-East Asian Countries", "Passage: countries . While data from 2008 show that there were 148,095 reported cases globally , the WHO estimated that there were 16 million cases of pertussis globally, of which 95% were in developing countries in the same year . In India, the average number of cases reported per year between 2000 and 2016 is . Title: Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal", "Passage: Abstract: BACKGROUND: Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal. METHODS: Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, Title: Neonatal Pertussis, an Under-Recognized Health Burden and Rationale for Maternal Immunization: A Systematic Review of South and South-East Asian Countries", "Passage: In Indonesia, an increase in the number of pertussis cases was noted since 2012 ; the majority of the cases were reported in infants aged 0-5 months . Similar findings based on physical symptoms were documented in 2007 during a large pertussis outbreak in India with high rates of suspected pertussis in infants aged 0-1 year . In contrast, during 2011-2014, in Nepal, the incidence of polymerase chain reaction -confirmed pertussis was 13.3 cases per 1000 infant-years. This surveillance was conducted during a period of low pertussis transmission . Notably, in another study from Nepal in which an influenza vaccine", "Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: The mean hospital stay was 13.8 days with a median of 9 days . The mean stay by age group was: 0-4 years 7. A total 1125 cases had information on antiviral treatment, 1113 received oseltamivir and 12 zanamivir. 863 of these cases received treatment in the first 48 h after admission. Antiviral treatment administered before 48 h on admission was associated with a shorter length of stay Nosocomial cases were excluded from the analysis . Title: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey\nPassage: The median duration of hospitalization was three days . This result was unaffected by the patients' age . Parental request/non compliance 2 Title: What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data", "Passage: reduction of the mean duration of stay from 6.83 to 4.58 days. Title: Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008\nPassage: Duration of hospital stay varied from < 1 to 96 days , duration of PICU stay was between < 1 and 50 days . In 70% of patients, PICU admission occurred at the day of hospital admission or within one day afterwards . In one child, the influenza infection was assumed to be nosocomial, with start of influenza symptoms and transfer to the PICU 9 days after initial hospitalisation due to complicated pneumonia caused by Mycoplasma pneumoniae.", "Title: Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses\nPassage: ranged from 36%-60% overall, which is alarmingly high compared with all previous outbreaks of human cases of seasonal influenza in the United States, for which the CFR has ranged from 0.04%-1.0% . This high level of illness severity and high mortality rate was unexpected and increased disease burden, resulting in concern among clinicians and public health officials; however, the risk factors that are most highly associated with the deaths from avian influenza were not clear. Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features", "Passage: In 2007, 86 human cases with 59 mortalities were reported from nine countries: Cambodia, China, Egypt, Indonesia, Laos, Myanmar, Nigeria, Pakistan and Vietnam . A total of 442 confi rmed cases of avian fl u have been reported till 24 September 2009 from the above-mentioned 15 countries with 262 deaths .The mortality rate is around 60% which is very high. Infection with H5N1 in humans has so far remained confi ned to individuals with close contact with infected birds or surfaces or objects heavily contaminated with their droppings. This virus has not acquired the ability for sustained human to human Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features", "Passage: 90% of patients infected with H5N1 are less than 40 years old with a median age of 18 years . The mortality is highest among the 10-19 years age group and lower in people more than 50 years old. The reason for lower infection rate and mortality in older people has not been ascertained. Title: Human H5N1 influenza infections in Cambodia 2005\u20132011: case series and cost-of-illness\nPassage: with HPAI in Cambodia to the end of 2011 is notably higher than the rate of 58.7% reported globally . It is also higher than other case fatality rates reported in Southeast Asia, with the exception of Laos where the only two reported cases have proved fatal . Since data collection ceased, at the end of 2011, until April 2013 there have been 13 further cases of H5N1 diagnosed in Cambodia, with 11 fatalities, bringing the CFR to 87% . The 100% CFR of those under the age of 18 years also contrasts with the findings of the study multi-country", "Title: Deep Sequencing to Identify the Causes of Viral Encephalitis\nPassage: RNA was extracted from frozen brain using a Qiagen RNeasy Blood and Tissue kit. RNA was extracted because all viruses utilize RNA at some point during their lifecycle. The extracted RNA was DNase treated per kit instructions and submitted for sequencing at the University of Utah Next Generation Sequencing Shared Resource Facility. Prior to sequencing, RNA was analyzed on an Agilent Bioanalyzer Nanochip and evaluated for RNA size, abundance and integrity as previously described. [ Title: Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces", "Passage: Total RNA was prepared from human cell lines and tissue samples from 13 different human adult tissue types, i.e. blood, brain, breast, colon, epithelium, kidney, lymphoma, lung, liver, muscle, prostate, rectum and thyroid. RNA purification was performed by cesium chloride ultracentrifugation according to Chomczynski and Sacchi , by phenol-based extraction methods , or silica gel-based purification methods according to the manufacturer's instructions with some modifications. Material was maintained at \u00c080 C with minimal handling. RNA extraction was carried out in an RNase-free environment . Title: Evaluation of potential reference genes in real-time RT-PCR studies of Atlantic salmon", "Passage: Samples from eight organs, i.e. gills, liver, brain, head kidney, spleen, thymus, white muscle and posterior intestine, were dissected out and immediately frozen in cryo tubes in liquid N and stored at -80\u00b0C before RNA extraction. The RNA extracted from three spleen and four head kidney tissue samples were of low quality, and we had to redo the sampling from four individuals, These tissue samples Stability of six genes in gills of Atlantic salmon during smoltifi-cation calculated with the geNorm software were stored on RNA later at -20\u00b0C before further processing. Title: Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation", "Passage: Preliminary processing of raw reads was performed using Casava 1.8 . Reads were aligned to the human genome build 38 with STAR v2.4.0. Taffeta scripts were used to assess quality of aligned reads, which included quantifying number of mapped reads, junction spanning reads, assessing 5\u2032 and 3\u2032 bias, and insert size distribution. For each sample, ERCC Spike-in dose response curves were created following the manufacturer's protocol . Because samples with low RIN had characteristics similar to those of higher quality and duplicate samples were highly correlated, we combined data for duplicate samples and included them in further analyses. Raw read", "Title: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example\nPassage: totally susceptible population . When R 0 is greater than one, there is a likelihood that the infection will to continue to spread; however if R 0 is less than one, then the infection will eventually die out. For this reason, estimating the basic reproduction number is paramount for assessing the effectiveness of different intervention strategies. Title: Self-Interest versus Group-Interest in Antiviral Control", "Passage: Here we focus on a basic model for a large well-mixed population. To evaluate whether successful invasion of the pathogen is possible we calculate the reproduction number , which gives the number of new infections caused by a single infected individual in a population of uninfected individuals in the early stages of an outbreak . If R 0 .1 the pathogen can invade a population in which it is not yet present, while it cannot if R 0 ,1. In the case that the pathogen-induced mortality is such that it hardly affects the infectious period, the reproduction number is given Title: Estimating the number of infections and the impact of non-\nPassage: intervention. Afterwards, if the Rt is above 1, the number of infections will starts growing again. Title: Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic", "Passage: Consider someone who the index case in their household; they would be expected to infect R G = 1.21 people out of their household and m 2 = 0.64 within their household. This validates assumed proportions of transmission within and between households from earlier simulation studies . The sum of these is greater than R since the reproduction number R is an average over different generations of infection within the household. For this value, the estimate of R which takes into account local saturation effects was determined numerically to be R = 1.79. Fig 3 shows that for all values", "Title: Epithelial Cell Apoptosis and Neutrophil Recruitment in Acute Lung Injury\u2014A Unifying Hypothesis? What We Have Learned from Small Interfering RNAs\nPassage: sepsis , and ARDS all showed evidence of decreased apoptosis. The anti-apoptotic effect of ARDS plasma on PMNs appears to be mediated through the GM-CSF receptor . In sepsis, the delay in apoptosis was associated with a decrease in caspase-3 and -9 activity and a prolonged maintenance of the mitochondrial membrane potential . The delay of PMN apoptosis also involved the active regulation of CXC receptors by PMNs themselves . However, controversy persists as to whether this sustained activation actually contributes to organ injury. Activated PMNs have been shown to exert damaging effects in the lungs . However, following G-CSF Title: Epithelial Cell Apoptosis and Neutrophil Recruitment in Acute Lung Injury\u2014A Unifying Hypothesis? What We Have Learned from Small Interfering RNAs", "Passage: Regulation of PMN Apoptosis. Neutrophils, once mature, exhibit a constitutive form of programmed cell death with a life span between 6 to 12 h in circulation. Under normal circumstances, activated PMNs are eliminated fairly quickly once the invading pathogen has been cleared. Several inflammatory agents, such as LPS, TNF, IL-8, IL-6, IL-1, Granulocyte colony-stimulating factor -CSF), etc., can inhibit PMN apoptosis . The delayed apoptotic response provides PMNs with a longer life span, which, in turn, allows them to accumulate at local tissue sites of inflammation/infection. In this respect, PMNs obtained from patients following major trauma , burn injury , Title: Epithelial Cell Apoptosis and Neutrophil Recruitment in Acute Lung Injury\u2014A Unifying Hypothesis? What We Have Learned from Small Interfering RNAs", "Passage: survival rate was observed, associated with an increased dissemination of the bacteria . It should be noted that Fas-mediated apoptosis in the lung appears to be modulated by several factors such as surfactant protein A, Angiotensin II, transforming growth factor -beta, decoy receptor 3, etc. , and that other apoptotic pathways, for example, mediated by TNF-\u03b1 or mitochondria , appear to play a role under certain circumstances, too. Title: The Evolving Role of Neutrophils in Liver Transplant Ischemia-Reperfusion Injury\nPassage: with formyl peptide receptor 2 and prompts neutrophil apoptosis . Clearance of apoptotic neutrophils by macrophage efferocytosis may then switch macrophages to anti-inflammatory IL10/TGF\u03b2 dominant phenotype, leading to tissue-repairing environment as well as Treg dominated immune tolerance.", "Title: UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection\nPassage: Previous studies have demonstrated resolution of virus-induced liver disease after 5 days of MCMV infection in WT mice . Therefore, given the impaired inflammatory responses observed in the absence of endosomal TLR signaling, liver sections prepared from 3d and WT mice that were uninfected or infected for 3, 5, or 7 days were hematoxylin and eosin stained to evaluate pathology. The histological appearance of liver sections from uninfected 3d and WT mice appeared comparable . By day 3 post-MCMV infection, clusters of infiltrating cells or inflammatory foci, which have been shown to coincide with sites of MCMV antigen expression , Title: Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver", "Passage: livers 7 days after the injection. In all cases, n = 3 mice per group. HCV core protein expression was sustained for at least 600 days after poly injection. Immunohistochemical analysis revealed that most hepatocytes expressed the HCV core protein within 6 days after injection. Liver sections from CN2-29 /MxCre mice after the poly injection. Infiltrating lymphocytes were observed on days 6 and 180; Hepatocellular carcinoma was observed on day 360. In contrast, these pathological changes were not observed in CN2-29 /MxCre mice after the injection. The inset image shows abnormal mitosis in a tumor cell. Hepatocyte swelling and abnormal Title: Prevalence of human herpesvirus 6 antibodies and DNA in allogeneic stem cell transplant patients: two-year single centre experience", "Passage: The collection of plasma samples from all patients for HHV-5 PCR investigations, according EBMT guidelines, began at a median of 3 days after transplantation and lasted until a median of 105 days . Routine collection of plasma samples was performed once a week until the 100th day after allogeneic HSCT, thereafter once every two weeks, up to 180th day after HSCT. The median number of blood samples per patient was 12 . A total of 294 samples from the 26 patients were collected. For the purpose of recent study, viral DNA was extracted from 200 \u00b5l of each plasma sample Title: Early-Life Hepatitis E Infection in Pigs: The Importance of Maternally-Derived Antibodies\nPassage: samples were also taken from piglets at the ages of 1, 6, 10 and 14 weeks for serological analysis.", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: work became the basis for construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires . Using hybrid M13 phage displaying Co 3 O 4 -and gold-binding peptides on pVIII as a scaffold to assemble nanowires on polyelectrolyte multilayers, Nam et al. produced a thin, flexible lithium ion battery, which could be stamped onto platinum microband current collectors . The electrochemical properties of such batteries were further improved through pIII-display of single-walled carbon nanotube-binding peptides , offering an approach for sustainable production of nanostructured electrodes from poorly conductive starting materials. Phagebased nanomaterials have found applications in cancer imaging Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: work became the basis for construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires . Using hybrid M13 phage displaying Co 3 O 4 -and gold-binding peptides on pVIII as a scaffold to assemble nanowires on polyelectrolyte multilayers, Nam et al. produced a thin, flexible lithium ion battery, which could be stamped onto platinum microband current collectors . The electrochemical properties of such batteries were further improved through pIII-display of single-walled carbon nanotube-binding peptides , offering an approach for sustainable production of nanostructured electrodes from poorly conductive starting materials. Phagebased nanomaterials have found applications in cancer imaging Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For more than a decade, interest in the filamentous phage as a building block for nanomaterials has been growing because of its unique physicochemical properties, with emerging applications in magnetics, optics, and electronics. It has long been known that above a certain concentration threshold, phage can form ordered crystalline suspensions . Lee et al. engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields. Taking advantage of the ability to display substrate-specific peptides at known locations on Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: For more than a decade, interest in the filamentous phage as a building block for nanomaterials has been growing because of its unique physicochemical properties, with emerging applications in magnetics, optics, and electronics. It has long been known that above a certain concentration threshold, phage can form ordered crystalline suspensions . Lee et al. engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields. Taking advantage of the ability to display substrate-specific peptides at known locations on", "Title: Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential\nPassage: For the full collection of clinical isolates that had whole genome short-read sequencing data , reads were aligned to the 3D7 reference genome using bowtie2 . Samples with less than 10 million reads mapping to the reference were excluded, as samples with less than this amount had reduced coverage across the genome. Bam files were processed according to GATK's Best Practices documentation . Joint SNP calling was done using Haplotype Caller . Because clinical samples may be polyclonal , diploid calls were initially allowed, followed by calling the major allele at positions with heterozygous calls. If the major allele was Title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture\nPassage: assembled chromosomes. Title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture", "Passage: GRCh38p1.chrY , but absents from HuRef.chrY and YH.chrY that did not use BACs for sequencing and assembling, they are unlikely shared. Title: Generation and comparative genomics of synthetic dengue viruses\nPassage: Three DENV cDNA samples were sequenced and analyzed: one of the samples was the wildtype strain, with the WT sequence used as a reference genome for NGS analysis. The two synthetic variants of the virus were synthesized using two different methods . The WT sequence can be found in Additional file 1, section 8. Sequencing libraries were prepared using the INCPM DNA-seq protocol, and sequenced 2 \u00d7 150 on an Illumina MiSeq nano v2 PE150. Sequenced reads were mapped to a reference genome using BWA MEM v0.75 . Among all read-pairs with the same alignment, a single representative read was", "Title: Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated \u201cHuman Immune System\u201d Mice\nPassage: were also used to screen for TT-specific antibodies. After coating, the plates were washed in ELISA wash buffer . A PBS solution containing 4% of milk was used as a blocking agent, before adding serial dilution of HIS mouse plasma or cell culture supernatants . Enzyme-conjugated detection antibodies were added at a dilution of 1:2500 for HRP-conjugated anti-IgG and a dilution of 1:5000 for HRP-conjugated anti-IgM . Then, TMB substrate/stop solution was used for the development of the ELISA assay. Title: A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve", "Passage: Antibody binding competition. A final concentration of 5 mg ml \u00c0 1 H3-BR07 or H5-VN04 protein immobilized on ELISA plates were incubated with two fold serial dilution of 3I14 Fab, ranging from 80 to 0.3 nM and mixed with other scFvFc Abs at 5 nM. After co-incubation for 1 h, the binding of scFvFc Abs was detected using horseradish peroxidase-conjugated anti-human CH 2 antibodies and measured using Super AquaBlue ELISA substrate on the POLARstar Omega Microplate Reader . Title: A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve", "Passage: were added to each well at 5, 1, 0.2 and 0.04 mg ml \u00c0 1 final concentration. After one-hour, Jurkat effector cells were added for 6.0 \u00c2 10 4 /well to assay plates in low IgG Serum assay buffer and incubated for 6 h. The supernatants were recovered by centrifugation at 300g and measured luminescence using Bio-Glo Luciferase Assay kits by the POLARstar Omega Microplate Reader . Data represent a representative experiment from three independent experiments, and all tests were performed in triplicate. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Using 4D5, 2B5, 1F1, 2B8, 4F9, and 4E11 as capture antibodies, detection antibodies were coupled to biotin-NHS ester at 4\u00b0C for 3 h according to the manufacturer's instructions. Unincorporated biotin was removed by Desalt spin column . Immunologic reactions were reported by Streptavidin-HRP and Super Signal ELISA Femto Maximum sensitive substrate. Purified goat-anti mouse antibody was used as a positive control.", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The analysis of the focus group data was undertaken by a single researcher who was neither present at the focus groups nor had read any preliminary findings. This work was verified by the focus group facilitators to ensure that any \"contextual richness\" had not been missed in the data. Thematic analysis was used to identify themes and concepts across the entire data set to \"identify repeated patterns of meaning\" . The process involved working through the six phases of thematic analyses as identified by Braun and Clarke . Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: The study was part of a rapid response initiative; therefore focus groups were selected as the most efficient means of data collection in the time available. Eight semi-structured focus groups were recruited between May and July 2010 comprising 7 to 13 participants each and lasting approximately 1 hour. Separate focus groups were conducted for each of the target groups with a total of 80 participants representative of five target populations groups identified in consultation with Ministry of Health staff: M\u0101ori, Pacific Peoples, children , general population, and vulnerable people with chronic conditions (defined as those who are eligible for subsidised Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: and how these influence the process warrant a more in-depth examination.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The key limitations of genetic material detection are the lack of knowledge of the presence of viable virus, the potential cross-reactivity with non-specific genetic regions and the short timeframe for accurate detection during the acute infection phase. The key limitations of serological testing is the need to collect paired serum samples from cases under investigation for confirmation to eliminate potential cross-reactivity from non-specific antibodies from past exposure and/or infection by other coronaviruses. The limitation of virus culture and isolation is the long duration and the highly specialized skills required of the technicians to process the samples. All patients recovered. Title: Multiplexed Genetic Analysis Using an Expanded Genetic Alphabet", "Passage: addition, these technologies are not easily amenable to automation. Many hospitals and clinics currently send molecular diagnostics tests to large reference laboratories. This is in part attributable to the limitations described. Because there are benefits in having local laboratories perform diagnostic tests , there appears to be a need for molecular testing methods that circumvent the limitations posed by current testing methods. Title: Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences\nPassage: We have tested the upper limits of DNA that LAMP reactions can tolerate and found that up to 200 ng DNA in a 20 \u03bcl reaction, positive detection is reproducible. Above this DNA level, reactions become unreliable . Title: A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences", "Passage: sensitivity for many lengths of overlap and find that a length of at least 50 nucleotides is required before the method becomes effective. As this length increases to 300 nucleotides , the method becomes a very powerful diagnostic tool as measured by an area under the curve equal to 0.89. The estimate of this method's sensitivity and false discovery rates for an overlapping gene detection method is a strength, as although sensitivity can be calculated for other methods, false discovery estimation is often neglected and rarely reported due to a lack of negative controls. When it is reported, it is", "Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: reported. On January 15, 2020, the Centers for Disease Control and Prevention confirmed the first known imported case of 2019-nCoV in the US state of Washington. The patient had recently returned from Wuhan City, where he likely contracted the disease. Chicago health authorities reported a second US case on January 24, 2020. This was quickly followed by additional imported cases reported in Orange and Los Angeles Counties, California on January 26, 2020. Additional suspected cases continue to be evaluated. On January 30, 2020, the CDC reported the first local transmission in the US between members in a household. On the Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: Text: 2019 Novel Coronavirus is a novel respiratory disease first reported in Wuhan, Hubei Province, China in December 2019. 1 Chinese health officials were originally investigating a sudden increase in cases of pneumonia which were later determined to be linked to 2019-nCoV. While most cases originated within mainland China, the disease spread to neighboring countries including Taiwan, Thailand, South Korea, and Japan, and later to the United States, Europe, and Australia. A near real-time updated tracking website for cases and locations worldwide, along with reported deaths is available. 2 Chinese health authorities have sequenced 2019-nCoV and freely shared its genetic Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: Abstract: 2019 Novel Coronavirus is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be Title: Note from the editors: novel coronavirus (2019-nCoV)", "Passage: Text: The situation has continued to evolve rapidly since then and just a few weeks later, as at 23 January, 614 laboratory-confirmed cases and 17 deaths have been reported including some cases detected outside mainland China . Meanwhile, on 7 January 2020, the novel coronavirus, currently named 2019-nCoV, was officially announced as the causative agent by Chinese authorities . In order to support public health action, viral genome sequences were released by Chinese researchers on 10 January and 2 days later, four further sequences were also made available on the Global Initiative on Sharing All Influenza Data . While more", "Title: Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis\nPassage: We also observe positive selection for dinX on the branch leading to the pathogenic Mycobacteria in our d N /d S analysis . Most organisms use specialized DNA polymerases that are able to catalyze translesion synthesis across sites of damage, including the dinB group of Y family polymerases. There are two dinB-family polymerases in Mtb . Unlike in other bacteria, dinX and dinP expression are not dependent on recA, the SOS response, or the presence of DNA damage, and could therefore serve a novel yet uncharacterized role in Mtb . Title: Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection", "Passage: ranked much lower among the non-DNA damaging compounds , signifying a high specificity of ProTINA predictions . Equally important, ProTINA was able to accurately identify the direction of the drug-induced alterations caused by the DNA damaging compounds. The signs of protein target scores from ProTINA indicated drug-induced enhancement of CDKN1A, PCNA and GADD45A, and attenuation of CCNB1, AURKA and PLK1 , consistent with the expected response of these proteins to DNA damage in Figure 3 . Title: T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders", "Passage: Retinopathy. In retinopathy, SYVN1, syniviolin 1, is involved in endoplasmic reticulum associated degradation. SYVN1 confers diabetic retinopathy resistance. Yang S et al. described this with expression analysis and found lower expression of SYVN1 in diabetic mice 127 . TXNIP, thioredoxin interacting protein, is a thioloxidoreductase. It protects cells from oxidative stress. TXNIP plays crucial role in the inflammation and retinal injuries in early stages of DR 128 . Title: Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection\nPassage: involved in the overall DNA damage repair and its associated pathways . As depicted in Figure 4B , ProTINA ranked these proteins much higher than De-MAND and DE analysis, with DE performing the poorest among the methods considered.", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: HCPS, a disadvantageous consequence of the close anatomic juxtaposition of the two organs. Thus, at least three classes of potential mechanisms, some overlapping and all certainly nonexclusive of the others, could be presumed to underlie the pathogenesis of HCPS. These include: Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: severe forms of HFRS and HCPS have begun to achieve sufficient mass as to induce, through PAMP-PRR interactions and other means, the expression of proinflammatory cytokines . For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed, and yet it is often not appreciated that the expected preferential tissue tropism of HFRS-associated viruses and their HCPS-associated counterparts for the renal and pulmonary beds, respectively, is not as one would predict through the manifestations of the two diseases. Title: Vaccines and Therapeutics Against Hantaviruses", "Passage: Increased capillary leakage due to hantaviral infection is the basic pathogenic feature for both HFRS and HCPS. Therefore, treatment strategies improving microvascular endothelial cell function seem to be feasible in mitigating disease severity and reducing mortality . Hantavirus-disturbed vascular function is a multifactorial event whose complicated mechanisms still need to be elucidated, and two kinds of hypothesis have been developed. The vascular endothelial growth factor theory was first proposed and studied in depth. VEGF binding to VEGF receptor 2 could activate SFK signaling, which may result in dissociation, internalization, and degradation of VEcadherin. Altered expression and localization of VE-cadherin contributed Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: By the time symptoms appear in HCPS, both strong antiviral responses, and, for the more virulent viral genotypes, viral RNA can be detected in blood plasma or nucleated blood cells respectively . At least three studies have correlated plasma viral RNA with disease severity for HCPS and HFRS, suggesting that the replication of the virus plays an ongoing and real-time role in viral pathogenesis . Several hallmark pathologic changes have been identified that occur in both HFRS and HCPS. A critical feature of both is a transient capillary leak involving the kidney and retroperitoneal space in HFRS and the lungs", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: of improved or altered binding, roughly mimicking the somatic evolution strategy of the immune system . However, other in vitro display systems, such as yeast display, have important advantages over the filamentous phage for affinity maturation , and regardless of the display method, selection of \"improved\" variants can be slow and cumbersome. Iterative methods have been developed to combine computationally designed mutations and circumvent the screening of combinatorial libraries, but these have had limited success to date. Title: A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris", "Passage: secretion to display for full length IgGs, they suffer drawbacks of their own, including the need for modifying the protein sequence to allow surface binding in particular cases. Moreover, re-capture following secretion introduces the risk of \"crosstalk\" between clones that could lead to the loss of the required genotype-to-phenotype relationship that is critical for efficient lead-cell isolation. Without a strong genotype-to-phenotype relationship built into the display system the issue of \"cross talk\" among clones in the same culture must be addressed through tedious experimental modifications . Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Nearly all applications of the filamentous phage depend on its ability to display polypeptides on the virion's surface as fusions to phage coat proteins . The display mode determines the maximum tolerated size of the fused polypeptide, its copy number on the phage, and potentially, the structure of the displayed polypeptide. Display may be achieved by fusing DNA encoding a polypeptide of interest directly to the gene encoding a coat protein within the phage genome , resulting in fully recombinant phage. Much more commonly, however, only one copy of the coat protein is modified in the presence of a second,", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The proportion of fatal MERS cases within the KSA compared to outside the KSA, as well as the age, and sex distribution change in different ways when comparing MERS outbreaks. Approximately 43 % of MERS cases in the KSA were fatal betwen 2012 and December 2015 while 21 % died among those occurring outside of the KSA. The total number of male cases always outnumber females and the proportion of male deaths is always greater than the proportion of females who die. However the proportion of male deaths from total males with MERS is a similar figure to that for Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: or worse, and secondary bacterial infections have been reported . Disease can progress to acute respiratory distress syndrome and multiorgan system failure . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported . General supportive care is key to managing severe cases . Children under Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: Among confirmed cases, only 25.2% were healthcare workers, whereas around 75% were non-healthcare workers. Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers .", "Title: Improving health aid for a better planet: The planning, monitoring and evaluation tool (PLANET)\nPassage: to maximize health outcomes. The outcome would be a comprehensive list with competing priorities ranked according to the combined scores they received in the process. Such a list would be helpful because it provides an overview of the strengths and weaknesses of competing DAH options against many criteria, based on the collective input of technical experts. The list can also be adjusted by taking the values of many stakeholders into account such as occurred during the extensive experience with the implementation of CHNRI in health research prioritization . Title: Setting healthcare priorities in hospitals: a review of empirical studies", "Passage: decisions and subsequent revisions of decisions in light of further arguments. The 'enforcement' criterion requires that some form of regulation exists to make sure that the first three conditions are met . While a focus on the fairness and legitimacy of priority setting processes is indisputably important, understanding what substantive principles are employed in priority setting and how they are operationalized SETTING HEALTHCARE PRIORITIES IN HOSPITALS in local context is equally important. For example, do hospitals allocate their resources across services according to severity of disease or efficiency? And how do they define and specify these principles? While this distinction Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: targeted investments guided by proper prioritization resulted in a 40% reduction in child mortality in test districts . Title: Setting healthcare priorities in hospitals: a review of empirical studies", "Passage: the four conditions of AFR such as relevance, publicity, appeals and revision and enforcement. The 'publicity' criterion holds that resource allocation decisions must be public, including the grounds for making them. The criteria for 'relevance' require that the basis on which allocative decisions are made must be ones that 'fair-minded people can agree are relevant to meeting the healthcare needs fairly under reasonable constraint' . Arguments should rest on scientific evidence, though not necessarily a specific kind of evidence . The 'revisions and appeals' process criterion requires that there is an institutional mechanism that provides for channels for appeals to", "Title: Estimating the number of infections and the impact of non-\nPassage: representing between 1.88% and 11.43% ofthe population. The proportion of the population infected Title: A Bayesian Inferential Approach to Quantify the Transmission Intensity of Disease Outbreak\nPassage: According to World Health Organization update of November 20, 2009 , virus spread across more than 206 countries resulting in 6770 deaths . In June 2009 World Health Organization raised the level of pandemic alert phase 5 to phase 6 . According to the Directorate General of Health Services, Government of India, New Delhi, update on November 19, 2009 , there have been 16044 laboratories confirming cases recorded in India resulting in 537 deaths . Title: Influenza, evolution, and the next pandemic", "Passage: The 1918 influenza pandemic is remembered because it killed as many as 50-100 million people worldwide: an estimated 2.5% or more of the global population . Remarkably, the mortality rate was much higher in younger adults than it was in children, giving rise to the familiar W-shaped pandemic mortality curve . A similar mortality pattern has not been described for subsequent pandemics . Title: Estimating the number of infections and the impact of non-\nPassage: Country % of total population infected", "Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk\nPassage: affect response to this opinion.", "Title: GI-16 lineage (624/I or Q1), there and back again: The history of one of the major threats for poultry farming of our era\nPassage: Understandably, other factors could have played a role, like within-country viral evolution leading to the emergence of virulent strain, more fit for the Italian context. To investigate this issue, an ancestral state reconstruction of the amino-acid profile variation over time was performed using a Maximum-likelihood approach . Albeit some amino-acid changes were detected in the clade including contemporary Italian strains, no distinctive mutations differentiating this group from their ancestors were identified, at least in the considered region. While the \"local evolution\" hypothesis appears lessened by this evidence, further studies will be necessary to investigate the potential role of other S1/genomic Title: Description of two measles outbreaks in the Lazio Region, Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection", "Passage: The D4 genotype, grouped in two different clusters of common origin, was responsible for the first cases reported in the Roma/Sinti population and detected in several other cases, including the Italian ethnic population, up to December 2006. Starting in October 2006 the B3 genotype was isolated in a contact of a case from the school outbreak, overlapping for some time with genotype D4 . Title: Lessons from the History of Quarantine, from Plague to Influenza A\nPassage: A rigid maritime cordon could only be effective in protecting small islands. During the terrifying cholera epidemic of 1835-1836, the island of Sardinia was the only Italian region to escape cholera, thanks to surveillance by armed men who had orders to prevent, by force, any ship that attempted to disembark persons or cargo on the coast . Title: Lessons from the History of Quarantine, from Plague to Influenza A\nPassage: isolation was improved .", "Title: CDC Summary 21 MAR 2020,\nPassage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: naturally occurring pattern following the evolutionary characteristics typical of CoVs, it is highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species are the most revealing signs that SARS-CoV-2 evolved by natural evolution. A search for an intermediate animal host between bats and humans is needed to identify animal CoVs more closely related to human SARS-CoV-2. There is speculation that pangolins might carry CoVs closely related to SARS-CoV-2, but the data to substantiate this is not yet published . Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: infections and 800 deaths, and Middle East respiratory syndrome CoV which has caused a persistent epidemic in the Arabian Peninsula since 2012 . In both of these epidemics, these viruses have likely originated from bats and then jumped into another amplification mammalian host for SARS-CoV and the dromedary camel for MERS-CoV] before crossing species barriers to infect humans. Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: The pathogenicity of these viruses is typically species-dependent, as is the severity of infection; they infect mainly their natural hosts and/or species that are closely related. Certain virus infections, however, can cross the species barrier, with the prime example being the zoonotic SARS-CoV, a novel coronavirus that is thought to have originated from bats before it adapted to its intermediate host, civet cats, and finally to humans . Bat colonies, which are scattered worldwide, are widely known to play host to a variety of coronaviral and adenoviral pathogens while acting as natural wildlife reservoirs of these viruses .", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: effects upon their bacterial hosts that may not result in the development of resistance to infection. Several studies have reported increased antibiotic sensitivity in bacterial populations simultaneously infected with either wild type filamentous phage or phage engineered to repress the cellular SOS response . Filamentous phage f1 infection inhibited early stage, but not mature, biofilm formation in E. coli . Thus, unmodified filamentous phage may be of future interest as elements of combination therapeutics against certain drug-resistant infections. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: effects upon their bacterial hosts that may not result in the development of resistance to infection. Several studies have reported increased antibiotic sensitivity in bacterial populations simultaneously infected with either wild type filamentous phage or phage engineered to repress the cellular SOS response . Filamentous phage f1 infection inhibited early stage, but not mature, biofilm formation in E. coli . Thus, unmodified filamentous phage may be of future interest as elements of combination therapeutics against certain drug-resistant infections. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: Despite this, the filamentous phage remains highly useful as a carrier for peptides with relatively simple secondary structures, which may be stablilized via anchoring to the coat proteins . This may be especially true of peptides with poor inherent immunogenicity, which may be increased by high-valency display and phage-associated adjuvanticity . Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: Despite this, the filamentous phage remains highly useful as a carrier for peptides with relatively simple secondary structures, which may be stablilized via anchoring to the coat proteins . This may be especially true of peptides with poor inherent immunogenicity, which may be increased by high-valency display and phage-associated adjuvanticity .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: AAV vector systems have a number of engaging properties. The wild type viruses are non-pathogenic and replication incompetent in humans and the recombinant AAV vector systems are even further attenuated . As members of the parvovirus family, AAVs are small non-enveloped viruses that are stable and amenable to long-term storage without a cold chain. While there is limited preexisting immunity, availability of non-human strains as vaccine candidates eliminates these concerns. Modifications to the vector have increased immunogenicity, as well . Title: Viral vector-based influenza vaccines", "Passage: Adeno-associated virus is a parvovirus that is replication-deficient in humans. Like adenovirus, AAV has a broad cell, tissue and host tropism and therefore is a potential good vector vaccine. 218 However, drawbacks of using AAV include: limited capacity for transgenes, presence of pre-existing immunity in humans and the technical challenge of producing high titer stocks. Initially, AAV was not explored as a vaccine vector as it was considered to be poorly immunogenic, however vaccination studies in mice showed that AAV-2 expressing an HSV-2 glycoprotein was immunogenic and a potent inducer of Tcell and antibody responses, 219 and currently modifications are Title: Viral vector-based influenza vaccines", "Passage: being made to AAV to increase immunogenicity. 220 A limited number of studies evaluating AAV as a vector for influenza vaccination has been performed . Initially, an AAV expressing the HA gene or NP gene was shown to be protective in mice. 221, 222 A more recent study tested AAV vaccines expressing the HA, NP or M1 genes of H1N1pdm09 in mice. Whereas AAV-HA afforded full protection from H1N1pdm09 infection, AAV-NP protected mice partially and AAV-M1 did not afford protection. Simultaneous vaccination with all 3 constructs afforded protection from homologous challenge infection. 223 Recently, in an alternative vaccination approach, AAV Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Adeno-associated viruses were first explored as gene therapy vectors. Like rAd vectors, rAAV have broad tropism infecting a variety of hosts, tissues, and proliferating and non-proliferating cell types . AAVs had been generally not considered as vaccine vectors because they were widely considered to be poorly immunogenic. A seminal study using AAV-2 to express a HSV-2 glycoprotein showed this virus vaccine vector effectively induced potent CD8 + T cell and serum antibody responses, thereby opening the door to other rAAV vaccine-associated studies .", "Title: The role of viral persistence in flavivirus biology\nPassage: brane , and envelope , and seven nonstructural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 . The defined functions of these proteins are presented in Table 1 . However, the precise function of some of the proteins remains to be elucidated. Furthermore, it should be noted that the bulk of the studies have been carried out in MBFV systems, and it is possible that the functions may not be identical in TBFV. Title: Advances in Zika Virus\u2013Host Cell Interaction: Current Knowledge and Future Perspectives", "Passage: Nonstructural proteins have roles during the virus life cycle and directly interact with signaling proteins of the innate immune response. Sironi et al. has emphasized the selective pressures faced by NS1 in flaviviruses and its important functions in viral RNA replication and immune evasion, as seen during the pathogenesis of DENV . The amino acid differences in NS1 proteins may explain the difference between the virus-host interaction of flaviviruses, and how the host immune response is differentially modulated to viruses such as ZIKV in comparison to DENV. Furthermore, by interacting with host immune components like the RIG-I-like receptors, NS1 proteins Title: Viral Interference and Persistence in Mosquito-Borne Flaviviruses", "Passage: However, the interaction between the ribosomal proteins S6 and L4 and the NS2A and NS4B nonstructural viral proteins is likely involved in flavivirus RNA translation . This report provided the first evidence of the binding of flaviviral proteins to either 40S or 60S ribosomal proteins. However, this interaction has been reported in other viruses, such as Epstein-Barr virus noncoding RNA EBER1, which recruits ribosomal protein L22 during infection, presumably, to aid in viral replication, or the hepatitis C IRES region, which associates with the ribosomal S5 protein to position the HCV RNA on the 40S ribosomal subunit during translation . Title: The role of viral persistence in flavivirus biology", "Passage: DIII is associated with receptor binding and is also a target for several neutralizing monoclonal antibodies. Crystal structures of the E protein from several flaviviruses all show similar secondary structure and domain organization . The E protein is important in determining neuroinvasiveness and neurovirulence for several MBFVs . For WNV, JEV, and DENV, mutations in the E protein affect fusion and receptor binding with target cells The E protein was first described in 1995 and later has been extensively defined and crystalized for many other flaviviruses . TBFV E protein is important for determining neurovirulence and neuroinvasiveness Nonstructural Proteins NS1", "Title: Techniques to Study Antigen-Specific B Cell Responses\nPassage: In his Nobel lecture in 1908, Paul Ehrlich likened the antibody-antigen interaction to a lock and key. He reasoned that antitoxins contained in a solution in the serum of immunized animals must be identical to a cellular receptor \"for a really well-made key will not open different locks at the same time\" . It took almost five decades before immunofluorescence microscopy was used to confirm the cellular origin of antibodies . Major strides in the B cell and antibody field followed in the 1970s with the development of hybridoma technology to produce monoclonal antibodies and the discovery that somatic rearrangement Title: Antibody Engineering for Pursuing a Healthier Future", "Passage: Monoclonal antibodies are clinically significant homogeneous and mono-specific scientific biomolecules produced from hybridoma cells by hybridoma technology . mAbs arise from single cell clone compared to multiple cell clones for pAbs . Since their discovery, these molecules have been used as research tools and have revolutionized the fields of biotechnology, immunology, diagnostics, and medicine. The technology was described for the first time by K\u00f6hler and Milstein in the mid-1970s in the journal Nature, and they were later awarded the Nobel Prize . Title: Techniques to Study Antigen-Specific B Cell Responses", "Passage: Text: In his Nobel lecture in 1908, Paul Ehrlich likened the antibody-antigen interaction to a lock and key. He reasoned that antitoxins contained in a solution in the serum of immunized animals must be identical to a cellular receptor \"for a really well-made key will not open different locks at the same time\" . It took almost five decades before immunofluorescence microscopy was used to confirm the cellular origin of antibodies . Major strides in the B cell and antibody field followed in the 1970s with the development of hybridoma technology to produce monoclonal antibodies and the discovery that somatic Title: mRNA as novel technology for passive immunotherapy", "Passage: In 1975, groundbreaking work described the production of monoclonal antibodies by immortalization of B cells . The resulting hybridoma technology was then rapidly exploited for clinical use, for instance, to produce a mAb to CD3 for preventing organ rejection . Recombinant technologies further expanded the available therapies based on mAbs. In vitro antibody selection technologies like phage or ribosome display were developed to enable the generation of highly specific human mAbs out of libraries that may even be na\u00efve for the specific antigens 1 Schematic illustration comparing active immunization and passive antibody immunotherapies. a During active immunization triggered by natural", "Title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: Hantaan virus is an enveloped, negative-sense RNA virus from the genus Hantavirus within the family Bunyaviridae. It causes HFRS, which is an important threat to public health worldwide. It is also a potential weapon for biological terrorism. Reservoir animals, usually rodents, are asymptomatic during persistent infection. Unlike in rodents, Hantavirus infection leads to HFRS and Hantavirus pulmonary syndrome in humans . The major clinical characteristics of HFRS include fever, hemorrhage, hypotension, and renal injury , causing severe manifestations and death in some cases. The current standard of care for HFRS relies on symptomatic and supportive treatment. It has been confirmed Title: Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/K(b) Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: To ensure the sample size in some statistical analyses, we combined the patients according to the disease severity into mild/moderate and severe/critical groups for comparison. In this case, the number of patients with a severity degree of mild/moderate and severe/critical was 22 and 23, respectively. According to the clinical observation, the illness could be divided into the acute phase and the convalescent phase . Title: Quantification of Hantaan Virus with a SYBR Green \u2160-Based One-Step qRT-PCR Assay", "Passage: Hantaan virus is a worldwide pathogen that causes serious infectious disease featured with febrile, mucocutaneous hemorrhage, renal damage and shock. The disease is thus named hemorrhagic fever with renal syndrome . The cases of HFRS in China account for nearly 90% of all HFRS cases worldwide . During 1950-2007, 1,557,622 HFRS cases and 46,427 deaths from HFRS were reported in China , and HFRS cases are reported in most provinces and cities of mainland China annually , making HFRS a notable public health problem. Shaanxi province, which is located in northwest of China, is one of the most seriously afflicted Title: Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/K(b) Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome\nPassage: HTNV infection in humans.", "Title: DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles\nPassage: The only definitive method for successfully identifying vaccinated animals in the presence of an active viral infection is to determine the rate of viral shedding by virus isolation, cytokine/interleukin profiling or virus neutralization assay . These types of analysis require repeated sampling, a period for seroconversion and are expensive compared to serology based ELISA, and are therefore not routinely employed during endemic viral infection outbreaks. Differentiating infected from vaccinated animals marker vaccines can be employed to differentiate vaccine antibody responses from that of wild type virus. Companion serology based tests rely on seroconversion, and upon exposure to wild type virus Title: Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients", "Passage: This first comprehensive study addresses important issues of the identification of markers for severity of p-H1N1-09 infection and dynamics of immune responses in severe disease by evaluating several parameters. The investigations were initiated during the early phase of the pandemic when isolation of all the Figure 3 . Gene expression analysis. Gene expression profiles of total PBMCs from blood samples of mild and critically ill cases and lung aspirate cells from critically ill cases were determined using TaqMan Low Density immune panel arrays. PBMCs from six healthy individuals were taken as controls, which were treated as replicate arrays to calculate Title: Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy", "Passage: Immunologists developed various approaches to study the dynamics of immune cells at different stages of the immune response under physiological conditions in vivo. MP-IVM has also been applied to visualize the immune response to viral infections in different organs . Adoptive transfer of fluorescent immune cells and the use of reporter viruses allowed the temporal and spatial analysis of a local immune response during infection with different viruses such as herpes simplex virus, vaccinia virus and vesicular stomatitis virus . Although viral pathogens were used, the focus of these studies was on immune cells and the dynamics of their response. Title: Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients", "Passage: followed by FACS analysis. Scatter dot plots and histograms: A representative sample each from different categories, a) healthy individual, b) mild case, c) critically ill case, d) TLR levels: Expressed as median fluorescence intensities for different categories of patients. doi:10.1371/journal.pone.0013099.g002 downregulation of most of the immune function genes. Cluster 2 contained all sequential samples from the seasonal flu case and one pH1N1 case . Though most of the gene expression levels were similar to survived case, S7 did not survive. Genes formed four clusters, A, B, C and D. Cluster C contained majority of the analyzed genes and all were", "Title: Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study", "Passage: Whilst all HCWs agreed colleagues habitually reported symptoms informally when notifying their absence, a number of benefits of frequent monitoring were highlighted such as the ability to 1.) identify staff absenteeism, 2.) improve infection control monitoring, and 3.) prevent spread of infections resulting in reduced rates of illness. Willingness to disclose symptoms for routine surveillance however varied. UK participants were more open towards discussing symptoms and were of the view their colleagues would also be, in cases where the sickness was genuine and the rationale of the reporting system understood . They were nevertheless also concerned that detailed enquiries could Title: Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study", "Passage: There is evidence to support HCWs' fears of the increased risk in accident and emergency and intensive care departments as studies had found H1N1 attack rates among staff highest in these departments . Concepts for a surveillance system in this population could focus primarily in these departments where HCWs may have a higher invested interest. However, even during a pandemic, at varying World Health Organisation levels of alerts, it was difficult to motivate HCWs to take precautionary measures . Title: Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study", "Passage: Thirdly, all participants discussed the current role of occupational health departments and opportunities for their involvement in a surveillance system of this kind. Participants criticised the lack of funding and resources supplied to these departments, which currently played a minor role in managing HCWs' health beyond initial employment screening. They felt occupational health departments would be well placed to manage symptom and personal health data and organise diagnostic testing, and were keen to see their function broaden, assisting with the management of acutely as well as chronically sick staff, and in particular those symptomatic in the work place. Further, they Title: Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study", "Passage: Asking HCWs to report symptoms when absent from work with a suspected contagious illness may be feasible as a means of surveillance for EIDs in some settings. However, more fundamental issues need to be addressed for the further development of this concept. These include standardising a culture of safe healthcare with education and compliance in infection control, tackling staffing pressures, homogenising absence recording, reviewing sick pay entitlements and improving the understanding of nosocomial outbreaks. Pilot studies will need to be tailored to specific countries and hospitals to investigate how these initial concepts may be adapted.", "Title: Host resilience to emerging coronaviruses\nPassage: REviEW Jamieson future science group Risk factors for SARS-CoV patients included an older age and male . Immune factors that increased mortality for SARS-CoV were a higher neutrophil count and low T-cell counts . One factor that increased disease for patients infected with SARS-CoV and MERS-CoV was infection with other viruses or bacteria . This is similar to what is seen with many other respiratory infections. A recent study looking at malaria infections in animal models and human patients demonstrated that resilient hosts can be predicted . Clinical studies have started to correlate specific biomarkers with disease outcomes in ARDS Title: Host resilience to emerging coronaviruses", "Passage: higher mortality rate, with 35-50% of diagnosed infections resulting in death . These deadly betacoronavirus viruses existed in animal reservoirs 9, . Recently, other CoVs have been detected in animal populations raising the possibility that we will see a repeat of these types of outbreaks in the near future . Both these zoonotic viruses cause a much more severe disease than what is typically seen for CoVs, making them a global health concern. Both SARS-CoV and MERS-CoV result in severe lung pathology. Many infected patients have acute lung injury , a condition that is diagnosed based on the presence of Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: In the winter season there comes the time of upper and lower respiratory tract infections characterised by cough, dyspnea and eventually fever .Some of the patients, especially older people living alone affected by the disease ,may need hospitalization and eventually intensive care. In many of the cases who are hospitalized nasal and/or tracheal fluid are examined for viral or bacterial agents. Only in less than 50% of the cases influenza viruses are considered to be the cause of the disease.In the rest of the cases diagnostic procedure for human coronaviruses is not performed routinely. One of the fourdifferent Human Coronaviruses Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: cases of human infection, with a fatality rate of 9.6%, were reported to the World Health Organization from November 2002 to July 2003. High levels of proinflammatory cytokines, including tumor necrosis factor -\u03b1, interleukin -1\u03b2, and IL-6, were detected in autopsy tissues from SARS patients . Although dysregulation of inflammatory cytokines may be involved in lung injury and the pathogenesis of SARS-CoV, the underlying molecular mechanisms are not fully understood.", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: Symptoms at the point of diagnosis were reported for 31 cases. Two cases were asymptomatic and remained so until tested negative. The asymptomatic cases were tested as part of screening following repatriation and during contact tracing respectively. Of the remaining 29, 20 reported fever, 14 reported cough and eight reported weakness. Additional symptoms reported included headaches , sore throat , rhinorrhoea , shortness of breath , myalgia , diarrhoea and nausea . Fever was reported as the sole symptom for nine cases. In 16 of 29 symptomatic cases, the symptoms at diagnosis were consistent with the case definition for acute Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "Passage: The 2019-nCoV infected cases have symptoms like fever, fatigue, dry cough, dyspnea etc., with or without nasal congestion, runny nose or other upper respiratory symptoms . Despite the atypical symptoms were reported , Nan-Shan Zhong, the academician of Chinese Academy of Engineering in an exclusive interview with Xinhua News Agency on 28 January 2020, pointed out that fever is still the typical symptom of 2019-nCoV infection. Title: CDC Summary 21 MAR 2020,", "Passage: People who get a fever or cough should consider whether they might have COVID-19, depending on where they live, their travel history or other exposures. More than half of the U.S. is seeing some level of community spread of COVID-19. Testing for COVID-19 may be accessed through medical providers or public health departments, but there is no treatment for this virus. Most people have mild illness and are able to recover at home without medical care. Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "Passage: Coronavirus 2019-nCoV infection commonly presents with signs and symptoms of pneumonia or as a nonspecific lower respiratory illness, with coughing or difficulty breathing accompanied by fever. 5, 19, 20 Fever and cough constitute the most common presentations. However, patients may have other respiratory symptoms, sore throat, nasal congestion, malaise, myalgia, and headache. Bilateral infiltrates may be seen on chest X-ray. Severe cases may present with sepsis and even shock. Conversely, some patients may present as only mildly ill or asymptomatic altogether. 21 To date, patients with underlying medical conditions and the elderly are more likely to become severely ill, require", "Title: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data\nPassage: Given the noisy data and the lack of disease transmission mechanism, our search for the best fitting model might have led to over-fitting. The selection and aggregation of predictors, therefore, is guided by both practical knowledge and model performance comparison, in order to achieve a balanced model version that is of relatively good fit and meaningful for practitioners to interpret. For instance, the predictors are grouped in a relatively arbitrary manner, but the selection process for the pandemic model was blinded from the results of posteriors for each parameter before the final model version was selected. Title: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data", "Passage: For pandemic period, a model is constructed based on the hypothesis that, the values reported by each surveillance system reflect both actual disease status and public awareness. The information environment input can influence the level of actual disease trends being captured through a multiplier \u03b8 j,t , and the level of public awareness imbedded in the surveillance systems \u03c6 j,t for each surveillance system j at time t. Title: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data", "Passage: pandemic influenza terms. Figure 5 Posterior distributions of \u03b1 j,t,m in \"excess\" parameter \u03c6 j,t as measure of correspondence between surveillance and the information environment proxy data during the pandemic period. \u03b12 is the coefficient for total number of alerts at HealthMap; \u03b13 is the coefficient for the total number of unique alerts at HealthMap; \u03b14 is the coefficient for number of healthcare facilities related alerts at HealthMap; \u03b15 is the coefficient for %RSV from virological surveillance; \u03b16 is the coefficient for Google search index of authority; \u03b17 is the coefficient for Google search index of pandemic influenza terms. Title: Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study", "Passage: We analyzed if the phylogenetic summaries divergence, diversity, lineages and TMRCA have any effect on estimates of the epidemiological parameters of SEIRS model. To this end, we fitted the first tier of the SEIRS model to the epidemiological summaries \u00b5-attack, \u03c3-attack, correlation, explosiveness and pop-attack in Table 1 , using the same prior densities as in Table 2 .", "Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam\nPassage: The results presented here highlight three main findings: 1) when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor; but in peri-urban landscapes emergence factors converge, including higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture; 2) high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks; as are 3) landscapes where intensive and extensive forms of poultry production are co-located. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: The results presented here highlight three main findings: 1) when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor; but in peri-urban landscapes emergence factors converge, including higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture; 2) high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks; as are 3) landscapes where intensive and extensive forms of poultry production are co-located. Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model\u2019s predictability. Similarly, landscapes where Title: Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam", "Passage: and space of processes associated with land-cover and land-use changes. Project results question whether the urban/rural land-use dichotomy is useful when large areas and parts of the population are caught between the two. Planners need better tools for mapping the rural-urban transition, and for understanding how the specific nature of peri-urban environments creates elevated health risk that require adaptation of existing planning, land use, and development practices.", "Title: SMS-based smartphone application for disease surveillance has doubled completeness and timeliness in a limited-resource setting \u2013 evaluation of a 15-week pilot program in Central African Republic (CAR)\nPassage: the focal points show little variability and the app were ranked highly on all dimensions. It is possible that the instrument used was not adequately sensitive and/or that participants chose to provide a positively biased evaluation of the app to the investigators. Title: Complement in Action: An Analysis of Patent Trends from 1976 Through 2011", "Passage: inhibit the cleavage of C5 to C5a and C5b have been used to treat arthritis and prevent excessive downstream complement activation . A C3 precursor biopolymer detected through the use of mass spectrometry has been utilized as a biomarker for type II diabetes . Finally, the levels of C4d and/or C3d on the surface of T lymphocytes, B lymphocytes, or monocytes in blood samples have been used to diagnose SLE . These are just a few examples of the many disease-related applications of complement that have been patented in the USA, yet they impressively illustrate the large diversity and creativity Title: SMS-based smartphone application for disease surveillance has doubled completeness and timeliness in a limited-resource setting \u2013 evaluation of a 15-week pilot program in Central African Republic (CAR)", "Passage: Generalization of these results to a setting of more active conflict and greater insecurity should be done cautiously. Finally, it is recognized that sustainability of this pilot initiative and its scale-up to a national level are challenging and will require long-term political commitment, training and resources. Title: SMS-based smartphone application for disease surveillance has doubled completeness and timeliness in a limited-resource setting \u2013 evaluation of a 15-week pilot program in Central African Republic (CAR)", "Passage: data transmission between health facilities and district offices in a number of low-income countries, including several in sub-Saharan Africa . Apps have the potential to improve surveillance and to hasten control of potential epidemics. To our knowledge, apps have been used to collect and transmit data on a limited number of diseases or in an emergency context but not on a large portfolio of health conditions in a context of post-conflict insecurity. This report describes the implementation and evaluation of an app surveillance system for the notification of Alerts and transmission of Weekly Reports on 20 conditions from 21 health", "Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study\nPassage: The primary objective of this study was to provide health authorities with evidence-based practical information to guide the development and delivery of key health messages for H1N1 and other health campaigns. The study focused on community responses to key health messages in the 2009 and 2010 H1N1 campaigns. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: The general objective of this work is to utilize radio frequency close-proximity sensors to describe and understand the nature of human networks within a low-resource population that have the potential to transmit respiratory infectious diseases. Specifically: Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: The overall objective of the study was to quantify the efficacy of face masks and/or hand hygiene in reducing transmission of influenza to household contacts at the individual level. Specific objectives of this pilot study were to confirm the feasibility of the study design including the practicability of patient recruitment, randomization and follow-up, the appropriateness of the estimated sample size for a subsequent larger trial in terms of characteristics of local circulating influenza viruses and potential effect sizes, the applicability of the interventions and individual adherence with the interventions. Title: Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study", "Passage: Confirmatory factor analysis, CFA, with AMOS 16 was employed to test the hypothesized measurement model with respect to intention, attitudes, subjective norms and moral norms, specifying the relationship between the observed variables and the underlying latent variables . Thus CFA was used to test whether the Tanzanian and Sudanese data were consistent with an a priori hypothesized 4-factor model. The parameters of the model were estimated with maximum likelihood estimation. Missing data were assumed to be missing at random and was handled using the direct approach in AMOS 16 .", "Title: Insights into the transmission of respiratory infectious diseases through empirical human contact networks\nPassage: describes the duration of the disease spread. Title: The role of heterogeneity in contact timing and duration in network models of influenza spread in schools\nPassage: We assumed that symptom onset of infected individuals occurred later than shedding onset. Specifically, infected individuals entered a symptomatic state after a random, log-normally distributed incubation period with a mean of 1.52 days and a standard deviation of 0.66 . We correlated the latent and incubation period distributions, such that shedding began 0.5-1.2 days before symptom onset. However, under our assumptions for timevarying infectiousness, shedding amounts did not increase to an appreciable level until closer to the time of symptom onset. Title: The Waiting Time for Inter-Country Spread of Pandemic Influenza", "Passage: infected travelers is in delaying a local epidemic we need better knowledge about the infectiousness of individuals before and just after the onset of symptoms. It is assumed that the pandemic is identified and declared when there are 10 concurrent cases in the source region attributed to human-to-human transmission, and that screening is applied at both departure and arrival. The time between screening events is assumed to be 12 hours and infected travelers are not isolated following the onset of symptoms. Of the border control measures available, reducing traveler numbers has the biggest effect on the delay and even then Title: Introducing the Outbreak Threshold in Epidemiology\nPassage: as the fact that the incubation period is around 5 days, by which point it had easily caused more secondary cases. However, in subsequent outbreaks super-spreaders might not be infected early on, allowing more time to contain the spread.", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: virus is usually described by the media as 'deadly' and although this is true in the sense that it has caused deaths, the nuances of uncertain case fatality rates in the early stages of an outbreak are not being communicated. The current estimated case fatality rate seems to be around 3% which is significant but not comparable to the 10% rate for SARS or 34% reported for MERS. These misperceptions are still driving public anxiety. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: Similarly, MERS-CoV appears to have high severity and low transmissibility. Since 2012, MERS-CoV has caused 2494 reported cases and 858 deaths in 27 countries. MERS-CoV has also caused some rapid outbreaks, mainly in hospitals in Saudi Arabia, Jordan, and South Korea, but estimates of MERS-CoV R0 are less than 1, and thus far it has been contained.5 Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory\nPassage: is is in agreement with the study done by Ahmad to estimate the survival rate in MERS-CoV globally prior to 26 January 2017; 86.9% were not health-care workers compared with 13.1% confirmed cases of healthcare workers . Similarly, other studies also reported a lower prevalence in healthcare workers . Title: Clinical review: Mass casualty triage \u2013 pandemic influenza and critical care", "Passage: and case fatality rates during a pandemic, including the potential for more than one wave. The base scenario assumes a clinical attack rate of 25% and a case fatality rate of 0.37%, giving rise to 53,700 excess deaths in the UK. A reasonable worst case scenario involves a cumulative clinical attack rate of 50% with 2.5% case fatality, causing 709,300 excess deaths. Similarly, the US Department of Health and Human Services predicts that in a \"moderate\" scenario based on a virus with 1968-like pathogenicity, 865,000 will require hospitalisation and 65,000 will require ventilation. They also outline a \"severe\" 1918-like scenario", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: A role for T cell-mediated pathological responses in HFRS and HCPS has been the source of speculation for a variety of reasons. The severity of SNV-associated HCPS may have made it more apparent that the onset of pulmonary edema, tachycardia and hypertension seemed to be all but universally temporally associated with the appearance of a spectrum of highly-activated cells of the lymphoid lineage in the peripheral blood. Cells with a close morphologic similarity to these -immunoblasts\u2016 were detected in the congested, heavy lungs of patients who came to autopsy, as well as in lymphoid organs and in the portal triads Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: severe forms of HFRS and HCPS have begun to achieve sufficient mass as to induce, through PAMP-PRR interactions and other means, the expression of proinflammatory cytokines . For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed, and yet it is often not appreciated that the expected preferential tissue tropism of HFRS-associated viruses and their HCPS-associated counterparts for the renal and pulmonary beds, respectively, is not as one would predict through the manifestations of the two diseases. Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Local elaboration of inflammatory and chemotactic mediators is considered to be a requirement for the development of systemic disease symptoms, with those abnormalities sometimes culminating in shock and death. Yet it is not hypoxemia, due to the prominent pulmonary edema, that leads to death in most fatal cases of HCPS, but rather intoxication of the heart by as-yet-undefined mediators that leads to the low cardiac output state and the associated shock syndrome . It is tempting to speculate that mediators produced in the lung in connection with the inflammatory infiltrate can percolate through the coronary circulation with minimal dilution in Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Hantavirus infections became a concern in the Americas after the description of an outbreak of acute respiratory distress occurred in the Four Corners area in 1993 . The newly recognized disease, hantavirus cardiopulmonary syndrome, HCPS , was linked to infection by the newly-discovered Sin Nombre virus , and the rodent Peromyscus maniculatus was identified as the reservoir . However, hantavirus infections have a much longer history. A review of ancient Chinese writings, dating back to approximately 960 AD, revealed descriptions closely resembling hemorrhagic fever with renal syndrome , the syndrome caused by Old World hantaviruses . During the twentieth century,", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The NYVAC vector is a highly attenuated vaccinia virus strain. NYVAC is replication-restricted; however, it grows in chick embryo fibroblasts and Vero cells enabling vaccine-scale production. In non-permissive cells, critical late structural proteins are not produced stopping replication at the immature virion stage . NYVAC is very attenuated and considered safe for use in humans of all ages; however, it predominantly induces a CD4 + T cell response which is different compared to MVA . Both MVA and NYVAC provoke robust humoral responses, and can be delivered mucosally to induce mucosal antibody responses . There has been only limited exploration Title: Virus-Vectored Influenza Virus Vaccines", "Passage: . Intriguingly, NYVAC may have an advantage for use as an influenza vaccine vector, because immunization with this vector induces weaker vaccine-specific immune responses compared to other poxvirus vaccines, a feature that may address the concerns surrounding preexisting immunity . Title: Efficient Production of Human Norovirus-Specific IgY in Egg Yolks by Vaccination of Hens with a Recombinant Vesicular Stomatitis Virus Expressing VP1 Protein", "Passage: The animal study was conducted in strict accordance with USDA regulations and the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and was approved by The Ohio State University Institutional Animal Care and Use Committee . Chickens were housed in cages inside high-security isolation rooms provided with HEPA-filtered intake and exhaust air at The Ohio Agriculture Research and Development Center, The Ohio State University. The animal care facilities at The Ohio State University are AAALAC accredited. Before animal study, blood samples were collected from each chicken to confirm that they Title: Efficient Production of Human Norovirus-Specific IgY in Egg Yolks by Vaccination of Hens with a Recombinant Vesicular Stomatitis Virus Expressing VP1 Protein", "Passage: Purification of VLPs from insect cells was described previously with some minor modifications . Spodoptera frugiperda cells were infected with baculovirus expressing HuNoV VP1 at an MOI of 10, and the infected Sf9 cells and cell culture supernatants were harvested at 6 days postinoculation. The VLPs were purified from cell culture supernatants and cell lysates by ultracentrifugation through a 40% sucrose cushion, followed by CsCl isopycnic gradient ultracentrifugation. Purified VLPs were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Coomassie blue staining. The protein concentrations of the VLPs were measured by using the Bradford reagent .", "Title: In Vitro Bactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA\nPassage: The antibiotic resistance of invasive pathogens has become one of the most challenging and persistent health problems . Methicillin-resistant Staphylococcus aureus has become the most common clinically relevant multiresistant pathogen causing both healthcare-associated and community-acquired bloodstream infections with mortality rates up to 40% . Title: In Vitro Bactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA", "Passage: The treatment failure of vancomycin, the therapeutic anti-MRSA agent of choice, due to the strains with elevated vancomycin minimum inhibitory concentration values within the susceptible range was described previously . Thus, the emergence of MRSA ) makes the discovery of new molecular scaffolds a priority, and the current situation even necessitates the reengineering and repositioning of some old drug families to achieve adequate control of these bacteria . However, for the treatment of S. aureus bloodstream infections, bactericidal antimicrobial agents are considered to be superior to bacteriostatic drugs . This fact should be considered during the development of effective and Title: In Vitro Bactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA", "Passage: The treatment failure of vancomycin, the therapeutic anti-MRSA agent of choice, due to the strains with elevated vancomycin minimum inhibitory concentration values within the susceptible range was described previously . Thus, the emergence of MRSA ) makes the discovery of new molecular scaffolds a priority, and the current situation even necessitates the reengineering and repositioning of some old drug families to achieve adequate control of these bacteria . However, for the treatment of S. aureus bloodstream infections, bactericidal antimicrobial agents are considered to be superior to bacteriostatic drugs . This fact should be considered during the development of effective and Title: In Vitro Bactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA", "Passage: Text: The antibiotic resistance of invasive pathogens has become one of the most challenging and persistent health problems . Methicillin-resistant Staphylococcus aureus has become the most common clinically relevant multiresistant pathogen causing both healthcare-associated and community-acquired bloodstream infections with mortality rates up to 40% .", "Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management\nPassage: As of July 2014, the number of confirmed cases of MERS-CoV has exceeded 830, with at least 288 associated deaths. 62 The majority of cases have involved patients with comorbidities and are predominately males with a median age of 47. 63, 64 Fewer than 25% of patients have reported contact with animals including dromedary camels, which have been shown to be one likely animal reservoir based on sero-positivity and detection of MERS-CoV. 65 More than 25% of the infections have been in healthcare workers, and the large number of nosocomial infections is likely due to inadequate infection control in hospitals Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: a case definition released by the KSA Ministry of Health in June 2015 . The KSA has been the source of 79 % of human cases. Severe MERS is notable for its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions . Interestingly in June 2015, an outbreak in South Korea followed a similar distribution . Among laboratory confirmed cases, fever, cough and upper respiratory tract signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia . Patients often present to a hospital with pneumonia, Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: or worse, and secondary bacterial infections have been reported . Disease can progress to acute respiratory distress syndrome and multiorgan system failure . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported . General supportive care is key to managing severe cases . Children under Title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory", "Passage: e literature shows that MERS-CoV infects males more than females . e casefatality rate of men is higher than that of women . Males with a history of serious medical conditions are highly susceptible to this infection. Moreover, the mean age of infection in adults is 60 years . e mode of transmission is not entirely understood yet ; however, human-to-human and zoonotic sources of transmission have been documented in many studies. Dromedary camels are the major animal source of MERS-CoV transmission to humans. Interhuman transmission of the virus did not occur easily, but it is seen mainly in patients'", "Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC\nPassage: RV infection triggers the release of a variety of antiviral factors and cytokines, including bradykinin, IL-1\u03b2, TNF\u03b1, IL-6 and IL-8, activating and attracting granulocytes, dendritic cells, and monocytes at the site of infection . An antibody response to RV infection also occurs with the development of serotype-specific neutralizing serum antibodies and secretory antibodies in the airways, detectable usually after one or two weeks after inoculation and maintained for at least one year . As RV infections are generally short-lived, these neutralizing antibodies appear after viral clearance, but have an essential role in protecting from reinfection from the same type of Title: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC", "Passage: directly impact virus-host interaction and weakens the innate immune response to infection. Testing other RV strains, but also other respiratory viruses, could bring a better understanding of this function and perhaps allow a generalization of this immune mechanism in the host antiviral response. A limitation of this study is the use of a mouse model system and mouse-adapted virus and it would be interesting to confirm these results in a human model, such as a three-dimensional human airway epithelia reconstituted in vitro . Title: Overview of the 3rd isirv-Antiviral Group Conference \u2013 advances in clinical management", "Passage: Human rhinoviruses usually cause mild acute respiratory infections, but on occasions can also cause more severe respiratory infections, including exacerbations of asthma and COPD. Of 115 Japanese children with asthma, a respiratory virus was detected in 86%, of which HRV or RSV were most common. 79 Ex vivo bronchial epithelial cells from people with asthma are more susceptible to HRV infection, due to deficient induction of IFN-b and IFN-lambda. In a study of 147 asthmatics on inhaled corticosteroid therapy, with a history of virusassociated exacerbations, patients were randomised to 14-day treatment with inhaled IFN-b or placebo within 24 hours of Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Symptoms are common to each infection and manifest on a gradient. Generally, but far from always, influenza infection is more likely to result in a patient feeling so unwell as to take to their bed and have a fever, than RSV, an HRV, CoV or other common cold virus infection, during which daily life is usually less impacted.", "Title: What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data\nPassage: Authority. The public healthcare sector currently accounts for over 90% of total secondary and tertiary care, while its subsidy from the Government has reached 95%. The public only needs to pay HK$100 per day to receive inpatient services, while the average operating cost is about HK$3,000 a day. Healthcare expenditure has been increasing, accounting for 25% of Government expenditures. With an ageing population of more than 13% aged 65 or over and an estimated increase to 28% by 2039, the whole sustainability of the public health system has been called into question and the Government has been actively trying to Title: What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data", "Passage: Mexico and United States but had a similar range like in Australia , Denmark , and Norway . However, does the significant drop of duration of stay in hospitals imply an improvement in health care services over time? A good quality of care is as essential as the efficiency of the health care system. Shortening in-hospital length of stay may be consistent with an orderly and systematic care pathway, but a longer length of stay might be regarded as appropriate for extended treatment. \"The problematic nature of relationship between length of stay and quality needs to be acknowledged.\" Our results Title: What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data", "Passage: Because disease patterns differ for each age group, age differences in reduction of hospitalization should also be considered. Hospitalization costs are a major component of healthcare expenditures in Hong Kong with a 7.0 million population. Healthcare expenditure has been increasing, accounting for 25% of Government expenditures which is relatively higher in comparing to other countries. About 80% of inpatients come from public hospitals under the Hospital Authority. The public healthcare sector currently accounts for over 90% of total secondary and tertiary care, while its subsidy from the Government has reached 95%. The public pays HK$100 per day to receive inpatient Title: What makes the hospitalisation system more efficient? An application of the decomposition method to Hong Kong morbidity data", "Passage: Also, the patient satisfaction However, the workload for the medical and health staff due to the shorter stays has not been properly measured and reflected in cost considerations. For example, arranging for day surgery, rather than admitting the patient overnight, implies that medical and health workers would have less time to do the preparation and provide the necessary services for operation. A recent survey in Hong Kong public hospitals indicated a very high burnt-out rate and increasing workload was one major factor. These are important elements and are consistently neglected in assessing the \"cost-effectiveness\" of shorter stays in the", "Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses\nPassage: The identical antibodies used in the ELISA-array format were also tested in a conventional ELISA format to determine the difference in sensitivity and specificity of the two methods. The conventional ELISAs were performed at the same time as the ELISA-array assays to ensure similar reaction conditions. The conventional ELISAs were performed in an identical maner to the ELISA-array, except that antibodies were coated at a concentration of 2 \u03bcg/mL in PBS , and substrate TMB was used instead of Super Signal ELISA Femto Maximum sensitive substrate . Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: ELISA-array. The ELISA-array assay is based on a \"sandwich\" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use. Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: The production of a reliable antibody chip for identification of microorganisms requires careful screening of capture of antibodies . Cross-reactivity must be minimized and the affinity of the antibody is as important as the specificity. First, we prepared and screened 23 monoclonal antibodies against eight viruses and verified the specificity and affinity to the target viruses by an immunofluorescence assay. Then, the antibodies were screened by an ELISA-array with a double-antibody sandwich ELISA format. The antibodies which produced cross-reactivity and low-positive signals were excluded. Finally, six antibodies were selected as capture antibodies. Another monoclonal antibody, 2A10, which could specifically react Title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses", "Passage: Using 4D5, 2B5, 1F1, 2B8, 4F9, and 4E11 as capture antibodies, detection antibodies were coupled to biotin-NHS ester at 4\u00b0C for 3 h according to the manufacturer's instructions. Unincorporated biotin was removed by Desalt spin column . Immunologic reactions were reported by Streptavidin-HRP and Super Signal ELISA Femto Maximum sensitive substrate. Purified goat-anti mouse antibody was used as a positive control.", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: the absence of control measures . Title: The Failure of R (0)\nPassage: The threshold nature of R 0 is used to monitor and control severe real-time epidemics; control measures are often concluded if R 0 < 1 , making the problems with R 0 more than just theoretical. Due to the inconsistencies in calculation, different diseases cannot be compared unless the same method was used to calculate R 0 ; if HIV has an R 0 of 3 and swine flu has an R 0 of 4, we cannot conclude that swine flu is worse than HIV if different methods were used to determine these values. All we can conclude is that Title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus", "Passage: Researches showed that the R 0 of severe acute respiratory syndrome was about 2.7-3.4 or 2-4 in Hong Kong, China . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 . The transmissibility of the Middle East respiratory syndrome is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 , with the inter-human transmissibility of the disease was about Title: The Failure of R (0)", "Passage: While the first factor may be fairly uniform across outbreaks, the second may depend significantly on context, varying both within and among populations. The problem with the SARS estimates stems from the mass-action assumption of compartmental models; that is, that all susceptible individuals are equally likely to become infected. When this assumption does not hold, the models may yield inaccurate estimates or estimates that do not apply to all populations. R 0 estimates for SARS in the field were based largely on outbreak data from a hospital and a crowded apartment building, with anomalously high rates of close contacts among", "Title: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features\nPassage: has spread to more than 191 countries and emerged as the fi rst pandemic virus of this century. Fortunately, this virus causes a low mortality and hopefully this pandemic will be as mild as the last two infl uenza pandemic that occurred in 1957 and 1968. The fear that this virus may become more virulent and lead to a more severe pandemic as occurred in 1918 still exists. We therefore need to be vigilant and prepared if this happens in subsequent waves. Title: Influenza A H1N1 2009 (Swine Flu) and Pregnancy", "Passage: The influenza A virus has been responsible for three global pandemics in the last century: the Spanish Flu in 1918, Asian Flu in 1957 and the Hong Kong Flu in 1968. These pandemics were responsible for a large number of fatalities, the Spanish Flu being the most severe and caused severe pneumonias, particularly among pregnant women . A recently published epidemiological study about cohorts born in and around the pandemic estimated that the individuals born had a . Title: Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment\nPassage: H1N1 viruses as the cause of seasonal influenza from 1957 to 1968. In 1968 a third pandemic was caused by an H3N2 virus, which replaced H2N2 viruses and continues to circulate in humans to the present day. Influenza A pandemics are associated with significant mortality, morbidity, and financial burden. Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: The current outbreak of swine infl uenza that originated in Mexico in March 2009 has spread to more than 80 countries causing more than 3,99,232 laboratory confi rmed cases of pandemic infl uenza H1N1 globally and over 4735 deaths reported to World Health Organization as of 11 October 2009 . The WHO declared pandemic alert stage 6 on 11 June 2009, indicating an ongoing infl uenza pandemic . The 2009 swine fl u virus designated H1N1 A/swine/California/04/2009 is not zoonotic swine fl u and is not transmitted from pigs to humans, but rather from person to person and has higher", "Title: Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1\nPassage: observed at the ambient temperature of 4uC . The average temperature was approximately two degrees lower than the desired reaction temperature of 60uC. Additionally, the temperature of the devices tended to decline from their steady state during the last 20 minutes of the reaction . The temperature profiles at the ambient temperature of 37uC, however, were similar to those at 28uC. Title: Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1", "Passage: observed at the ambient temperature of 4uC . The average temperature was approximately two degrees lower than the desired reaction temperature of 60uC. Additionally, the temperature of the devices tended to decline from their steady state during the last 20 minutes of the reaction . The temperature profiles at the ambient temperature of 37uC, however, were similar to those at 28uC. Title: Cas12a-Based On-Site and Rapid Nucleic Acid Detection of African Swine Fever\nPassage: To evaluate the stability of the lyophilized CORDS assay, the individual tubes were incubated at 37 \u2022 C for 24, 72 or 168 h before verification. Each tube C was stored at 4 \u2022 C for 168 h before verification. Title: Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1", "Passage: consistent between all three heaters and the thermalcycler . Since the RT-LAMP assay requires a constant temperature of 60uC for the length of the amplification reaction, the temperature profiles of the sample wells were compared over the course of the incubation and between all three NINA heaters. A representative temperature profile is displayed in Figure 2 , showing a steady reaction temperature at or close to 60uC for length of amplification reaction. During the 60 minute incubation, the average temperature for each device was 60.2, 59.8, and 59.7 . The minimum temperature achieved during the reaction reflects the fact that", "Title: Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1\nPassage: Estimates of the attack rate for Influenza vary greatly. In the authors report an attack rate of 68% among servicemen during an H1N1 outbreak in Finland during the winter of 1977-78. Among the 1575 surveyed in La Gloria an attack rate of 39% was observed. Finally, a recent report in Peru indicates that 33% of cases were asymptomatic, meaning that the attack rate in La Gloria could actually be as high as 58% if we Figure 2 Simulation results for the estimate of the mean of the serial interval. The first boxplot in each frame shows results when all the Title: Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016", "Passage: A total of 1722 patients aged \u226518 years hospitalized with laboratory-confirmed influenza were recorded: 805 were aged 18-64 years and 917 \u2265 65 years and 743 were female. During the six seasons studied, 1480 patients were infected with influenza A viruses and 241 with influenza B viruses. Title: Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016\nPassage: Of the 1722 patients, 96 were admitted to a hospital for a reason other than acute respiratory infection and developed ILI symptoms \u226548 h after admission and were classified as nosocomial influenza. Of these 96 cases, 35 were aged 18-64 years, 22 were aged 64-74 years, 39 \u2265 75 years and 43 were female. Eighty patients presented \u22651 influenza risk factor and 36 had received the influenza vaccine . Title: Invasive bacterial infections following influenza: a time\u2010series analysis in Montr\u00e9al, Canada, 1996\u20132008", "Passage: 1.0376 for each additional influenza B-positive test result that same week and by 1.0354 for the same increase the preceding week . The combined effect of both weeks is the product of these IRR, 1.0743. The average weekly influenza B count being 1.1479, its effect over these 2 weeks is to multiply the S. pyogenes case count by 1.0743 1.1479 = 1.0858, an 8.6% increase. With an average of 59 S. pyogenes cases per year in Montr\u00e9al, this represents about five extra cases every year.", "Title: Estimating the number of infections and the impact of non-\nPassage: to date \u2014 the attack rate - is estimated to be highest in Spain followed by Italy and lowest in Germany Title: Estimating the number of infections and the impact of non-\nPassage: Italy 9.8% Title: Estimating the number of infections and the impact of non-\nPassage: infected as of March 28th, giving an attack rate of 9.8% of the population . Spain Title: Estimating the number of infections and the impact of non-\nPassage: infected to date. Germany is estimated to have one of the lowest attack rates at 0.7% with 600,000", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: It is known that influenza virus infections are often accompanied by other viral pathogens . Depending on the detection method different ratios of co-infections have been found. Analysis by qRT-PCR revealed that 54.5-83.3% of influenza A or B positive patients were found to have at least one concomitant respiratory viral infection . The detection frequency with immunofluorescence was found to be even higher . Potential concomitant viral pathogens of influenza virus infections include human rhinovirus , respiratory syncytial virus, adenovirus, human coronavirus, human metapneumovirus and parainfluenza virus . Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Two virus strains were selected for those experiments, one being the most sensitive to carrageenan pdm) and one being the least sensitive . In both cases the isobolograms show a synergistic interaction of carrageenan and Zanamivir . Thus, it was shown that Zanamivir and carrageenan target individual influenza viruses with different efficiencies, most probably due to their different antiviral strategies. As a result, the combination provides synergistic activity with higher protection against a broader spectrum of influenza virus strains than the individual compounds. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: During the evaluation process we found that the binding efficiency of different carrageenan subtypes on different influenza strains varies. The combined use of iota-and kappa-carrageenan for the treatment of lethally influenza infected C57Bl/6 mice revealed a better therapeutic effect than the use of iota-carrageenan alone . Thus, to provide a broader spectrum of activity against different influenza virus strains, a mixture of iota-and kappa-carrageenan was used for further evaluation. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: to the broad antiviral effectiveness of carrageenan, patients will receive in parallel a treatment of concomitant viral infections. Therefore, patients will benefit from a decreased probability to develop complications. In consideration of the complications known to accompany an influenza virus illness this combinational therapy meets an urgent medical need.", "Title: DNA methylation signatures in peripheral blood strongly predict all-cause mortality\nPassage: Response: We regret the confusion. As done in other epigenetic studies in this field 1-3 , which commonly adjusted for basic confounding factors, including age, sex, and batch effects, we included those factors as covariates in the genome-wide screening phase. Limited adjustment in the EWAS screening phase also allows more potential biologically relevant candidates to enter the validation phase in which the most thorough correction for potential confounding factors and multiple testing were employed. A flowchart for study design and data analysis has now been added as suggested . Title: Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer", "Passage: To our knowledge, this is the first report of tumour DNAmethylation patterns leading to the identification of a germline susceptibility locus, underscoring the value of TCGA. Recent studies suggest a strong genetic component to inter-individual variation in tumour DNA methylation, and demonstrate both cis-and trans-associations between genotypes and DNA methylation 27 . In addition, methylation quantitative trait loci were found to be enriched for expression quantitative trait loci. It has also been shown that epimutation is associated with genetic variation, for example, associations have been demonstrated between 5 0 UTR MLH1 variants and MLH1 epigenetic silencing 28 32 , the Title: DNA methylation signatures in peripheral blood strongly predict all-cause mortality", "Passage: D NA methylation , as the most widely studied form of epigenetic programming, has been revealed to be modulated by lifestyle and environmental factors 1, 2 and to be involved in onset and progression of complex diseases, including various forms of malignant diseases, cardiovascular diseases , metabolic diseases , neuropsychiatric disorders and autoimmune disorders . Therefore, DNAm could plausibly be associated with the excess mortality from specific diseases and consequently with all-cause mortality. This was exemplified by the previous investigations on smoking-associated DNAm changes and their relationship with lung cancer incidence/mortality and mortality from any cause, cancer and CVD . Title: DNA methylation signatures in peripheral blood strongly predict all-cause mortality", "Passage: In addition, evidence has accumulated that the recently established 'epigenetic clock' based on age-associated DNAm changes, which presumably reflects individuals' biological age, is indicative for ageing-related outcomes and longevity . Following the first study reporting an association of DNAm age with all-cause mortality by Marioni et al. 13 , the association was consistently demonstrated in various longitudinal studies 15, 16 , for individual age-associated CpGs 17 and also for newly identified age-associated CpGs 18 . On the other hand, several epigenome-wide association studies have pointed out that DNAm involved in ageingrelated phenotypes are largely distinct from the established ageassociated DNAm", "Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System\nPassage: and Listeria monocytogenes are preferable carriers for DNA vaccines. is not yet fully understood for many species. The suggested mechanism is based on the bacterial invasion properties . Thus, some invasive bacteria, such as Salmonella typhimurium and Listeria monocytogenes are preferable carriers for DNA vaccines. , and inside the DCs, the antigen gene is expressed as protein, which will later be presented by class I or II MHC and delivered to CD4+ or CD8+ T cells. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: as a mucosal delivery system for antigens from non-Salmonella pathogens . These studies have demonstrated the utility of live bacteria to deliver expressed antigens and DNA vaccines to the host immune system . Since then several other intracellular bacterial vectors have been successfully tested for their capability to deliver a variety of antigens from various pathogens, as well as vaccination against cancer. One genus which has been widely tested as vector is Listeria. Listeria species are Gram-positive intracellular food-borne pathogens. The advantages of Listeria are that it can invade a variety of cells, including antigen presenting cells . After invading Title: Live Bacterial Vectors\u2014A Promising DNA Vaccine Delivery System", "Passage: Lactococcus lactis is the most-studied LAB since its genome is easily manipulated, and many genetic tools have been engineered for L. lactis . Notably, one of the main advantages of using L. lactis as a DNA vaccine carrier is its ability to pass through the intestinal tract without colonization . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: the host cell, Listeria resides inside the phagosome; however, it can escape the phagosome with the help of listeriolysin O and reside in the cytoplasm of the cells, thereby efficiently presenting antigen to both CD8 and CD4 T cells . Several studies have demonstrated the effectiveness and ease of using Listeria monocytogenes to deliver heterologous vaccine antigens and DNA vaccines Jensen et al., 1997; Johnson et al., 2011; Peters et al., 2003; Shen et al., 1995; Yin et al., 2011) .", "Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain\nPassage: . For instance, estimates of pandemic excess respiratory death rates have ranged from 6.1 per 10,000 for the Canary Islands to 169.7 per 10,000 for Burgos . Moreover, approximately 40% of between-province variation in cumulative excess death rates in Spain during 1918-1919 are explained by spatial factors, such as latitude, population density, and the proportion of children, have explained . However, in few of these analyses did researchers take into account a recrudescent wave in Spain, which peaked in Madrid in late December 1919 and in later months in the rest of Spain . Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: Spain experienced one of the highest excess mortality rates during the 1918 influenza pandemic in Europe , although this country did not take part in World War I. Perhaps this pandemic outcome is associated with the fact that Spain was going through a demographic transition and experiencing elevated death rates that were only comparable to those of eastern Europe. Of note, the life expectancy in Spain was 41 years in 1910 and 40 years in 1920 . Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: The 1918-1920 influenza pandemic, or the so-called Spanish flu, was responsible for more than 50 million deaths worldwide . In Europe, the excess mortality rate associated with the 1918-1919 influenza pandemic has been estimated at 1.1%, or approximately an 86% increase in all-cause mortality . This pandemic rapidly spread in a series of pandemic waves that gripped the world beginning in early 1918 . However, according to results of various phylogenetic and molecularclock analyses, the initial circulation of the virus from avian or swine and other mammal species to humans may have occurred a few years earlier . Moreover, the Title: Natality Decline and Spatial Variation in Excess Death Rates During the 1918\u20131920 Influenza Pandemic in Arizona, United States", "Passage: The Spanish Flu of 1918-1920 was called \"the mother of all pandemics\" due to its devastating global mortality impact, estimated at 50 million deaths, or 1%-2% of the world population at the time . The case fatality rate of this pandemic is estimated at approximately 2.5%-several-fold higher than that of typical seasonal influenza epidemics . Another salient feature of this pandemic is the atypical peak of mortality among young adults . Multiple pandemic waves occurred during 1918-1920, and areas in the Northern Hemisphere were more likely to experience a \"herald wave\" in early 1918 . While our understanding of the", "Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome\nPassage: Previous studies demonstrated that the N-terminal 40 amino acids of the SARS-CoV E protein are important for ion channel formation, and that mutations N15A and V25F ] prevent ion conductivity . In addition, the SARS-CoV 3a protein contains a cysteine-rich domain that is involved in the formation of a homodimer to generate the ion channel . Thus, mutation of the cysteine-rich domain blocks the ion conductivity by the 3a protein . To this end, we substituted amino acids Cys-127, Cys-130, and Cys-133 within the cysteine-rich domain of the SARS-CoV 3a protein with serine to generate a lentivirus expressing the ion Title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome", "Passage: It is increasingly evident that NLRP3 detects RNA viruses by sensing the cellular damage or distress induced by viroporins , transmembrane pore-forming proteins, encoded by certain RNA viruses; these proteins alter membrane permeability to ions by forming membrane channels . A recent study shows that the SARS-CoV E protein, which comprise only 76 amino acids, forms Ca 2+ -permeable ion channels and activates the NLRP3 inflammasome . Although the E and 3a proteins of SARS-CoV, which comprise 274 amino acids and contain three transmembrane domains , are thought to act as Na + /K + and K + channels, respectively Title: Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels\nPassage: the structure of SARS virus S2 protein 34 as a search probe . Title: Progress of small molecular inhibitors in the development of anti-influenza virus agents", "Passage: The M2 ion channel protein is a transmembrane protein that possesses the activities of typical ion channels . Influenza B lacks an M2 ion channel protein, but the B/M2 protein functions as an M2 ion channel protein during the assembly of the virus . The M2 and B/M2 proteins play important roles in the incorporation of the viral ribonucleoprotein complex into the virus during the assembly process.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: As RV, RSV, and IFV were the most frequently studied viruses in chronic airway inflammatory diseases, most of the viruses listed are predominantly these viruses. However, the mechanisms stated here may also be applicable to other viruses but may not be listed as they were not implicated in the context of chronic airway inflammatory diseases exacerbation . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of the classical symptoms of chronic airway inflammatory diseases . In addition, the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 and bactericidal/permeabilityincreasing fold-containing family member A1 are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway Akram et al., 2018) . These factors may serve as targets to prevent viral-induced exacerbations during the management of acute exacerbation of chronic airway inflammatory diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: exacerbations but to a much lesser extent . More recently, other viruses including bocavirus , human metapneumovirus , certain coronavirus strains, a specific enterovirus strain EV-D68, human cytomegalovirus and herpes simplex virus have been reported as contributing to acute exacerbations . The common feature these viruses share is that they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s ; with bacterial infections previously considered as the likely culprit for acute exacerbation . However, with the advent of PCR technology, more viruses were recovered during acute exacerbations events and reports implicating their role emerged in the late 1980s . Rhinovirus and respiratory syncytial virus are the predominant viruses linked to the development and exacerbation of chronic airway inflammatory diseases . Other viruses such as parainfluenza virus , influenza virus and adenovirus have also been implicated in acute", "Title: Missing and accounted for: gaps and areas of wealth in the public health review literature\nPassage: of individual studies, providing a more accurate estimate of the effects of an intervention . Rigorous synthesis of primary research minimizes bias , explains differences among studies relating to the same research question , and presents more precise and consistent summary statistics than the effect sizes found in individual studies . Well-conducted reviews provide high-quality, accurate evidence , increasing decision-makers' confidence in the strength of the review evidence and in applying the findings in practice . Public health decision makers prefer using systematic reviews to assist in decision-making given that review level evidence saves time and is more efficient compared Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: in review literature, in 25 other sub-topic areas there was a wealth of systematic review literature of moderate or strong quality, including but not limited to, alcohol abuse/use, smoking cessation, women's health, cancer, cardiovascular disease, lifestyle behaviours, disease transmission, depression, diet, healthy weight, exercise, and HIV. In these areas offering many reviews, most had 15 or more which were of strong methodological quality. While review groups can identify and fill gaps in areas where evidence is lacking, there is also an opportunity to produce higher level syntheses where good-quality review evidence is available. Based on this analysis of the published, Title: Missing and accounted for: gaps and areas of wealth in the public health review literature", "Passage: There are promising indicators of demand for reviews, including actions being taken to promote the use of reviews , an awareness of sites providing access to review-level evidence and an increasing number of groups generating summaries of reviews . Despite this heightened activity, given the gaps, a greater investment is needed to provide an evidence base that can meet demand and determine how to apply existing good quality systematic reviews in different contexts . Organizations involved in the conduct of systematic reviews should direct synthesis funding to areas lacking in review content, or should consider higher-level reviews of reviews , Title: Cochrane Systematic Reviews of Chinese Herbal Medicines: An Overview\nPassage: based on how well the review scored on the first 9 questions.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The first viral isolate was patented and concerns were raised that this would restrict access to both the virus and to viral diagnostics . However, sensitive, validated reverse transcriptase real-time polymerase chain reaction -based diagnostics were quickly described and virus was made freely available subject to routine biosafety considerations . Subsequent epidemiology and research has identified the cell receptor as exopeptidase dipeptidyl peptidase 4 ; that MERS-CoV has a broad tropism, replicating better in some cells lines and eliciting a more proinflammatory response than SARS-CoV; is widespread in DCs; has the potential to infect other animals and that MERS kills Title: Haunted with and hunting for viruses", "Passage: discovery of new pathogens. Soon the receptor used by MERS-CoV to enter the host cells was identified and the molecular basis of the receptor binding to the virus was also elucidated recently . Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The detection of MERS-CoV antigen has not been common to date but the combination of short turnaround time from test to result, high throughput and identification of viral proteins makes this an attractive option. Detection of viral proteins rather than viral RNA indicates the likely presence of infectious virus. The first rapid immunochromatographic tool described could detect recombinant MERS-CoV nucleocapsid protein from DC nasal swabs with 94 % sensitivity and 100 % specificity compared to RT-rtPCR . A different approach used a monoclonal antibody-based capture ELISA targeting the MERS-CoV nucleocapsid protein with a sensitivity of 10 3 TCID 50 and", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The detection of MERS-CoV antigen has not been common to date but the combination of short turnaround time from test to result, high throughput and identification of viral proteins makes this an attractive option. Detection of viral proteins rather than viral RNA indicates the likely presence of infectious virus. The first rapid immunochromatographic tool described could detect recombinant MERS-CoV nucleocapsid protein from DC nasal swabs with 94 % sensitivity and 100 % specificity compared to RT-rtPCR . A different approach used a monoclonal antibody-based capture ELISA targeting the MERS-CoV nucleocapsid protein with a sensitivity of 10 3 TCID 50 and Title: Development of a Rapid Diagnostic Test Kit to Detect IgG/IgM Antibody against Zika Virus Using Monoclonal Antibodies to the Envelope and Non-structural Protein 1 of the Virus", "Passage: Monoclonal antibodies showing high affinity constant to recombinant proteins were selected among the various hybridoma types. IgG1 from hybridoma J5E1 showed a 1.5 to 10 fold strong affinity to recombinant E antigen compared to isotypes from other hybridomas . On the other hand, IgG1 from hybridoma J2G7 showed an even stronger response to recombinant NS1 antigen, with a 5 to 100 fold strong affinity to NS1 protein compared to isotypes from other hybridomas . Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "Passage: In-house anti-SARSr-CoV IgG and IgM ELISA kits were developed using SARSr-CoV Rp3 NP as antigen, which shared above 90% amino acid identity to all SARSr-CoVs, as reported previously . For IgG test, MaxiSorp Nunc-immuno 96 well ELISA plates were coated overnight with recombinant NP. Human sera were used at 1:20 dilution for 1 h at 37\u00b0C. An anti-Human IgG-HRP conjugated monoclonal antibody was used at a dilution of 1:40,000. The OD value was calculated. For IgM test, Maxi-Sorp Nunc-immuno 96 wellELISA plates were coated overnight with anti-human IgM . Human sera were used at 1:100 dilution for 40 min at Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Some sero-assays have bypassed the risks of working with infectious virus by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins , or using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase . A pseudo particle neutralization assay has seen widespread used in animal studies and was at least as sensitive as the traditional microneutralization test. ] Studies using small sample numbers and ppNT found no evidence of MERS-CoV neutralizing antibody in sera from 158 children with LRT infections between May 2010 and May 2011, 110 sera from 19 to 52 year old male blood", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: The ANDV-Syrian hamster model has a number of features in common with the human disease, as well as some differences. Unlike the neurologic diseases that have been possible to elicit with HTNV, the hamster model for HCPS appears to be caused by capillary leak that results in pulmonary edema and the production of a pleural effusion with exudative characteristics. Typically the hamsters die between 11 and 14-d post-inoculation, reflecting a slightly accelerated incubation period in comparison to human infections. As with human HCPS, the microscopic examination of the lung reveals abundant fibrin deposition, thickened alveolar septa, and viral antigen expressed Title: Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters", "Passage: Small-animal models are invaluable tools to study the pathogenesis of diseases caused by neglected infectious disease agents such as Andes virus. However, the utility of the hamster model, as well as the role of the immune response in hantavirus disease pathogenesis, is contentious. Previously, we and others have demonstrated that the ablation of adaptive T and B cell responses to ANDV infection in hamsters does not alter the course of disease . Here, using the Syrian hamster/Andes virus lethal disease model, we demonstrate that another component of the immune system is not directly responsible for the HPS-like disease cause by Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens", "Passage: Testing models of pathogenesis can be done more effectively when there is an animal model that mimics key aspects of the disease. There is no such model that closely mimics HFRS, but animal models exist for both the asymptomatic carriage of PUUV and SNV by their native carrier rodents, the bank vole Myodes glareolus and the deer mouse P. maniculatus; as well as a Syrian hamster model using ANDV or the related Maporal virus from Venezuela, for which an HCPS-mimetic disease is observed . Title: A New Model for Hendra Virus Encephalitis in the Mouse\nPassage: here between old and young mice, it raises the possibility that following longer periods of observation illness may develop in young mice.", "Title: mRNA pseudoknot structures can act as ribosomal roadblocks\nPassage: lacZ transcript by reducing 3 0 -end exonucleolytic attacks . The core plasmid contained no distinct transcription termination signal after the lacZ gene, and accordingly we found transcripts that exceeded far beyond the full-length Fl band . Title: Can\u2019t RIDD off viruses", "Passage: Cleavage substrates Beside 28S rRNA, predominantly cleaves mRNAs encoding ribosomal proteins Xbp1u and other mRNAs in addition to microRNA precursors which are targeted as part of the RIDD pathway Selection of cleavage site Cleaved between 2nd and 3rd nucleotide positions of UN/N sites RNA sequence with the consensus of 5 -CUGCAG-3 in association with a stem-loop structure essential for recognition of Xbp1u and other mRNAs association of RNaseL mutations with generation of prostate cancer extends the ambit of influence of this anti-viral effector to more non-infectious physiological disorders . Biochemically, the similarity in their RNase domains does not extend to Title: Can\u2019t RIDD off viruses", "Passage: Cleavage substrates Beside 28S rRNA, predominantly cleaves mRNAs encoding ribosomal proteins Xbp1u and other mRNAs in addition to microRNA precursors which are targeted as part of the RIDD pathway Selection of cleavage site Cleaved between 2nd and 3rd nucleotide positions of UN/N sites RNA sequence with the consensus of 5 -CUGCAG-3 in association with a stem-loop structure essential for recognition of Xbp1u and other mRNAs association of RNaseL mutations with generation of prostate cancer extends the ambit of influence of this anti-viral effector to more non-infectious physiological disorders . Biochemically, the similarity in their RNase domains does not extend to Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: Most viroids are often enzymatically active ribozymes -yet they are examples that this trait can get lost as a result of changing environmental conditions. Loss of ribozyme activity is a functional, not a genetic loss. Only the nuclear variants, the Pospiviroidae, can lose their ribozyme activity and use the cellular RNase III enzyme for their replication. In contrast, the Avsunviroidae are still active hammerhead ribozymes. Thus, inside the nucleus of a host cell, the enzymatic RNA function can become unnecessary. Not genes, but a function, the catalytic activity, gets lost.", "Title: Influenza A H1N1 2009 (Swine Flu) and Pregnancy\nPassage: from humans, birds and pigs. Title: Influenza A H1N1 2009 (Swine Flu) and Pregnancy\nPassage: Although the outbreak of influenza A H1N1 2009 appeared first in Mexico in April 2009, this was followed by a growing number of cases reported across the globe. The outbreak of the novel A H1N1 virus was declared a global pandemic by the World Health Organisation from 11 June 2009 until 10 August 2010. These pandemics happen when a new influenza virus, to which the population has little or no immunity emerges and starts to spread. Unlike seasonal influenza, high rates of disease due to a pandemic virus may occur throughout the year. Swine flu is a novel strain of Title: Origins of the 1918 Pandemic: Revisiting the Swine \u201cMixing Vessel\u201d Hypothesis", "Passage: The simultaneous outbreaks of influenza in humans and pigs during the 1918 pandemic naturally raised questions about whether the virus had transmitted from pigs to humans, or humans to pigs. At the time, Koen noted that the flu outbreaks appeared to represent a novel disease in pigs, whereas humans had a long history of influenza pandemics, which suggested that humanto-swine transmission was more likely. Almost a century later, the reconstruction of a 1918 virus from human tissues preserved in Alaskan permafrost and autopsy blocks indicated that the virus's genes appeared to have avian origins . But this did not end Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus", "Passage: The current outbreak of swine infl uenza that originated in Mexico in March 2009 has spread to more than 80 countries causing more than 3,99,232 laboratory confi rmed cases of pandemic infl uenza H1N1 globally and over 4735 deaths reported to World Health Organization as of 11 October 2009 . The WHO declared pandemic alert stage 6 on 11 June 2009, indicating an ongoing infl uenza pandemic . The 2009 swine fl u virus designated H1N1 A/swine/California/04/2009 is not zoonotic swine fl u and is not transmitted from pigs to humans, but rather from person to person and has higher", "Title: Multi-criteria decision analysis as an innovative approach to managing zoonoses: results from a study on Lyme disease in Canada\nPassage: the validity of analysis. Title: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies\nPassage: of imputation were used to obtain the ORs. The imputation had little effect on the univariable analyses, therefore summary statistics from these analyses are based on the observed data. In a sensitivity analysis, a complete case analysis was performed and adjusted ORs were estimated for all of the baseline variables excluding BMI. Estimates similar to those based on multiple imputation were obtained . Title: Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data", "Passage: As proof of principle for GLM, we first tested it on the anion gap, a result calculated by subtracting the serum concentrations of the anions chloride and bicarbonate from those of the cations sodium and potassium, and confirmed that our methods found a rule for elevated anion gap based on these four items. Title: The Screening Research of NF-\u03baB Inhibitors from Moutan Cortex Based on Bioactivity-Integrated UPLC-Q/TOF-MS\nPassage: Analysis. The test results were represented with mean \u00b1 SEM. And t-test was used for comparison of significant differences among different groups. SPSS v.18.0 statistical analysis software was used for statistical analysis. Results with values of P < 0.05 were considered statistically significant.", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: While the lower airway is the site of dysregulated inflammation in most chronic airway inflammatory diseases, the upper airway remains the first point of contact with sources of exacerbation. Therefore, their interaction with the exacerbation agents may directly contribute to the subsequent responses in the lower airway, in line with the \"United Airway\" hypothesis. To elucidate the host airway interaction with viruses leading to exacerbations, we thus focus our review on recent findings of viral interaction with the upper airway. We compiled how viral induced changes to the upper airway may contribute to chronic airway inflammatory disease exacerbations, to provide Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: the lower airway environment, resulting in prolong exacerbation episodes following viral infection. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases .", "Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019\nPassage: care workers. A considerable proportion of participants reported symptoms of depression ), anxiety ), insomnia ), and distress ). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers Patient Health Questionnaire scores among physicians vs nurses: 4.0 vs 5.0 ; P = .007; median Generalized Anxiety Disorder scale scores among men vs women: 2.0 vs 4.0 ; P < .001; median Insomnia Severity Index scores among frontline vs second-line workers: 6.0 vs 4.0 ; P < .001; median Impact of Event Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019", "Passage: and distress was assessed by the Chinese versions of the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, the 7-item Insomnia Severity Index, and the 22-item Impact of Event Scale\u2013Revised, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. RESULTS: A total of 1257 of 1830 contacted individuals completed the survey, with a participation rate of 68.7%. A total of 813 were aged 26 to 40 years, and 964 were women. Of all participants, 764 were nurses, and 493 were physicians; 760 worked in hospitals in Wuhan, and 522 were frontline health Title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019", "Passage: Abstract: IMPORTANCE: Health care workers exposed to coronavirus disease 2019 could be psychologically stressed. OBJECTIVE: To assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China. DESIGN, SETTINGS, AND PARTICIPANTS: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from 1257 health care workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 were eligible. MAIN OUTCOMES AND MEASURES: The degree of symptoms of depression, anxiety, insomnia, Title: Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study", "Passage: evidence that HCWs attend work with symptoms suggestive of communicable disease . Similar to findings here, a study by Blake et al. found a loss in income was associated with the general working population's ability to comply with recommendations during an influenza pandemic in the US, resulting in symptomatic staff in the workplace . A recent survey, also in the US, found that 55% of workers without sick pay compared to 37% with, would attend work with an infectious disease .", "Title: COVID-19 and smoking: A systematic review of the evidence\nPassage: We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases 12 . However, from their published data we can calculate that the smokers were 1.4 times more likely to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers . Title: COVID-19 and smoking: A systematic review of the evidence", "Passage: the disease outcome and smoking status was conducted in that study. Finally, Liu et al. found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking than the group that showed improvement or stabilization , with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression . We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed Title: COVID-19 and smoking: A systematic review of the evidence", "Passage: were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al. 13 found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of Title: COVID-19 and smoking: A systematic review of the evidence", "Passage: disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases. Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases. Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak. Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients\u2019", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: of virus despite the mild symptoms. Title: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\nPassage: Patients with mild symptoms may not present positive signs. Patients in severe condition may have shortness of breath, moist rales in lungs, weakened breath sounds, dullness in percussion, and increased or decreased tactile speech tremor, etc. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus\nPassage: nonspecific symptoms. Title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "Passage: Currently, one urgent and critical challenge is to treat infected patients and save their lives. Several studies have roughly described the overall clinical features of 2019-nCoV patients . However, the more specific and classified clinical characteristics of the infected patients still require further investigation, particularly for those with severe symptoms, which is roughly estimated to be approximately 15-20 percent of totally confirmed cases based on the local data in our hospital. Clinically, for those severe patients, the main symptoms of 2019-nCoV pneumonia are fever, decreased white blood cell and lymphocyte count, increased C reaction protein and abnormally expressed cytokines .", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: in humans . Currently, NA-specific antibody responses are not considered a correlate of protection . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx . LAIV immunization induces serum antibody responses, mucosal antibody responses , and T cell responses. While robust serum antibody and nasal wash antibody responses are associated with protection from infection, other immune responses, such as Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: One of the perceived risks of vaccinating commercial poultry against influenza is the possibility of the vaccine protecting birds from disease without preventing replication and spread of the virus. We have demonstrated that a single dose of LAIV is able to induce stronger innate and mucosal IgA responses and protect young immunologically immature chickens better than a single dose of conventional IIV. Most importantly, priming with LAIV led to a synergistic serum antibody induction by IIV and enhancement of antibody cross-reactivity, thereby increasing the chance of protection from distantly related strains. Our prime-boost vaccine strategy requires further improvements to address Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: Overall, birds in the LAIV-LAIV group showed consistently high mucosal antibody responses across all three ELISA tests . The LAIV-IIV group also showed a good level of antibody response that was somewhat biased toward IgG response despite the fact that the IgA response observed in this group was not significantly different from the LAIV vaccinated groups . The single vaccination regimens administered at 3 weeks of age showed a trend that was similar to the 1-day-old vaccination result: no differences in anti-NP or IgG antibodies and higher IgA responses in LAIV groups compared with IIV groups . Title: Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens", "Passage: decade and it has been reported to protect young individuals better than IIV . Importantly, recent studies showed that LAIV can pre-sensitize the population and, subsequently, synergistically boost the efficacy of IIV . It should be noted that the use of LAIV in poultry requires strict safety standards due to concerns about the possibility that wild type strains may circulate in domestic poultry without apparent clinical symptoms, undergo genetic reassortment with the vaccine virus, and produce novel virulent strains . An ideal poultry LAIV should not be able to revert to wild type virus or undergo reassortment with field strains.", "Title: Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis\nPassage: D 2 DR complex in the electropherograms remarkably decreased; this peak decreased with increasing concentrations of the compound . Dose-response analysis on the claimed inhibitor 1,3dichloro-2-propanol, which is important for small-molecule inhibitor studies, was conducted. Overall, the results indi- cated that 1,3-dichloro-2-propanol remarkably inhibited the D 2 DR/\u03b2-arrestin-2 interaction and is a promising drug for the treatment of Parkinson's disease. Title: Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis", "Passage: More than 40 compounds, including phytic acid, 3-amino ethylamine, and 1,3-dichloro-2-propanol, were added to the mixtures to test the pharmacological regulation of the drugs on the D 2 DR/\u03b2-arrestin-2 interaction. The mixtures were then injected into uncoated fused capillaries and separated by the different charges and sizes. We conveniently obtained information about the interaction from the electropherograms. Some compounds have acute effects on the native structures of the target proteins, whereas others have more moderate regulatory activities on the interaction, which showed more drug-like properties because the physiological regulations are usually reversible. Title: Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis", "Passage: acid has a detectable interaction with \u03b2-arrestin-2 and thereby blocks further binding of \u03b2-arrestin-2 to D 2 DR. Phytic acid is hence a promising therapy for Parkinson's disease. Title: Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis", "Passage: When 33 \u03bcmol/L ethylenediamine was added to the mixture of 2.71 \u03bcmol/L FITC-labeled \u03b2-arrestin-2 and 1.26 \u03bcmol/L D 2 DR, the peak of FITC-arrestin/D 2 DR complex in the electropherogram disappeared , indicating that ethylenediamine strongly inhibited the D 2 DR/\u03b2-arrestin-2 interaction. Therefore, such chemical compounds as ethylenediamine that can inhibit the interaction have potential for use in the treatment of Parkinson's disease. The screening results demonstrated that 1,3-dichloro-2-propanol had inhibition properties similar to those of ethylenediamine. When 33 \u03bcmol/L or 67 \u03bcmol/L 1,3-dichloro-2-propanol was added to the mixture of FITClabeled \u03b2-arrestin-2 and D 2 DR, the peak of FITC-arrestin/", "Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies\nPassage: C. burnetii is a highly pleomorphic Gram-negative coccobacillus and the causative agent of Q fever. Q fever is a zoonosis, and the most common reservoirs are cattle, sheep, and goats but many other animals can be infected by C. burnetii . When infected, these domestic animals can shed the organism in urine, feces, milk, and especially birth products. The pathogen survives within the phagolysosome of host cells, and a spore stage has been described. This spore stage explains the ability of C. burnetii to survive in unfavorable environmental conditions, and it can be an environmental risk for months to years Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: Text: Q fever is a worldwide zoonosis caused by Coxiella burnetii , a small, gram-negative obligate intracellular bacterium. C. burnetii displays antigenic variation with an infectious phase I and less infectious phase II. The primary reservoir from which human infection occurs consists of sheep, goat and cattle. Although C. burnetii infections in animals are usually asymptomatic, they may cause abortions in sheep and goats . High concentrations of C. burnetii can be found in birth products of infected mammals . Humans frequently acquire infection through inhalation of contaminated aerosols from parturient fluids, placenta or wool . Because the infectious dose Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany", "Passage: is very low and C. burnetii is able to survive in a spore-like state for months to years, outbreaks among humans have also occurred through contaminated dust carried by wind over large distances . Title: A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany\nPassage: adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3trimester and to test animals in petting zoos regularly for C. burnetii.", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Some sero-assays have bypassed the risks of working with infectious virus by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins , or using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase . A pseudo particle neutralization assay has seen widespread used in animal studies and was at least as sensitive as the traditional microneutralization test. ] Studies using small sample numbers and ppNT found no evidence of MERS-CoV neutralizing antibody in sera from 158 children with LRT infections between May 2010 and May 2011, 110 sera from 19 to 52 year old male blood Title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera", "Passage: lysates may lead to cross-reactivity, resulting in reduced specificity . High quality filovirus recombinant protein antigens can be safely prepared without the need for high BSL-4 biocontainment facilities and outside EBOV endemic areas. Their use in ELISA has potential to reduce the risk of false positive results and allows for better standardization . Testing clinical specimens potentially containing a BSL-4 viral agent presents a serious biohazard. While a number of inactivation methods were shown to completely inactivate EBOV , they also markedly alter the protein components in human blood, e.g., enzymes and coagulation factors . Results of viral inactivation protocols Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: or luciferase has also been developed. We have recently developed a VSV-based pseudotype bearing Lassa virus GP for the detection of neutralizing antibodies in the sera obtained from a Lassa fever patient. An example of the LASV neutralization assay using the VSV pseudotype is shown . In the presence of serum from Lassa fever patients, the number of GFP-positive cells is significantly reduced compared with the number in the absence of the patient's serum . The control VSV pseudotype bearing VSV GP is not neutralized by any sera. When the cut-off serum dilution is set at 50% inhibition of infectivity Title: Assay Challenges for Emerging Infectious Diseases: The Zika Experience\nPassage: avoidance of cross-reactivity is more easily engineered into molecular tests of virus RNA because primers or probes can be designed to be virus-, antigen-and serotype-specific , it is not as easily achieved for immunoassays .", "Title: Adenovirus flow in host cell networks\nPassage: regard, AdVs are a robust family, composed of more than 100 known serotypes that can infect various vertebrate species including mammals, birds, fish, reptiles and amphibians . To date, there are at least 57 serotypes divided into seven species that can infect humans, causing acute respiratory disease, gastroenteritis, keratoconjunctivits and even obesity . These diseases are generally self-limiting, but severe and deadly infections can occur in immunocompromised hosts . Cell biology studies using optimized tissue culture systems have shown that typical times for producing AdV virions from infected cells ranges from 14 to 19 h depending on serotype , though Title: Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice", "Passage: The ability of human adenoviruses to induce strong innate and adaptive immune responses makes them powerful adjuvants that facilitate the immune response against an encoded antigen. Recombinant adenoviruses have been shown to elicit significant immune responses to bacterial , viral and tumour-associated antigens . While these results are encouraging, immunity eventually develops against virus capsid proteins. This severely reduces the immunogenicity of adenovirus-based vaccines in mice, , primates and humans . This problem is also significant since a large portion of the Western world has marked levels of anti-adenovirus serotype 5 antibodies and is also prominent in regions of sub-Saharan Title: Viral vector-based influenza vaccines", "Passage: Recombinant adenoviruses have attractive properties to serve as vaccine vectors: high titer stocks can be grown, genes of interest can easily be inserted into the stable viral genome, long-term storage at 4 degrees is possible and rAd infects a variety of hosts, tissues and cell types. 184 Furthermore, rAd can even induce robust immune responses when administered orally or intra-nasally, potentially bypassing pre-existing immunity against the vector. 184 Finally, even replicationdeficient rAd are known to be immunogenic; adenovirus 5 is a replication-deficient vector that has been evaluated for gene delivery, anti-cancer therapy and as an infectious disease vaccine. An overview Title: Adenovirus flow in host cell networks", "Passage: In undertaking such work, we will learn more about how cells and viruses work, and at the same time, the knowledge can be used to improve vectors for basic research and therapeutic applications, either by optimizing AdVs for delivery or by transferring certain properties to other types of delivery systems.", "Title: Small synthetic molecule-stabilized RNA pseudoknot as an activator for \u20131 ribosomal frameshifting\nPassage: point of translation reactions . In the absence of NCT8, FE for the M1-VPK construct was 10%, similar to the mRNA variant A-VPK . The highest FE was observed in the mRNA containing F-VPK sequence , which was due to the presence of stable pseudoknot regardless of the presence of the NCT8. In the presence of NCT8 , FE on M1-VPK was increased from 10% to 28%. In contrast, the FE on A-VPK and F-VPK did not change and was 9% and 27%, respectively . Increasing the concentration of NCT8 to 25 M has shown similar FE levels . Title: Enterococcus faecalis FK-23 affects alveolar-capillary permeability to attenuate leukocyte influx in lung after influenza virus infection", "Passage: Figure 1 Administration of LFK protects mice from influenza virus PR8-induced death. The experimental protocol for oral administration and infection with influenza A/PR/8. The vertical arrows indicate oral administration of LFK or saline from day \u22126 to day 17. The triangle on day 0 indicates the inoculation with PR8 . Survival rate of mice after the infection with PR8 . Statistically significant difference between saline and control mice is indicated by P value . Viral titers in the lungs after inoculation with PR8. Mean viral titers \u00b1 standard deviations are shown. Each group consists of 6 to 7 mice. Title: Small synthetic molecule-stabilized RNA pseudoknot as an activator for \u20131 ribosomal frameshifting", "Passage: in FE. An increase in FE was also seen for the M2-VPK construct, where FE was 0.32 \u00b1 0.01% in the absence and 1.70\u00b10.06% in the presence of 0.3 M NCT8. FE in cells that expressed the F-VPK did not change significantly with up to 0.03 M NCT8, but increased at NCT8 concentrations >0.1 M. The changes in FE relative to the background -1PRF in the cells expressing M1-and M2-VPK treated with 0.3 M NCT8 were much higher than those in the F-VPK expressing cells , suggesting the effect of NCT8 on FE in the cells expressing its target sequence. Title: Small synthetic molecule-stabilized RNA pseudoknot as an activator for \u20131 ribosomal frameshifting", "Passage: SDS-PAGE. Frameshifting efficiency, FE, was calculated as the ratio of the FS product relative to the sum of the FS and NFS products . Among different NCTn compounds, the increase in FE was most prominent for NCT8 , therefore we investigated the effect of NCT8 on -1PRF in more de-tail . The FE for the mRNA containing M1-VPK moderately increased from 13 \u00b1 5% in the absence to 20 \u00b1 1% in the presence of 10 M NCT8 . Also for the mRNA containing the M2-VPK sequence, FE increased from 15\u00b11% to 27\u00b13% after the addition of 10 M NCT8", "Title: Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya\nPassage: Across both surveys, 3034 people were enrolled of which 830 were able to be traced back to their compounds and included in the analysis. Those that could not be traced were mainly due to running out of time and inaccurate information provided at the facility. The participants that could not be traced were evenly distributed between years and facilities. Title: Enhancing Time-Series Detection Algorithms for Automated Biosurveillance", "Passage: The DoD diagnosis data contained 1,939,993 facilitysyndrome days from 308 facilities in 48 states with an overall mean of 7.7 counts per facility per day; of the 11 syndromes, respiratory visits comprised the highest percentage and had the highest mean count . The hospital ED data contained 768,195 facility-syndrome days from 340 facilities in 21 states and had an overall mean of 7.8 counts per facility per day; no visits for lymphadenitis and severe injury and death were included because no facilities had a mean count >0.5 per day for these syndromes. Title: Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya", "Passage: Five rural health facilities were identified whose catchments overlapped with community-based crosssectional surveys being performed . Cross-sectional malaria surveys in the health facilities were conducted in October 2011 and in July 2012 to coincide with the bimodal seasonal peaks in malaria transmission. Four of the five health facilities were sampled during both surveys. One facility was replaced for the second year to maximize overlap with the ongoing community work. All patients and accompanying individuals attending the outpatient clinic were recruited for the survey. A questionnaire was administered to all consenting participants to obtain information on malaria indicators and their area Title: Infection prevention practices in the Netherlands: results from a National Survey", "Passage: The presence of surveillance systems for monitoring infection rates varied considerably by infection type. Surveillance for monitoring CAUTI rates was the lowest, with only 17.8% of hospitals with an established system. Additionally, only 20% of hospitals had established systems to monitor urinary catheter placement and duration. Conversely, nearly all hospitals used an established surveillance system for monitoring CLABSI rates , and the vast majority performed a daily check for whether the presence of a central venous catheter was still indicated . Surveillance systems for monitoring VAP rates were present in only 26.2% of hospitals. A surveillance system for monitoring the", "Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats\nPassage: We next characterized a novel alpha-CoV, BtCoV/Rh/YN2012. It was detected in 3 R.affinis and 6 R.sinicus, respectively. Based on the sequences, we defined three genotypes, which represented by RsYN1, RsYN3, and RaGD, respectively. Strain RsYN2 was classified into the RsYN3 genotype. Four full-length genomes were obtained. Three of them were from R.sinicus , while the other one was from R.affinis . The sizes of these 4 genomes are between 28,715 to 29,102, with G+C contents between 39.0% to 41.3%. The genomes exhibit similar structures and transcription regulatory sequences that are identical to those of other alpha-CoVs . Exceptions including three Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats", "Passage: and SARSr-CoV were both detected in R. sinicus from the same cave. We suppose that SARS-CoV and BtCoV/Rh/YN2012 may have acquired ORF7a or ORF9 from a common ancestor through genome recombination or horizontal gene transfer. Whereas, ORF9 of BtCoV/Rh/YN2012 failed to induce apoptosis or activate NF-\u03baB production, these differences may be induced by the divergent evolution of these proteins in different pressure. Title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats", "Passage: The surveillance was performed between November 2004 to November 2014 in 19 provinces of China. In total, 2061 fecal samples were collected from at least 12 Rhinolophus bat species . CoVs were detected in 209 of these samples . Partial RdRp sequences suggested the presence of at least 8 different CoVs. Five of these viruses are related to known species: Mi-BatCoV 1 , Mi-BatCoV HKU8 , BtRf-AlphaCoV/HuB2013 , SARSr-CoV , and HKU2-related CoV . While the other three CoV sequences showed less than 83% nt identity to known CoV species. These three viruses should represent novel CoV species. Virus isolation Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: Yunnan strains such as the WIV1 had no such deletions and can use human ACE2 as a cellular entry receptor. It is interesting to note that the two bat SARS-related coronavirus ZXC21 and ZC45, being closest to 2019-nCoV, can infect suckling rats and cause inflammation in the brain tissue, and pathological changes in lung & intestine. However, these two viruses could not be isolated in Vero E6 cells and were not investigated further. The two retained deletion sites in the Spike genes of ZXC21 and ZC45 may lessen their likelihood of jumping species barriers imposed by receptor specificity.", "Title: Viral vector-based influenza vaccines\nPassage: cases the use of adjuvants was required for the efficient induction of protective antibody levels. 11 Furthermore, the pandemic of 2009 caused by swine-origin influenza viruses of the A subtype taught an important lesson. The production of tailor made pandemic influenza vaccine proved to be a time-consuming process and in many countries vaccines became available after the peak of the pandemic. 12 These limitations of the currently available vaccine production technologies and vaccines underscore the pressing need for gamechanging vaccines. In addition to improving immunogenicity in the high risk groups, novel vaccines are required that induce longlasting immunity against a Title: Reverse Genetics Approaches for the Development of Influenza Vaccines", "Passage: Because of the antigenic drift, influenza vaccines need to be reformulated yearly to ensure that the HA and NA present in the vaccine match those present in circulating seasonal viruses. To date, three types of influenza virus vaccines are approved by the Food and Drug Administration for human use: recombinant viral HA, inactivated virus and live-attenuated viruses . Regardless of the type of vaccine, seasonal influenza vaccines contain antigens from the three circulating influenza virus strains: IAV subtypes H1N1 and H3N2; and IBV . Recently, to improve the efficacy of seasonal influenza vaccines, a quadrivalent influenza vaccine formulation that includes Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Meeting the mandates of seasonal influenza vaccine development is difficult, and to respond to a pandemic strain is even more challenging. Issues with influenza vaccine strain selection based on recently circulating viruses often reflect recommendations by the World Health Organization -a process that is cumbersome. The strains of influenza A viruses to be used in vaccine manufacture are not wild-type viruses but rather reassortants that are hybrid viruses containing at least the HA and NA gene segments from the target strains and other gene segments from the master strain, PR8, which has properties of high growth in fertilized hen's eggs. Title: Viral vector-based influenza vaccines", "Passage: Although currently available influenza vaccines are effective in reducing morbidity and mortality caused by seasonal influenza viruses, they have several limitations. Mainly, continuous antigenic drift of seasonal influenza viruses complicates the production of effective vaccines. The vaccine strains need to be updated almost annually in order to achieve a good antigenic match with the epidemic virus strains. If the vaccine strains do not antigenically match the circulating strains, vaccine efficacy is reduced considerably, as was the case in the 2014-2015 influenza season. Furthermore, the seasonal influenza vaccines will afford little or no protection against antigenically distinct pandemic influenza viruses, which", "Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic\nPassage: Considering the protean evolutionary strategies that influenza has demonstrated, it may be useful to suggest benchmark criteria for an \"ideal\" universal vaccine, so that we can identify targets at which to aim , and so that we can examine knowledge gaps that must be bridged . It should be emphasized that these \"ideals, \" representing vaccine \"perfection, \" may not all be realistic given the many complexities discussed herein. In fact, a truly \"universal\" vaccine that meets all desirable qualities noted-for individual protection, prepandemic protection, and public health control during times of endemic/epidemic drift-will probably remain beyond the reach of Title: Making Universal Influenza Vaccines: Lessons From the 1918 Pandemic", "Passage: The targets of a universal influenza vaccine are therefore many, variable, and constantly changing. The past century has revealed the extraordinary ability-unmatched in communicable disease history-of a single introduced infectious agent to successfully overcome, on a continuing basis, the serial adaptations of population immunity that the virus itself elicits by constant antigenic change. It is a useful, if challenging, thought experiment to realize that even at a minimum, a truly universal influenza vaccine would have to reliably protect against all of the past century's worth of influenza viruses. Not only that, but the ideal universal vaccine would also need to Title: Computational Approaches and Challenges to Developing Universal Influenza Vaccines", "Passage: Traditional approaches have failed to produce stable and protective vaccines for hypervariable and rapidly-evolving viral pathogens, including influenza viruses . The reasons for this failure include inherent uncertainty in pathogen evolution . While global surveillance efforts and data sharing agreements have increased available information, vaccine design often ignores the underlying processes of the global influenza meta-population which generates diversity that allows the viral populations to escape vaccine-induced immune responses and anti-viral treatments. Furthermore, hemagglutination inhibition assay, central to vaccine strain selection, is a poor approximation for the average immune response that does not account for the heterogeneity of immune responses Title: Computational Approaches and Challenges to Developing Universal Influenza Vaccines", "Passage: In the history of fighting infectious diseases, vaccinations are amongst the most cost-effective approaches available to prevent infection. Traditional approaches to vaccine design have been successful against many pathogens. But vaccines that target rapidly-evolving and genetically-diverse disease agents have frequently failed to generate long lasting protection for human populations. This is particularly true for influenza viruses, a single-stranded, negative sense RNA virus. One of the important weapons being developed to effectively prevent influenza virus infection is a vaccine that can provide durable and broadly-reactive protection against multiple subtypes, including those that may cause potential pandemics, that is, a universal influenza", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: A study by Ng et al. showed biomarkers indicative of severe CHIKV infection . They found decreased levels of RANTES and increased levels of Interleukin-6 and Interleukin-1b that could be sued for CHIKV detection in patients as indicators of CHIKV-driven cytokine storm. Couderc et al. demonstrate another cytokine, type-I IFN, as a key player in the progression to CHIKV infection . Using an IFN-a/b null mouse model, they demonstrated evidence of muscles, joints, and skin as privileged CHIKV targets, which is consistent with human pathology. Although Ng et al. concluded that RANTES levels were significantly suppressed in severe CHIKF patients Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: The 2005-2006 epidemic of CHIKV in La Reunion islands in the Indian Ocean, spurred the discovery of a new vector species, Ae. albopictus . Wrecking over one-third of the island's population, this epidemic peaked its devastation between January and February 2006, when over 46,000 cases came into light every week, including 284 deaths . Ae. albopictus is common in urban areas of the United States and is already flourishing in 36 states, raising grave concerns to the immunologically naive populace of the United States . Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: Accordingly, this review elaborately details the epidemiology and global expansion of CHIKV, describes its clinical features and pathogenesis and its symptoms and complications, and finally nominates a possible vaccine approach against CHIKV infection. Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: In recent times, with an increase in global travel, the risk for spreading CHIKV to non-endemic regions has heightened . Several travelers have brought CHIKV home with them after visiting areas with actively infected populations . Such cases have been documented in European countries, Australia, Asia, and the United States . The United States has already reported at least twelve cases of travel-associated CHIKV, while France has reported 850 cases, and the United Kingdom 93 . Beyond this, CHIKV-infected travelers have also been diagnosed in Australia, Belgium, Canada, Czech Republic, French Guiana, Germany, Hong Kong, Italy, Japan, Kenya, Malaysia, Martinique,", "Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1\nPassage: Text: Without specific interventions, the rate of HIV-1 mother-tochild transmission is approximately 15-45% . UNAIDS estimates that last year alone, more than 400,000 children were infected worldwide, mostly through MTCT and 90% of them lived in sub-Saharan Africa. In the most heavilyaffected countries, such as Zimbabwe, HIV-1 is responsible for one third of all deaths among children under the age of five. MTCT of HIV-1 can occur during pregnancy , delivery or breastfeeding . High maternal viral load, low CD4 cells count, vaginal delivery, low gestational age have all been identified as independent factors associated with MTCT of HIV-1 . Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: MTCT of HIV-1 can occur during pregnancy , at delivery and via breastfeeding . HIV-1 can cross the placental barrier in utero either by microtransfusion or by transcytosis across the trophoblast cell layer . IP transmission may occur through direct contact between infant mucosa and HIV-1 infected maternal blood and/ or cervico-vaginal secretions . Finally, HIV-1 in breast milk may result in PP infection of the newborn through mucosal exposure . High maternal viral loads in serum and breast milk and low CD4 cell count as well as obstetric factors such as preterm delivery, vaginal delivery, and prolonged membrane rupture Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: In 2010, UNAIDS estimates that 390,000 children acquired HIV-1-infection worldwide mostly through mother-to-child transmission . Overall transmission rates in the absence of any intervention vary from 12 to 42%. Although antiretroviral therapy can reduce MTCT to as low as 2% , limited access to timely diagnostics and drugs in resource-poor settings blunts the potential impact of this strategy. A better understanding of the mechanisms acting in MTCT of HIV-1 is crucial for the design of interventions other than ART for transmission prevention. Title: HIV testing, test results and factors influencing among infants born to HIV positive mothers in public hospitals of Mekelle City, North Ethiopia: a cross-sectional study", "Passage: There are many ways of HIV transmission. One way of transmission is from an HIV positive woman to her child during pregnancy, labor, and breastfeeding. It is also called vertical transmission which accounts for 14% of all new HIV infections worldwide. In developing countries, despite the availability of proven interventions for the Prevention of Mother-to-Child Transmission , pediatric HIV is still a largely uncontrolled epidemic .", "Title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence\nPassage: Previous work has demonstrated that all cell lines used are capable of mounting a type I IFN response upon viral challenge, with the exception of Vero cells, which possess an IFN-b deficiency . RoNi/7.1 cells have been shown to mount idiosyncratic induced IFN defenses upon viral infection , while PaKiT01 cells are known to constitutively express the antiviral cytokine, IFN-a . This work is the first documentation of IFN signaling induced upon challenge with the particular recombinant VSVs outlined below. We verified known antiviral immune phenotypes via qPCR. Results were consistent with the literature, indicating a less pronounced role for Title: The expression patterns of immune response genes in the Peripheral Blood Mononuclear cells of pregnant women presenting with subclinical or clinical HEV infection are different and trimester-dependent: A whole transcriptome analysis", "Passage: Type-1 interferons. Dendritic cells play a crucial role in linking innate and adaptive immune response and can detect cytokines produced by the infected cells, type-I interferons being most important. It is therefore surprising that despite identifying several upregulated IFN-inducible genes, we did not detect raised expression of IFN\u03b1 or IFN\u03b2 in all the patient groups studied. At protein level, we detected reduced circulating IFN\u03b1 levels in these patients while IFN\u03b2 was not tested . Title: Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-\u03c9 Subtype", "Passage: Cell lines used for cell proliferation and antiviral assays were purchased from ATCC or transferred from collaborators at Kansas State University. Cells were cultured following ATCC's instruction or as previously described . Cell lines used include porcine testis cells , porcine kidney cells , human intestinal epithelial cells , mouse fibroblast cells , mouse kidney cells , and the monkey kidney cells . Title: Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity\nPassage: Peptide restimulation and intracellular cytokine staining 5x10 6 splenocytes were incubated in 96-well round bottom plates in triplicate with Monensin , Brefeldin-A , CW3 peptide SWVPRLYQL , and the CD107a antibody for four to five hours at 37\u00b0C. Cells were surface stained followed by fixation and permeabilization using the cytofix/cytoperm kit . Permeabilized cells were stained with antibodies for TNF\u03b1 , IFN\u03b3 and analyzed by flow cytometry.", "Title: A systematic review of barriers to data sharing in public health\nPassage: WGvP contributed to study design, the literature review and wrote the manuscript. PP contributed to the literature review and manuscript editing. CE contributed to study design, the literature review and manuscript editing. JG contributed to manuscript editing. RW contributed to study design, the literature review and manuscript editing. AJH contributed to the literature review and manuscript editing. DH contributed to study design and manuscript editing. DSB contributed to study design and manuscript editing. All authors read and approved the final manuscript. Title: A bibliometric analysis of IL-35 research from 2009 to 2018\nPassage: further analysis. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: A lay summary of the results will be shared with the participating schools and households, as well as and communities surrounding the schools. Manuscripts will be submitted to appropriate journals discussing the methods, statistical analysis and output, and applications of the data in mathematical modelling of respiratory disease transmission and control. Title: Assessment of Temporary Community-Based Health Care Facilities During Arbaeenia Mass Gathering at Karbala, Iraq: Cross-Sectional Survey Study\nPassage: Have the necessary issues been addressed for the participation of experts in planning and running the MG ?", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: Three cases were aged 65 years or over. All required admission to intensive care and were tourists . These findings could reflect the average older age of the tourist population compared with the local contacts exposed to infection in Europe and do not allow us to draw any conclusion on the proportion of severe cases that we could expect in the general population of Europe. Despite this, the finding of older individuals being at higher risk of a severe clinical course is consistent with the evidence from Chinese case series published so far although the majority of infections in China Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)", "Passage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years . Title: Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season\nPassage: aged 65 years or older . Title: Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China\nPassage: subsequent SIAs did not cover these persons; thus, the immunity gaps among people aged 26 to 45 years increased.", "Title: Chinese journals: a guide for epidemiologists\nPassage: results. However, subsequent studies found little evidence supporting this assertion. Pham et al. found that language bias led to an under-estimation of the protective effect of intervention in RCTs in complementary and alternative medicine systematic reviews but not in that of conventional medicine . Title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study\nPassage: administration of Chinese herbs were supervised by Pharmacy Department of TCM in Shanghai Public Health Clinical Center. Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis", "Passage: For example, the most cited article was a method paper published in The Lancet . This seminal paper changed how method comparison studies are performed in clinical research. The list of the most cited papers also reflected important studies examining the health effects of pharmacological interventions on patients with chronic diseases. Common themes in major advances in health interventions included diabetes control ; Title: Global mapping of randomised trials related articles published in high-impact-factor medical journals: a cross-sectional analysis\nPassage: Forty journals published 39,305 articles, and 23.8% of them were published by four journals with an IF > 30. The Lancet , the Journal of Clinical Oncology and The New England Journal of Medicine published the largest number of articles, followed by The BMJ and Circulation . Most articles were classified as \"medicine, general & internal\" ; \"cardiac & cardiovascular systems\" ; or \"oncology\" according to the WoS journal categorisations .", "Title: Setting healthcare priorities in hospitals: a review of empirical studies\nPassage: setting activity and study objectives. Title: The Tennessee Children's Respiratory Initiative: Objectives, design and recruitment results of a prospective cohort study investigating infant viral respiratory illness and the development of asthma and allergic diseases\nPassage: and environmental factors associated with asthma development, will help in the identification of primary and secondary prevention strategies for asthma. This report describes the study objectives, design and recruitment results of this study cohort. Title: The Tennessee Children's Respiratory Initiative: Objectives, design and recruitment results of a prospective cohort study investigating infant viral respiratory illness and the development of asthma and allergic diseases", "Passage: This report describes the study objectives, design and recruitment results of the Tennessee Children's Respiratory Initiative, designed to investigate the role of respiratory viral infection severity and etiology in asthma development. Future reports will address the complex relationship between infant respiratory viral infection and asthma and atopic diseases. Title: Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1\nPassage: Objectives 4 Clearly describe the primary and any secondary objectives of the study, or specific hypotheses being tested.", "Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China\nPassage: In this section, the performance of the proposed FPASSA to predict the DS1 and DS2 is discussed. It can be concluded from Table 3 that the performance of FPASSA outperformed the compared methods in all measures, whereas the FPA is ranked second. The results of DS2 indicate that the FPASSA is ranked first in terms of RMSE, MAPE, R 2 , and the CPU time. Whereas, the PSO is ranked second, followed by the FPA, GA, then ABC. These results denote that the proposed method can optimize the parameters of the ANFIS model effectively and produce good results in terms Title: Disease dynamics in a stochastic network game: a little empathy goes a long way in averting outbreaks", "Passage: Another notion that enables us to gauge the optimality of equilibria is the Price of Stability . PoS is the ratio of the best possible Nash action profile to the optimum action profile, Title: Optimization Method for Forecasting Confirmed Cases of COVID-19 in China", "Passage: to the ANFIS parameters to enhance time series forecasting because these parameters have a significant effect on the performance of ANFIS. The SI methods include the particle swarm optimization , social-spider optimization , sine-cosine algorithm , and multi-verse optimizer . For example, in SCA algorithm was applied to improve the ANFIS model to forecast oil consumption in three countries, namely, Canada, Germany, and Japan. In the same context, in , The MVO algorithm was used to enhance the ANFIS model to forecast oil consumption in two countries. In addition, in the PSO was used with ANFIS to predict biochar yield. Title: Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy", "Passage: albeit at low levels, and rather disappointingly a recent phase III trial with 2 -OMe-PS SSO was not able to meet its primary endpoint of a statistically significant improvement in the 6 min walk test . Nevertheless, preliminary results with PMO chemistry are promising and further studies are planned to target additional exons . To date, clinical trials have focused on targeted removal of exon 51, since this would benefit the largest patient pool, but SSOs are also being developed to target other exons between 45 and 55.", "Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity\nPassage: Text: Nucleoside analogs have been historically used for anti-cancer chemotherapy because they inhibit cellular DNA/RNA polymerases . More recently, nucleoside analogs have expanded their therapeutic applications and are being used to develop antiviral drugs against a wide range of serious and life-threatening viruses. Some nucleoside analog drugs targeting specific viral polymerases , and sofosbuvir for hepatitis C virus ) have been successful in clinical trials and are currently in use for the treatment of virus-infected patients. Another class of nucleoside analog drugs such as ribavirin, more broadly-acting on various viruses, has been used in conjunction with IFN-\u03b1 . Importantly, extensive Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: The primary mechanism to explain the antiviral effect of nucleoside analogs is based on their direct action on viral polymerization. Nucleoside analogs are transported into the cells and phosphorylated by the consecutive action of viral or cellular kinases, eventually generating nucleotide triphosphates. Mature nucleotide analogs, which are similar to physiological nucleotides, can directly incorporate into the growing viral genome during polymerization, resulting in the termination of chain reaction or the accumulation of mutations . Alternatively, nucleotide analogs can bind to the nucleotide-binding region on viral polymerases and block the entry of incoming natural nucleotides. The other mechanism is based on Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: the accumulation of mutations . Alternatively, nucleotide analogs can bind to the nucleotide-binding region on viral polymerases and block the entry of incoming natural nucleotides. The other mechanism is based on the modulation of cellular nucleoside synthesis. There have been accumulating reports that nucleoside analogs act as antiviral agents by interfering with host nucleoside synthesis pathways . By targeting metabolic enzymes, nucleoside analogs block the natural flow of nucleoside synthesis and consequently cause the depletion or imbalance of NTP pools. As viral replication is highly dependent on the availability of host nucleotides, a nucleotide-defective condition decreases the efficiency of viral Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: the modulation of cellular nucleoside synthesis. There have been accumulating reports that nucleoside analogs act as antiviral agents by interfering with host nucleoside synthesis pathways . By targeting metabolic enzymes, nucleoside analogs block the natural flow of nucleoside synthesis and consequently cause the depletion or imbalance of NTP pools. As viral replication is highly dependent on the availability of host nucleotides, a nucleotide-defective condition decreases the efficiency of viral replication. A more recently proposed mechanism has been based on the observations that a few nucleoside analogs activate innate immunity, especially involving the upregulation of interferon-stimulated genes . Importantly, this phenomenon", "Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: On this occasion information sharing seems to have been rapid and effective . The WHO was notified of the original clustering within days and the full genomic sequence of the new virus was published less than 2 weeks after the cluster was first detected. The WHO has expressed its satisfaction with the actions of the Chinese authorities in sharing information with the WHO. Title: Note from the editors: novel coronavirus (2019-nCoV)", "Passage: Text: The situation has continued to evolve rapidly since then and just a few weeks later, as at 23 January, 614 laboratory-confirmed cases and 17 deaths have been reported including some cases detected outside mainland China . Meanwhile, on 7 January 2020, the novel coronavirus, currently named 2019-nCoV, was officially announced as the causative agent by Chinese authorities . In order to support public health action, viral genome sequences were released by Chinese researchers on 10 January and 2 days later, four further sequences were also made available on the Global Initiative on Sharing All Influenza Data . While more Title: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "Passage: Despite initially restricting what information on the outbreak was shared publicly, the Chinese government has begun to respectfully provide updates on the situation on a daily basis. This encourages the real-time release of information by means of regularly updated situation reports, including epidemiological information with dates of exposure, illness onset, and hospitalization among cases. Title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus", "Passage: can however be found in up to 30% ofpatients negative for influenza viruses . Chinese scientists in Wuhan, who had to deal with an increasing number of acute respiratory tract diseases resembling viral pneumonia, performed deep sequencing analysis from samples taken from the lower respiratory tract and found a \"novel\" coronavirus. The sequence of the complete genome was made public. At the same time, however, the notice from Wuhan brought to mind the SARS- and MERS-epidemics. The measures taken by the Chinese- and WHO-authorities are now well known.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: Intranasal therapy with carrageenan and Zanamivir starting 72 hpi significantly protects lethally influenza H1N1pdm infected mice Next, the minimal effective dose of Zanamivir used as mono-therapy was evaluated in a lethal H1N1pdm mouse model, following the same scheme as described in the H7N7 experiments. The lowest effective dose of Zanamivir after a treatment start 24 hpi was 1 mg/kg BW/ day and its combination with carrageenan was highly effective . In the following experiment the therapeutic potential of the combination with a therapy start 48 or 72 hpi was investigated in comparison with the respective placebo treatment. Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Next, the therapeutic potential of the combination with a delayed therapy start 48 or 72 hpi versus placebo treatment was explored. The survival rates of mice are shown in Fig 2B. All placebo treated mice died until day 10 and also in the group with the treatment start 72 hpi 100% lethality was found. In contrast, the combination therapy starting 48 hpi provided a statistically significant enhanced survival rate in comparison to placebo-treated mice . Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: First, we determined the minimal effective dose of a Zanamivir mono-therapy that significantly improved survival time of H1N1 and H7N7 infected mice. For the H7N7 lethal infection the minimal effective dose of Zanamivir as mono-therapy ranged between 1 and 3 mg/kg BW/ day . Next, we compared the antiviral activity of carrageenan and Zanamivir mono-therapies with the respective combination versus placebo treatment. Survival rates of mice with treatment starting 24 hpi are shown in Fig 2A. All placebo treated mice died between day 7 and 9 and also in all mono-therapy groups 100% lethality was observed until day 15. In Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: For infection experiments, 3-5 weeks old female mice were intranasally inoculated with 50 \u03bcl influenza virus solution containing 2.27x10 3 or 1.65x10 3 plaque-forming unit of H1N1pdm or H7N7, respectively. Subsequently, treatment started 24, 48 or 72 hpi, as indicated for the different experiments. Treatment was performed intranasally either with 50 \u03bcl therapeutic solution or placebo twice per day for 5 days. As therapy either carrageenan ), Zanamivir or a combination of carrageenan and Zanamivir were used. Carrageenan and Zanamivir are used at non-toxic concentrations as shown by and . Mice were monitored twice daily for 15 days for survival", "Title: Neutralization Interfering Antibodies: A \u201cNovel\u201d Example of Humoral Immune Dysfunction Facilitating Viral Escape?\nPassage: The S protein of CoVs is inserted in the envelope of the virion mediating binding and fusion events necessary for infection, and it is the major target of the humoral protective immunity . Although the S protein of SARS-CoV shares little aminoacid identity , it shares common structural features with S proteins of the other members of the Coronaviridae family. SARS-S protein is a type I transmembrane glycoprotein of approximately 1,255 amino acids in length and divided into two functional domains: S1 and S2 . In many CoVs, the S protein is cleaved during biogenesis and these two functional domains Title: Host resilience to emerging coronaviruses", "Passage: Both viral infections elicit a very strong inflammatory response, and are also able to circumvent the immune response. There appears to be several ways that these viruses evade and otherwise redirect the immune response . The pathways that lead to the induction of the antiviral type I interferon response are common targets of many viruses, and coronaviruses are no exception. SARS-CoV and MERS-CoV are contained in double membrane vesicles , that prevents sensing of its genome . As with most coronaviruses several viral proteins suppress the type I IFN response, and other aspects of innate antiviral immunity . These alterations Title: Neutralization Interfering Antibodies: A \u201cNovel\u201d Example of Humoral Immune Dysfunction Facilitating Viral Escape?", "Passage: are held together non-covalently; however, as in the case of human CoV 229E, the S protein is not cleaved in SARS-CoV . The S1 domain forms a globular structure that mediates interaction of the S protein with its main receptor, angiotensin-converting enzyme 2 , while the S2 domain mediates fusion and contains the putative fusion peptide and two conserved helical regions that upon cleavage by the endosomal protease cathepsin L form the six helix bundle fusion core . Title: Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions", "Passage: The modulation of SARS-CoV pathogenesis, for example, was reported to be independent of all three types of interferon signaling mechanisms, with SARS-CoV ORF 3b, ORF 6, and nucleocapsid proteins identified to interfere with interferon signaling through various mechanisms . However, STAT1 has been shown by the same group to be crucial in activating innate immune signaling pathways during SARS-CoV infection, with a secondary role in the prevention of uncontrolled cell reproduction . In contrast, PRRSV appears to be receptive to both IFN-\u03b1 and -\u03b2 dose-dependent treatment ; however, pigs infected with PRRSV do not evoke significant IFN responses, with little", "Title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies\nPassage: Bats are the natural reservoirs of both SARS-CoV and MERS-CoV. SARS-CoV crossed the species barrier into palm civets and other animals in live animal markets in China, which then infected human, while a MERS-CoV ancestral virus crossed species barrier into dromedary camels. Abundant circulation of MERS-CoV in camels results in continuous zoonotic transmission of this virus to human, while SARS-CoV was not found to circulate in the intermediate reservoirs, explaining SARS being a one-off outbreak and MERS a continuing zoonotic disease . Aerosolgenerating procedures such as intubation were associated with increased viral transmission of both CoVs resulting in nosocomial outbreaks Title: CDC Summary 21 MAR 2020,", "Passage: The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The sequences from U.S. patients are similar to the one that China initially posted, suggesting a likely single, recent emergence of this virus from an animal reservoir. Title: Host resilience to emerging coronaviruses\nPassage: is unclear if this is due to the affected patient populations and regions 39 ]. Since MERS-CoV is a very recently discovered virus, more research has been done on SARS-CoV. However, given the similarities it is hoped that some of these findings can also be applied to MERS-CoV, and other potential emerging zoonotic coronaviruses. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan", "Passage: infections and 800 deaths, and Middle East respiratory syndrome CoV which has caused a persistent epidemic in the Arabian Peninsula since 2012 . In both of these epidemics, these viruses have likely originated from bats and then jumped into another amplification mammalian host for SARS-CoV and the dromedary camel for MERS-CoV] before crossing species barriers to infect humans.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: There are several approaches to avoiding pre-existing vector immunity, such as the use of vectors derived from nonhuman sources, using human viruses of rare serotypes , heterologous prime-boost approaches , homologous reimmunization and removing key neutralizing epitopes on the surface of viral capsid proteins . The inhibitory effect of pre-existing immunity can also be avoided by masking the Ad vector inside dendritic cells . In addition, mucosal vaccination or administration of higher vaccine doses can overcome pre-existing immunity problems . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: studies, with the possibility of a competitive exclusion component to immunity not discussed. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: Other studies have evaluated cellular responses. A study by Sevil Dom\u00e8nech and colleagues reported that pre-existing anti-vector immunity seriously compromises CD8 + responses in mice when exposed to a similar strain used as vector . In contrast, another study by the same authors reported that animals exposed to related vectors induce much higher CD8 + responses when compared with animals which do not have any pre-existing Salmonella immunity . The difference between these two studies was that in the first, the prime and boost were with identical serovars, while in the second study, different serovars were used. This may point Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: be an option for short-term or perhaps therapeutic vaccination .", "Title: Incubation periods of viral gastroenteritis: a systematic review\nPassage: 5% of cases will exhibit symptoms by 0.9 days after infection and 95% of cases will become symptomatic by 3.3 days . Title: Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection\nPassage: The clinical course and outcome of all patients are summarized in Figure 1 . In the analysis of 15 patients who visited the emergency department, the mean interval between symptom onset and emergency room visit was 1.7 days \u00b1 1.5 days . In the analysis of all 18 patients, the mean interval between symptom onset and the start of oseltamivir phosphate administration was 3.9 \u00b1 1.6 days . In addition, the mean interval between symptom onset and symptom improvement was 4.7 \u00b1 1.7 days . Title: A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections", "Passage: 'Time from symptom onset' was defined as the duration from the appearance of the first presenting symptom till the time of blood sample collection. The distribution of 'time from symptom onset' in our cohort peaked at 2-4 days after the initiation of symptoms with substantial proportions of patients turning to medical assistance either sooner or later . Figure S7 . Distribution of time from initiation of symptoms . N/A -healthy controls or patients for which data was not obtained. Title: Incubation periods of viral gastroenteritis: a systematic review\nPassage: norovirus cases will exhibit symptoms 0.5 days after infection and 95% of cases will become symptomatic by 2.6 days .", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: The number of mammalian protein-coding genes is about 20,000. Surprisingly, this is only a fifth of the number of genes of bread wheat . Tulips, maize and other plants also have larger genomes, indicating that the number of genes does not necessarily reflect the complexity of an organism. What makes these plant genomes so large, is still an open question. Could the giant genomes possibly be the result to breeding of plants by farmers or gardeners? Title: Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts", "Passage: Unusually, both contigs were also spanned by another open reading frame in the reverse read direction. In general, an open reading frame of such a length would not be expected to occur by chance provided that the nucleotide composition is not highly biased . On the other hand, despite the production of a negative sense copy of the genome during replication, reverse read-direction ORFs are not expected to be expressed in positive-sense RNA viruses. Moreover, most of the 147 SNPs were nonsynonymous with respect to the reverse read-direction ORF, although they never resulted in the introduction of a stop codon. Title: Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins", "Passage: Genomes were assembled using Sequencher 4.1.4 . Putative ORFs >100 amino acids were identified and annotated using SeqBuilder version 11.2.1 . Partial genes or genes that seemed interrupted were analyzed for potential introns using GENSCAN . The potential origin of replication for each genome was identified by locating a canonical nonanucleotide motif and confirming predicted stem-loop structures using Mfold with constraints applied to prevent hairpin formation within the nonanucleotide motif and a folding temperature set at 17 \u2022 C . Final annotated genomes have been deposited to GenBank with accession numbers KR528543-KR528569. Title: Personal genomes, quantitative dynamic omics and personalized medicine", "Passage: and removing PCR artifacts using tools as Picard ). Reads are mapped to the genome and variants are assessed, e.g., mapping with several algorithms, including ELAND II , SOAP , MAQ and Burrows-Wheeler Aligner and Novoalign by \u00a9 Novocraft Technologies . Read re-alignment can be performed, e.g., using Genome Analysis Toolkit , or HugeSeq , to call variants, including implementations with Sequence Alignment Map format Tools , annotation using Annovar , SIFT and Polyphen for determining variant effects on proteomic translation . Furthermore, using a variety of methods the structural variants can be determined. For example the paired-end mapping method", "Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro\nPassage: Since acidification is crucial for endosome maturation and function, we surmise that endosome maturation might be blocked at intermediate stages of endocytosis, resulting in failure of further transport of virions to the ultimate releasing site. CQ was reported to elevate the pH Fig. 1 Comparative antiviral efficacy and mechanism of action of CQ and HCQ against SARS-CoV-2 infection in vitro. a Cytotoxicity and antiviral activities of CQ and HCQ. The cytotoxicity of the two drugs in Vero E6 cells was determined by CCK-8 assays. Vero E6 cells were treated with different doses of either compound or with PBS in the Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion 5 . In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein 6 . Time-of-addition experiment confirmed that HCQ effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV-2, which was also found upon CQ treatment . To further explore the detailed mechanism of action of CQ and HCQ in inhibiting virus entry, co-localization of virions with early endosomes or endolysosomes was analyzed by immunofluorescence Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: Interestingly, we found that CQ and HCQ treatment caused noticeable changes in the number and size/morphology of EEs and ELs . In the untreated cells, most EEs were much smaller than ELs . In CQand HCQ-treated cells, abnormally enlarged EE vesicles were observed , many of which are even larger than ELs in the untreated cells. This is in agreement with previous report that treatment with CQ induced the formation of expanded cytoplasmic vesicles 8 . Within the EE vesicles, virions were localized around the membrane of the vesicle. CQ treatment did not cause obvious changes in the number and Title: Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro", "Passage: analysis and confocal microscopy. Quantification analysis showed that, at 90 min p.i. in untreated cells, 16.2% of internalized virions were observed in early endosome antigen 1 -positive EEs , while more virions were transported into the late endosomal-lysosomal protein LAMP1 + ELs . By contrast, in the presence of CQ or HCQ, significantly more virions were detected in the EEs, while only very few virions were found to be co-localized with LAMP1 + ELs . This suggested that both CQ and HCQ blocked the transport of SARS-CoV-2 from EEs to ELs, which appears to be a requirement to release the", "Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: Influenza is an infectious disease affecting mainly upper respiratory tract worldwide. Influenza virus causes between three and five million severe cases and an estimated 250,000-350,000 deaths annually. In the European Union, there are between 40,000 and 220,000 annual deaths attributable to influenza. However, mortality is only the tip of the iceberg in terms of the disease burden, since influenza also causes a decrease in functional status and increased dependency in the elderly . Estimating the burden of disease caused by influenza is difficult because many cases do not require medical care, or no confirmatory laboratory tests are widely performed to Title: Influenza virus-related critical illness: prevention, diagnosis, treatment", "Passage: Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States and worldwide . In temperate climate countries, including the U.S., influenza activity peaks during the winter months whereas in tropical regions influenza activity may be more variable . Most persons with symptomatic influenza virus infection have self-limited uncomplicated upper respiratory tract illness. One study estimated that during 2010-2016, approximately 8.3% of the U.S. population experienced symptomatic influenza each year . However, complications may result in severe illness, including fatal outcomes. During 2010-2018, an estimated 4.3-23 million medical visits, 140,000-960,000 hospitalizations, and 12, 000-79,000 Title: Comparison of Influenza Epidemiological and Virological Characteristics between Outpatients and Inpatients in Zhejiang Province, China, March 2011\u2013June 2015", "Passage: Influenza virus is estimated to cause 3 to 5 million cases of severe illness and 250,000 to 500,000 deaths each year, while 5%-10% of adults and 20%-30% of children are infected with the influenza virus worldwide . In lower and middle-income countries, influenza could result in large economic burden encompassing direct costs to the health service and households, and indirect costs of productivity losses . Title: Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010\u20132015)\nPassage: During the 2010-2015 seasons 1400 cases of SHCLCI were recorded, 462 required ICU admission and 167 died: 778 were male. The median age was 61 years . The most-affected age group was the \u2265 65 years age group with 633 cases . The median age of the \u2265 65 years age group was 79 years and the mean age was 78.7 years : 296 were aged \u2265 80 years. Of deaths, 111 occurred in patients aged \u2265 65 years and 55 in patients aged > 80 years .", "Title: Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering\nPassage: binding site. We have also optimized the length of two glycine linkers that connect the Ca 2+ binding loop and CD2 to provide sufficient freedom for the loop. The grafted EFloop III of CaM in different protein environments and scaffolds has similar metal binding affinities for La 3+ and Tb 3+ , which implies that the grafted EF-hand loop is largely solvated and functions independently from the host protein or the protein environment. More importantly, using high resolution NMR and 15 N labeled protein, we have shown that both Ca 2+ and La 3+ specifically interact with the residues in Title: Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering", "Passage: Ca 2+ is able to bind to hundreds of cellular proteins over a 10 6 -fold range of affinities ), depending on the nature of the Ca 2+ -modulated events. Ca 2+ binding has been shown to be essential for stabilizing proteins as well as maintaining proper cellular free Ca 2+ concentrations as seen in buffer proteins such as calbindin D 9k and parvalbumin . Generally the Ca 2+ modulated activity is achieved through Ca 2+ -dependent conformational changes in Ca 2+ -binding proteins. For example, one of the ubiquitous intracellular trigger proteins, calmodulin , has been shown to interact Title: Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering", "Passage: We have shown that CD2 is an excellent scaffold protein . It retains its native structure following insertion of the EF-hand motif both in the absence and presence of Ca 2+ ions. This provides the foundation for measuring the intrinsic Ca 2+ binding affinity with minimized contribution of protein conformational change. In addition, the aromatic Grafting approach to probe site-specific metal binding properties of Ca 2+ -binding proteins. Schematic representation of the grafting approach. Any predicted linear Ca 2+ -binding sequence can be inserted into the host protein CD2 domain 1 between residues S52 and G53 without disrupting the integrity Title: Calciomics: prediction and analysis of EF-hand calcium binding proteins by protein engineering", "Passage: affinities of EFloops in CaM. Our grafting method provides a new strategy to obtain site-specific Ca 2+ binding properties and to estimate the cooperativity and conformational change contributions of coupled EF-hand motifs. We have shown that the contribution of the cooperativity and conformational change to the Ca 2+ affinity for the C-terminal is 40% greater than that for the N-terminal. The same approach will be used to probe the site-specific Ca 2+ affinity of bacterial proteins. Furthermore, we have applied high resolution pulsed-fieldgradient diffusion NMR and analytical ultracentrifugation to investigate the oligomeric state of the isolated EF-loop III of CaM", "Title: Phleboviruses and the Type I Interferon Response\nPassage: In addition to direct antiviral effects of ISGs and the positive feedback loop via IRF7, type I IFN signaling also induces the production of a range of cytokines and chemokines, pro-and antiapoptotic factors, and affects multiple other signaling pathways. Through modulation of the differentiation and function of dendritic cells, T cells, natural killer cells, and B cells, type I IFNs shape the antiviral immune response beyond the initial innate immune response . Title: Type I Interferon Response Is Delayed in Human Astrovirus Infections", "Passage: Expression of ISG56 mRNA accumulated in cells treated with exogenous IFN and polyI:Ctransfected cells starting at 12 h . Detection of ISG56 mRNA in HAstV-infected cells at 24 hpi could indicate that IFN-\u03b2 had already been released to the extracellular media, although it has also been described that some viruses from diverse families can induce synthesis of ISG56 mRNA in the absence of both IFN production and/or virus replication . Title: Type I Interferon Response Is Delayed in Human Astrovirus Infections\nPassage: analysis. Title: Type I Interferon Response Is Delayed in Human Astrovirus Infections\nPassage: and the potential role of nsP1a/4 protein as an antiviral target.", "Title: Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions\nPassage: The damage of the epithelial cells promotes streptococcal infection in different ways. It results in the loss of their barrier function and allows the bacteria to get access to deeper areas of the epithelium that are usually not exposed to the environment. This conclusion is supported by our infection studies with PCLS, another culture system for differentiated airway epithelial cells 37 . It has been suggested that dead cells may provide a rich source of nutrition and growth factors and thus enhance streptococcal growth 48 . We found larger numbers of bacteria in areas where the epithelium had been damaged. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: On the other end of the spectrum, viruses that induce strong type 1 inflammation and cell death such as IFV and certain CoV , may not cause prolonged inflammation due to strong induction of antiviral clearance. These infections, however, cause massive damage and cell death to the epithelial barrier, so much so that areas of the epithelium may be completely absent post infection . Factors such as RANTES and CXCL10, which recruit immune cells to induce apoptosis, are strongly induced from IFV infected epithelium . Additionally, necroptotic factors such as RIP3 further compounds the cell deaths in IFV infected epithelium Title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications", "Passage: as well. This is apparent with the clear enrichment of the pathways of apoptosis, mitochondrial apoptotic processes, and necroptosis that contribute to cell death and mechanical barrier loss during infection . Genes such as IFI6, BAK1, CAPS8, TNFSF10, and FAS suggest active apoptotic cell death that not only destroys cells in the epithelial barrier, but may also serve to propagate the virus and to perpetuate the damage . Furthermore, during virus infection, aberrant regulation of apoptosis may also lead to further injury to the epithelium and surrounding tissues . On the other hand, necroptosis pathways have also been observed to Title: Port d\u2019Entr\u00e9e for Respiratory Infections \u2013 Does the Influenza A Virus Pave the Way for Bacteria?", "Passage: extrinsic apoptotic pathway via production of inflammatory cytokines, resulting in apoptosis or even necrosis of the epithelium . Furthermore, aberrant coagulation induced by virus infection causes a hyper-inflammatory response . All these events contribute to lung tissue injury . The epithelial damage due to viral replication provides a beneficial environment for initial bacterial attachment . On the other hand, already colonized bacteria might enhance influenza virus virulence either by directly secreting proteases that cleave and activate HA or, indirectly, by activating host proteases such as plasminogen, which increases replication rates and infectivity of the virus .", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: Trafficking of N for viral assembly: Classically, N protein in infected cells appears to be clustered or particulate in nature, with a heavy concentration at a single perinuclear location, widely considered to be the Golgi . The N proteins of hantaviruses are found in association with particulate fractions, and confocal microscopy and biochemical-inhibitor studies have shown that N tracks along microtubules but not with actin filaments . The ultimate destination for N, for its assembly into viral particles is the Golgi, and it traffics there via the endoplasmic reticulum-Golgi intermediate complex , also known as vesicular-tubular cluster . A dominant Title: Vaccine Potential of Nipah Virus-Like Particles", "Passage: been identified as the NiV entry receptors . After fusion of the virus and the cell membrane, the viral ribonucleoprotein is released in to the cell cytoplasm. Following transcription and replication, the viral components migrate to the plasma membrane for assembly and budding of progeny particles . Title: The intrinsically disordered C\u2010terminal domain of the measles virus nucleoprotein interacts with the C\u2010terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded\nPassage: both monomeric and assembled forms of N . Figure 1 shows a schematic representation of the MV N NUC -P complex, which highlights the role of N TAIL in the recruitment of P via the binding to XD. Title: The lifecycle of the Ebola virus in host cells", "Passage: As VP40 has many different locations within host cells, including the inclusions, late endosome, nucleocapsids, and MVBs. It is thought that VP40 may be transported to the site of budding either associated with nucleocapsid structures or with cellular membranes . For example, VP40 is accumulated in the late endosome in high amounts for oligomerization and the formation of the regular arrays The molecular mechanism of RNP and the mechanism by which VP35 releases RNA from RNP remain unknown. Assembly and budding: Assembly is initiated by the nucleocapsids which accumulate in the perinuclear region, and are then transported to the budding", "Title: Neonatal Genetic Delivery of Anti-Respiratory Syncytial Virus (RSV) Antibody by Non-Human Primate-Based Adenoviral Vector to Provide Protection against RSV\nPassage: Respiratory syncytial virus is one of the leading causes of lower respiratory tract infections in children, with a high morbidity and mortality, especially in developing countries . Most children are infected during their first year of life, and infants under six months of age are at highest risk for severe disease, especially those with bronchopulmonary dysplasia or cyanotic heart disease . Title: Dichloro-Phenyl-Benzotriazoles: A New Selective Class of Human Respiratory Syncytial Virus Entry Inhibitors", "Passage: Viral pneumonia is an increasing health problem worldwide, and the incidence and number of viruses known to induce respiratory diseases have expanded in recent years . Human Respiratory Syncytial Virus is the main etiological agent of pneumonia, bronchiolitis, and lower respiratory tract infections . In particular, RSV is the leading cause of acute LRTIs in children less than 5 years of age , and the responsible for substantial disease burden in the elderly, similar to that of non-pandemic influenza A . Every year, this pathogen causes 30 million LRTIs and the annual death toll from RSV-related diseases is now \u223c Title: Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene", "Passage: were carried out in \"accordance\" with the approved guidelines. Demographic data -including age, sex, race and ethnicity -were recorded at the time of enrollment. Singleplex qRT-PCR assays for multiple viruses, including, RSV, human rhinovirus, human enterovirus, and human ribonuclease P in nasal washes were performed according to standardized protocols 25, 33, 34 , and are described previously 25 . The algorithm used to select samples included all samples with a doctor diagnosis of bronchiolitis, plus, illnesses from the lower end of the severity spectrum based on an ordinal severity score 35 with an RSV cycle threshold greater than 20. This Title: Respiratory syncytial virus evaluation among asymptomatic and symptomatic subjects in a university hospital in Sao Paulo, Brazil, in the period of 2009\u20102013", "Passage: Human respira t ory syncytial virus is considered an important viral agent causing u pper respiratory and lower respiratory tract infection, especial l y in children, the elderly, and immunocompromised adults. Some studies have also shown the importance of RSV as a causative agent of respiratory tract infections in healthy adults, causing significant morbidity. 15 Studies of RSV epidemiology in healthy individuals are uncommon, and the risks of RSV transmission from infected children to other individuals are ba rely known. 2 The positivity for RSV among the studied populations varied within and between symptomatic and asymptomatic groups. The RSV detection", "Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections\nPassage: Five surveys used an online respondent-driven method, which can be considered as a snowball or chain sampling technique. 31, 45, 60 Only one survey did not state information on sampling techniques. 34 Finally, three surveys conducted at the general population level used a convenience sample, 29, 44, 50 therefore not relying on a sampling frame. More details on the distribution of sampling schemes based on time and regions are presented in eFigure 3; http://links.lww.com/EDE/B552. Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: Approximately half of the surveys employed convenience sampling, in which subjects were selected based on their convenient accessibility to researchers. 57 This sampling technique was also used for the sake of comparing data collection tools, 18, 49, 50, 56, 58 data collection methods, 59 or study designs. 10, 17, 50 Seven surveys used random sampling. 5, 26, 28, 34, 35, 51 Among these studies, only two surveys were considered representative of the entire country, 26, 28 and the remaining surveys were representative of a region 34, 35 or a city or town. 5, 51 Three surveys employed multi-stage sampling, 15, Title: Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database", "Passage: away from hospitals . The subjects for this investigation were randomly selected and unfiltered. The time period of each group was consistent and was evenly distributed in two weeks. We made further inquiries 189 amicable interviewees who were willing to take the SMP tests about their background, as well as the privacy protection in SMP data. The patients were fully informed before the voluntary agreements for SMP tests were signed. The researchers obtained the respective remaining samples from nurses after the ordinary blood tests were performed. No extra sampling of blood was performed in this study. Title: Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households", "Passage: Randomization lists were prepared by a biostatistician . Eligible study participants were randomly allocated to three groups. The first 100 households were randomized in the ratio 2:1:1 and subsequent households were randomized in the ratio 8:1:1 using a random number generator . The rationale for changing the randomization ratio was to allow us to gather maximum information about the natural characteristics of influenza transmission in households in the absence of control measures, after evaluating the feasibility of each of the interventions in at least 25 households. Interventions were assigned to households by the study manager based on the randomization sequence.", "Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model\nPassage: One approach for a broad antiviral therapy is the creation of a protective physical barrier in the nasal cavity using carrageenan. Carrageenan is a high molecular weight sulfated polymer derived from red seaweed that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA ). Three main forms of carrageenans are commercially used: kappa, iota and lambda. They differ from each other in the degree of sulfation, solubility and gelling properties . The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Kappa-carrageenan and iota-carrageenan were purchased from FMC Biopolymers . The identity, purity of carrageenan subtypes and the molecular weight was confirmed by NMR analysis as described elsewhere and the presence of lambda-carrageenan was below the detection limit of 3%. The dry polymer powders were dissolved in aqua bidest to a final concentration of 2.4 mg/ml iota-and 0.8 mg/ml kappa-carrageenan. This 2x stock solution was sterile filtered through a 0.22 \u03bcm filter and stored at room temperature until use. For further testing the stock solution was diluted to a mixture containing 1.2 mg/ml iota-carrageenan and 0.4 mg/ml kappa-carrageenan . Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: Abstract: BACKGROUND: Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo. PRINCIPAL FINDINGS: We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains pdm, H3N2, H5N1, Title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model", "Passage: During the evaluation process we found that the binding efficiency of different carrageenan subtypes on different influenza strains varies. The combined use of iota-and kappa-carrageenan for the treatment of lethally influenza infected C57Bl/6 mice revealed a better therapeutic effect than the use of iota-carrageenan alone . Thus, to provide a broader spectrum of activity against different influenza virus strains, a mixture of iota-and kappa-carrageenan was used for further evaluation.", "Title: Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database\nPassage: medical databases were also helpful to the public health professionals . Title: Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database", "Passage: Various biomedical databases have already been constructed worldwide, such as Human Genome Database , Recon 2, DrugBank, Human Metabolome Database, and ClinicalTrials . Most of these databases are open to researchers free of charge. The prominent development of bioinformatics depends on the availability of biomedical databases. However, the existing databases mainly focus on laboratory studies instead of clinical studies. The completion and maintenance of these databases mainly depend on research funds from the government. Therefore, the current biomedical databases are still far from clinical auxiliary diagnoses. Few clinical databases have been established, such as ClinicalTrials, which currently lists 144,133 studies Title: Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review", "Passage: Overall, all but one of the meta-analyses reported the search of at least 1 electronic database and 147 reported the search of > 2 electronic databases. One third provided the search strategy for each database . MEDLINE, Embase, and the Cochrane Library were most frequently searched , 149 , and 126 meta-analyses, respectively). In addition to the search of electronic databases, 162 meta-analyses reported screening the reference lists of included studies, and 12 reported hand-searching journals. About one-third of the meta-analyses reported searching for grey literature: 41 conference abstracts, 33 registries, and 15 contacted experts. For 82 meta-analyses , the Title: Database resources of the National Center for Biotechnology Information\nPassage: The PubMed database contains citations from life science journals, many of which include abstracts and links to their full text articles.", "Title: Participant retention practices in longitudinal clinical research studies with high retention rates\nPassage: Of the 19 participating studies, 13 were prospective cohort studies, 5 were RCTs, and 1 was a quasiexperimental study . Included studies had diverse patient populations, including victims of intimate partner violence, persons living with human immunodeficiency virus and acquired immunodeficiency syndrome , survivors of critical illness and other serious illnesses. The target sample size for studies ranged from 255-10,000. Actual sample recruitment at the time of interview ranged from 205 for the Community Aging in Place -Advancing Better Living for Elders study with older adults aging in place to 2528 for the Alzheimer's Disease Anti-Inflammatory Prevention Trial . Though Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: The prospective design is subject to less recall bias than the retrospective design. This notion can be partly explained by the fact that respondents in the former are informed in advance about which days they will be assigned for reporting their contact information. Furthermore, they are also asked to keep a diary with them and finish reporting before the surveying day is elapsed. Thus, the prospective design requires more commitment from respondents. In return, a prospective design can obtain more reported contacts compared with retrospective design. 17, 50 However, large-scale studies are needed to further confirm these conclusions. Title: A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections", "Passage: By prospective design, we mean that respondents are informed in advance of the day that they are requested to record their contacts. 6, 17, 32 In a retrospective design, respondents recall their contacts over a past time period without prior warning or instruction that they would be requested to do so. Of 64 surveys, 29 used a retrospective design and 26 used a prospective design. Only four surveys 6%) used both designs for the purpose of comparison. 10, 17, 50 For five surveys , it was not completely clear whether the study was prospective or retrospective. 20, 24, 30, 48 Title: Mortality, morbidity and health in developed societies: a review of data sources", "Passage: In a context of population ageing, some specific longitudinal surveys have been implemented for monitoring functional or cognitive limitations and dependency in the older population. For example, the Longitudinal Aging Study Amsterdam has studied physical, emotional, cognitive and social functioning in late life, the connections between these aspects and the changes that occur in the course of time . It started in 1992 and is based on a nationally representative sample of older adults in private households aged 55 years and over. 14 Three birth cohorts are followed in successive waves every 2 or 3 years. Each wave has three", "Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult. Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Community responses to communication campaigns for influenza A (H1N1): a focus group study", "Passage: Any conclusions drawn from this study should be considered tentative as the findings cannot be generalised to the population at large. It is not known whether the individuals who chose to participate differed from those who were eligible but chose not to participate. Whilst this study intentionally involved participants with diverse cultural and ethnic backgrounds, and included individuals from vulnerable groups, the sample does not permit conclusions regarding the effect of socio-demographic factors such as age or gender. Further research is needed to explore the complexities involved in the way in which the framing of risk messages impacts on people's Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations", "Title: Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy\nPassage: in vitro labeling using cell-permeant fluorescent dyes, cells are adoptively transferred by intravenous injection into mice for intravital microscopy. However, pulsed labeling of cells with vital dyes in vitro has limitations for certain MP-IVM studies including long-term imaging. Dye leakage, bleaching or extensive cell division of labeled cells over time results in the dilution of functional cytoplasmic dyes with a significant reduction in the signal-to-noise ratio. Consequently, imaging of subcellular structures with little cytoplasm such as cell protrusions might not be visible by MP-IVM although cell tracking is still possible. Alternatively, cells can be isolated from knock-in mice that ubiquitously Title: Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine", "Passage: in the same shading. Title: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case\nPassage: counter-stained by 2% nuclear quick red solution for 30 s. For each tissue, double-labeled stain with IHC and ISH was repeated three times for data analysis. To strengthen further the results of colocalization studies, we performed ISH and IHC on consecutive sections. Tissue sections showing ISH-positive cells were carefully compared with consecutive tissue sections on which IHC with antibodies against specific cell markers was applied. Co-localization of a specific cellular marker and viral genome was clearly identified. Title: Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone", "Passage: Radiolabeled antibodies were prepared as detailed above, and injectate was assayed using a well counter with a calibration factor of 517, as determined previously. 29 In a volume of 150 \u00b5L, 225 \u00b5Ci of radiolabeled antibody was administered intravenously via the retro-orbital sinus. Mice were serially scanned on days 1, 3, 5, and 7 on a microPET R4 system followed by Faxitron MX-20-DC12 digital X-ray imaging system .", "Title: Estimating the number of infections and the impact of non-\nPassage: modelled deaths are informed by an infection-to-onset distribution (time from infection to the onset Title: Estimating the number of infections and the impact of non-\nPassage: infection-to-onset distribution is Gamma distributed with mean 5.1 days and coefficient of variation Title: Networks and the Epidemiology of Infectious Disease", "Passage: where w is the probability density function for the generation interval t j \u2212 t i , that is, the time between infector i's infection time and infectee j's infection time. Of course, infection times are never observed in practice so symptom onset times are used as a proxy, with the assumption that the distribution of infection time to symptom onset time is the same for every individual. Bayesian methods are used to infer \"late-onset\" cases from known \"early-onset\" cases, but large uncertainty of course remains when inferring the reproductive ratio close to the current time as there exists large Title: Estimating the number of infections and the impact of non-\nPassage: infection, onset of symptoms and outcome.", "Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease\nPassage: Improved access to health care, better nutrition and improved living conditions might contribute to further decreases in childhood pneumonia burden. The WHO Integrated Global Action Plan for diarrhea and pneumonia highlights many opportunities to protect, prevent and treat children . Breastfeeding rates can be improved by programs that combine education and counseling interventions in homes, communities and health facilities, and by promotion of baby-friendly hospitals . Improved home ventilation, cleaner cooking fuels and reduction in exposure to cigarette smoke are essential interventions to reduce the incidence and severity of pneumonia . Prevention of pediatric HIV is possible by providing interventions Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: . Pneumonia deaths decreased from 1.8 million in 2000 to 900,000 in 2013 . These data do not reflect the full impact of increasingly widespread use of pneumococcal conjugate vaccine in low-and middle-income countries because the incidence of pneumonia and number of deaths are likely to decrease still further as a result of this widespread intervention . Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The overall burden of childhood pneumonia has been reduced substantially over the last decade, despite an increase in the global childhood population from 605 million in 2000 to 664 million in 2015 . Recent data suggest that there has been a 25% decrease in the incidence of pneumonia, from 0.29 episodes per child year in low-and middle-income countries in 2000, to 0.22 episodes per child year in 2010 . This is substantiated by a 58% decrease in pneumonia-associated disability-adjusted life years between 1990 and 2013, from 186 million to 78 million as estimated in the Global Burden of Disease study Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: per million between 1981 and 1998, to 66 per million in 2005 . These trends have been reversed since the introduction of pneumococcal conjugate vaccination-13. Data from the United States suggest that empyema decreased by 50% in children younger than 5 years ; similarly, data from the United Kingdom and Scotland showed substantial reduction in pediatric empyema following pneumococcal conjugate vaccination-13 introduction .", "Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland\nPassage: The length of the region from the p4.7 to p12.7 genes in the two viruses was 544 base pairs. Compared with NC99, Irish ECoVs, had a total of 37 nucleotide deletions within p4.7 and the non-coding region following the p4.7 gene. Compared with Obihiro 12-1 and 12-2, Irish ECoVs had a three-nucleotide insertion. When compared with Tokachi09, the Irish ECoVs had a 148-nucleotide insertion . The p12.7 gene of the two Irish ECoVs did not have deletions or insertions, and the nucleotide identities were 98.8-99.7% between these viruses and the other ECoVs . Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: The nucleotide sequences of the complete N gene, the partial S gene and the region from the p4.7 to p12.7 genes of two positive samples were determined. The nucleotide identities of the N and S genes of the two Irish ECoVs were 99.8% and 99.5% , respectively. The nucleotide identities of the N gene of the two Irish ECoVs and the ECoVs from other continents are summarised in Table 2 . Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: Although ECoV has been identified on three continents, little is known about the genetic and pathogenic diversity in field viruses. In this study, sequence and phylogenetic analysis demonstrated a high level of homology between viruses detected in a donkey and a horse in two provinces in Ireland in different years. This suggests that Irish ECoVs may have low genetic diversity. Compared with the ECoVs of other countries, the N, S and p12.7 genes of the two Irish viruses were highly conserved. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions . Title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland", "Passage: Phylogenetic analysis was performed for the nucleotide sequences of the complete N and partial S genes . The analysis for the N gene showed that Irish ECoVs were independently clustered although they were closely related to Japanese viruses identified after 2009. In the phylogenetic tree of the S gene, Irish ECoVs were closely related to all other ECoVs analysed.", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: up'' and translates in Swahili to ''the illness of the bended walker'' . In Africa, CHIKV is maintained in a sylvatic cycle among forest-dwelling Aedes spp. mosquitoes, wild primates, squirrels, birds, and rodents . In Asia, the disease is vectored by Ae. aegypti and Ae. albopictus . Transmission in Asia occurs in an urban cycle whereby the mosquito spreads the disease from an infected human to an uninfected human, following an epidemiological pattern similar to dengue fever . Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: Text: Chikungunya virus , a mosquito-borne pathogen listed by National Institute of Allergy and Infectious Diseases as a Category C Priority Pathogen that causes Chikungunya fever , has been spreading throughout Asia, Africa, and parts of Europe in recent times . CHIKV is an arthropod-borne virus and is transmitted to humans primarily by Aedes aegypti, the infamous yellow fever propagator . CHIKV infection is marked by severe joint pain, contorting its victims into unusual postures . The disease gets its name from the Kimakonde vernacular language of Tanzania and Mozambique, and the word chikungunya means ''that which contorts or bends Title: Evaluation of the Antiviral Potential of Halogenated Dihydrorugosaflavonoids and Molecular Modeling with nsP3 Protein of Chikungunya Virus (CHIKV)", "Passage: continent of Asia and various parts of the world. The name chikungunya originates from \"Makonde\", meaning \"to become twisted\". It denotes the \"curved\" appearance of those going through joint ache as a result of chikungunya infection. Chikungunya virus spreads by mosquito vectors Aedes aegypti and Aedes albopictus. The common eukaryotic hosts are primates and humans. In humans, the symptoms associated with CHIKV are nausea, fever, joint pain, vomiting, rashes, and persistent arthralgia. Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: vector similar to the ones observed in Reunion Island .", "Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: On May 12, 2015, a case of Ebola in a male Italian volunteer HCW was reported. He returned from Sierra Leone on May 7, became symptomatic on May 10, and hospitalized on May 11. No inflight contact tracing was done. There were 19 contacts to this case . On July 20, 2015, Italy was declared Ebola-free having no additional EVD cases and no deaths . Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak\nPassage: . By March 29, 2016 , there were 3811 EVD cases, 2543 deaths and 187 cases among health care workers , of which 94 died . Title: Ebola virus disease and critical illness", "Passage: The West African EVD outbreak was first recognized in March 2014 in the forested region of southeastern Guinea. However, the first EVD case may have happened as early as December 2013 with zoonotic transmission of EBOV from an animal to a human, and subsequent human-to-human spread . Transmission was likely well underway throughout West Africa in the spring of 2014 . By June 2014 there were a few hundred confirmed or probable EVD cases, 3000 by the end of August-outstripping the ability of providers at existing Ebola treatment units to isolate and care for patients-and eventually over 20,000 cases by Title: Managing emerging transnational public health security threats: lessons learned from the 2014 West African Ebola outbreak", "Passage: Health officials in Mali investigated six suspect cases in April 2014 which helped prepare for the introduction of their first confirmed case in October 2014. This EVD case was a two-year-old female from Guinea . Being symptomatic during her journey to Mali, the girl died the following day. On October 25, a Grand Imam from Siguiri prefecture in Guinea was admitted to a clinic in Bamako for acute kidney failure. Ebola was not initially recognized and he died on October 27. Because his symptoms began in Guinea, he is reported as a Guinean case. That case led to seven additional", "Title: Hepatitis B Virus Genotype G forms core-like particles with unique structural properties\nPassage: The HBV capsid plays an important role in envelopment of the virion with membrane containing the HBsAg, which is a prerequisite for the secretion of viable progeny virions . Amino acids in the core protein that are involved in envelopment competence, and which presumably make important contacts with the cytoplasmic domain of membrane-bound preS1 protein, have been mapped, both by mutagenesis and by analysis of naturally occurring patient-derived HBV mutants that vary in their capacities to secrete mature virions . There are thus 11 residues that have been shown to be essential for envelopment but were nonessential for capsid formation. Title: One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor", "Passage: HBV envelope protein, namely the surface antigens, plays an essential role in the infection process. Both genetic and functional examination identified one domain in the Nterminus of HBV preS1 necessary for infection. This domain has been shown to function as a direct mediator for HBV by binding presumably cellular corresponding receptor . More importantly, the myristoylated peptide is shown to effectively block HBV infection in primary human hepatocytes and in the human hepatocytechimera mouse at a nanomolar concentration . In fact, a clinical trial testing the efficacy of this peptide in preventing HBV infection has been ongoing . Clearly, this Title: Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis", "Passage: Our understanding of the E2 protein has been enhanced by the recent crystallization of the E2 core domain , providing evidence that refutes the previous hypothesis of E2 as a class II fusion protein . Canonical class II fusion proteins consist of three protein domains with an elongated structure in which domain 2 harbors the fusion peptide that is embedded within the dimer interfaces ). In contrast, E2 is globular in shape with the E2c adopting a compact architecture surrounded by disordered variable loops. E2c consists of a central Ig-like \u03b2-sandwich scaffold flanked by front and back layers of protein Title: Hepatitis B Virus Genotype G forms core-like particles with unique structural properties", "Passage: N-terminal insertion peptide of HBV/G . It is tempting to speculate that the 12 amino acid N-terminal insertion in HBV/G could be responsible for partially reducing the efficient envelopment of HBV/G, because of its proximity to several of these key residues that make contacts with the cytoplasmic domain of HBsAg. In particular, the N-terminal insertion partially covers several of these residues that were shown to be involved in secretion of mature particles, notably S17, F18, L60 and L95 and thus might sterically hinder interactions between the L protein and core particle of HBV/G during envelopment. In addition, in previously published", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Abstract: The first known cases of Middle East respiratory syndrome , associated with infection by a novel coronavirus , occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia . Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels . MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Two studies during 2015, one looking at Jeddah-2014 MERS-CoV variants and another looking at a variant exported from South Korea to China, have now identified signs of genetic recombination among MERS-CoV variants. While human and camel whole genome sequences have retained >99 % identity with each other, members of genetically distinct lineages can and do swap genetic material when suitable conditions and coinfections co-occur . Shared identity implies that the major source for human acquisition is the DC, rather than another animal, although more testing of other animal species is needed to confirm that conclusion. Over a month, a DC Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: Genome sequence located to a distinct clade were identified from an Egyptian DC that was probably imported from Sudan. This does not fit into either of the current clades . A virus sequenced from a Neoromicia capensis bat was more closely related to MERS-CoV than other large bat-derived sequences had been to that point, but the genome of a variant of a MERS-CoV has yet to be discovered and deduced from any bat . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: mortality. It remains unclear if this group are uniquely affected by MERS-CoV or if other respiratory virus infections, including those from HCoVs, produce a similarly serious impact. In South Korea, a single imported case created an outbreak of 185 cases and 36 deaths that had a disproportionate impact on economic performance, community behaviour and trust in government and the health care system. Household human-to human transmission occurs but is also limited. Educational programs will be essential tools for combatting the spread of MERS-CoV both within urban and regional communities and for the health care setting.", "Title: Host resilience to emerging coronaviruses\nPassage: REviEW Jamieson future science group Risk factors for SARS-CoV patients included an older age and male . Immune factors that increased mortality for SARS-CoV were a higher neutrophil count and low T-cell counts . One factor that increased disease for patients infected with SARS-CoV and MERS-CoV was infection with other viruses or bacteria . This is similar to what is seen with many other respiratory infections. A recent study looking at malaria infections in animal models and human patients demonstrated that resilient hosts can be predicted . Clinical studies have started to correlate specific biomarkers with disease outcomes in ARDS Title: Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses", "Passage: None of these studies examined the causal factors that lead to the higher influenza mortality in the high-risk groups described. It is clear that multiple converging risks account for the high rates of complications, including socioeconomic factors such as inability to access care, delayed seeking of care, higher rates of poverty, and greater numbers of household members. A few of the risk factors listed in the previous sections, however, share a degree of immune system impairment. One can, therefore, speculate that the partial protection afforded by the immune system, primarily by cross-reactive CD8+ T-cells recognizing viral epitopes, is decreased in Title: Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses", "Passage: concordance with the high serum levels of IL-6 and IL-10 in the group dependant on mechanical ventilation. The authors concluded that severe disease is associated with an impaired transition from innate to adaptive immunity in response to the pH1N1 virus, similar to observations in the context of SARS and severe infections caused by H5N1. The impaired adaptive response was also associated with delayed viral clearance. This study did not, however, explore the role of genetic polymorphisms in this immune dysregulation. Title: Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses\nPassage: these effects appear to be related to the kinetics and strength of macrophage recruitment to the lung . In vitro evidence further suggests upregulation of CCR5 on monocyte-derived macrophages that may enhance pathogenesis .", "Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1\nPassage: Beside DC-SIGNR, other HIV-1 receptors are known to influence MTCT of HIV-1 ). Genetic variants in CCR5 have been shown to influence vertical transmission of HIV-1. CCR5 promoter variants resulting in higher expression of the receptor were associated with increased risk of MTCT of HIV-1 among sub-Saharan Africans . The 32-pb deletion polymorphism in CCR5 has be shown to protect from vertical transmission of HIV-1 , but this variant is virtually absent among African populations . High copy numbers of CCL3L1, a potent HIV-1 suppressive ligand for CCR5, are associated with higher chemokine production and lower risk of MTCT of Title: Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission", "Passage: Genetic variations in HIV-1 co-receptors and determinants of immunity have been shown to influence the outcome of MTCT of HIV-1 . Variants that result in either increased CCR5 expression or a non-functional receptor influenced risk of vertical transmission . The CCR5 32 base-pair deletion is absent in African populations . Genetic polymorphism of innate immunity determinants such as toll-like receptor 9 and mannose-binding protein also increased the risk of MTCT . Discordance at the human leucocyte antigen class I loci between mother and child or specific HLA alleles also protect against MTCT . Title: Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1", "Passage: Text: Without specific interventions, the rate of HIV-1 mother-tochild transmission is approximately 15-45% . UNAIDS estimates that last year alone, more than 400,000 children were infected worldwide, mostly through MTCT and 90% of them lived in sub-Saharan Africa. In the most heavilyaffected countries, such as Zimbabwe, HIV-1 is responsible for one third of all deaths among children under the age of five. MTCT of HIV-1 can occur during pregnancy , delivery or breastfeeding . High maternal viral load, low CD4 cells count, vaginal delivery, low gestational age have all been identified as independent factors associated with MTCT of HIV-1 . Title: Neutrophils Turn Plasma Proteins into Weapons against HIV-1", "Passage: Structural rearrangements within gp120 allow the binding to co-receptors of the chemokine-receptor family, which aids in virus entry. HIV-1 uses two important co-receptors. The chemokine receptor CCR5 is the co-receptor utilized by macrophage-or Mtropic viruses. They are referred to as R5 viruses . The chemokine receptor CXCR4 is the co-receptor for T-tropic or X4 viruses . It is especially used by viruses appearing later in HIV-1 infection . Dual-tropic HIV-1 strains use both co-receptors .", "Title: Requirement of CRTC1 coactivator for hepatitis B virus transcription\nPassage: Hepatitis B virus , a member in the family of Hepadnaviridae, has a DNA genome 3.2 kb in size which is partially double stranded. Over 350 million people are chronically infected with HBV worldwide, including \u223c10% of the population in Hong Kong and China, 15-40% of whom will terminally develop severe liver diseases including hepatocellular carcinoma . Although multiple factors are involved in the development of HCC in HBV carriers, high level of HBV DNA has been identified as a major risk . Title: One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor", "Passage: Text: Among the five hepatotropic hepatitis viruses, only hepatitis B virus and its satellite hepatitis D virus still wait for the development of an in vitro infection system in cell culture. One hepatocellular carcinoma cell line, HepaRG, can be infected at a modest efficiency after weeks of culture and induced differentiation . Even primary human hepatocytes rapidly lose the capacity for HBV infection after brief cell culture. The HBV infection demands both intracellular and cell-surface factors. The intracellular requirements appear less stringent, as after transfection of HBV DNA into many HCC cell lines or mouse liver, which cannot be infected Title: Requirement of CRTC1 coactivator for hepatitis B virus transcription", "Passage: HepG2.2.15 cells were cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal calf serum, 2 mM L-glutamine and 380 g/ml G418. Plasmid DNA was transfected into HepG2 cells using GeneJuice transfection reagent . siRNA was transfected into HepG2 and HepG2.2.15 cells using Lipofectamine 2000 . Title: Requirement of CRTC1 coactivator for hepatitis B virus transcription\nPassage: declined in a dosedependent manner in these cells .", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: lifestyle from autonomous bacteria to endosymbionts. This transition is often considered as extremely rare and a hallmark of evolution of life on our planet. However, there are many other obligate intracellular parasites such as Rickettsia, Chlamydia trachomatis, Coxiella burnetii , Mycobacterium leprae, M. tuberculosis, and M. mycoides . Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: The change of lifestyle of the endosymbionts in the two cases of mitochondria and chloroplasts is striking. Both of them drastically reduced their genetic make-up. Mitochondria contain less than 37 genes, left from the original about 3,000 genes. Is endogenization of retroviruses, the ERVs, which are integrated into germline cells, related to endosymbiosis? Are these endosymbionts models for the transition from autonomous lifestyle to a parasitic life-which may have taken place with viruses? A more recent typical example for a reductive evolution are Rickettsia. These bacteria were assumed for some time to be viruses because of their obligatory intracellular parasitic Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: existence. Rickettsia have evolved from autonomously replicating bacteria. Reductive evolution of endosymbionts can yield bacteria with tiny genomes on the expense of autonomous extracellular life. Their genomes are 1.11 mio bp in length with about 834 protein-coding genes, and loss of 24% by reductive evolution . Rickettsia may have some relationship with cyanobacteria, which are considered as the major symbionts. Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: have given up their autonomous replication and became parasites -as has been described for some bacteria .", "Title: Estimating the number of infections and the impact of non-\nPassage: as isolation if travelling back from an epidemic country such as China. Title: Travel Patterns in China\nPassage: 10,000 individuals were selected each from the administrative areas of Huangshan city in Anhui province and Shenzhen city in Guangdong province. Title: Spatiotemporal Analysis of Influenza in China, 2005\u20132018\nPassage: A rapid increase in the numbers of airlines and high-speed railway transports in China has been reported in recent years 56 . These factors would make it easy to transmit the influenza virus at a larger scale and in a shorter time across the country 56-58 . Title: Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus", "Passage: Population data were extracted from the International Database , U.S. Census Bureau . The individual probability of travel for each country was calculated as the daily travel rate divided by the population size. The arrival data were extracted from visitor arrival statistics provided by the Hong Kong Tourism Board . These statistics include the total number of arrivals by country, together with their modes of transport. Forty-four countries, collectively contributing more than 95% of annual arrivals to Hong Kong, were selected for the analysis . The yearly frequency of departing Hong Kong residents by different transport modes were collected from", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: In 2015 two large outbreaks occurred. South Korea was the site of the first large scale outbreak outside the Arabian Peninsula and produced the first cases in both South Korea and China, occurring between May and July 2015. This was closely followed by a distinct outbreak in Ar Riyad province in the KSA which appeared to come under control in early November. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: In humans, overt disease was given the name Middle East respiratory syndrome, with the acronym MERS. From intermittent animal-to-human spill-over events, the MERS-CoV spreads sporadically among people, causing more severe disease among older adults, especially males, with pre-existing diseases. The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: mortality. It remains unclear if this group are uniquely affected by MERS-CoV or if other respiratory virus infections, including those from HCoVs, produce a similarly serious impact. In South Korea, a single imported case created an outbreak of 185 cases and 36 deaths that had a disproportionate impact on economic performance, community behaviour and trust in government and the health care system. Household human-to human transmission occurs but is also limited. Educational programs will be essential tools for combatting the spread of MERS-CoV both within urban and regional communities and for the health care setting. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: MERS and SARS have some clinical similarities but they also diverge significantly . Defining characteristics include the higher PFC among MERS cases and the higher association between fatal MERS and older males with underlying comorbidities. For the viruses, MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV.", "Title: Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies\nPassage: temperatures of \u221220 \u2218 C , +4 \u2218 C , and room temperature and by subjecting the pseudotype virus to multiple freeze-thaw cycles. The initial titre of the H5 lacZ pseudotype was 4.3 \u00d7 10 5 IFU/mL and >80% infectivity remained after five cycles of freeze-thaw . In parallel, pseudotypes bearing rabies CVS-11 and HIV-1 envelope glycoproteins were subjected to the same freeze-thaw regimen and were found to lose approximately 4% and 9% activity, respectively, per freeze-thaw cycle . In relation to temperature storage variations and their effect on pseudotype viability, Figure 3 shows that H5 A/Viet Nam/1194/2004 HA pseudotypes Title: Virus-Vectored Influenza Virus Vaccines", "Passage: in humans . Currently, NA-specific antibody responses are not considered a correlate of protection . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx . LAIV immunization induces serum antibody responses, mucosal antibody responses , and T cell responses. While robust serum antibody and nasal wash antibody responses are associated with protection from infection, other immune responses, such as Title: Viral vector-based influenza vaccines", "Passage: the choice of a viral backbone of cold-adapted viruses and are therefore temperature-sensitive and replicate only locally after administration at the mucosa of the nasopharynx. 2 In addition to serum antibodies, immunization with LAIV also induces mucosal antibodies and cytotoxic T-lymphocytes . Title: Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine", "Passage: The human LAIV used in the US was generated by the adaptation of an IAV to growth at suboptimal decreasing temperatures during multiple passages in primary chicken kidney tissue culture cells . During this ts adaptation process, A/Ann Arbor/6/60 H2N2 gained multiple mutations in the viral genome, which are responsible of the ts and cold-adapted phenotype that allow the virus to grow efficiently at low temperatures. However, viral replication is restricted at higher temperatures, which are found in the human lower respiratory tract or during febrile process , resulting in an attenuated phenotype . This allows the host to mount", "Title: Viral factors in influenza pandemic risk assessment\nPassage: 5. Finally, the infection must spread beyond the local area to infect members of distant populations, a process accelerated by modern global travel . This step and the one before are enhanced if the level of population susceptibility is high, as occurs when the surface proteins of the new strain are dissimilar to those on any currently or recently circulating human influenza A strains. Title: Viral factors in influenza pandemic risk assessment\nPassage: improving our risk assessment capacity and developing responses robust to the possibility that we will once again be caught by surprise. Title: Viral factors in influenza pandemic risk assessment\nPassage: pandemic. Title: A systematic review of studies on forecasting the dynamics of influenza outbreaks", "Passage: The number of new infections at any time during an influenza outbreak depends on several biological, behavioral, and environmental factors that influence the transmission of influenza viruses. 22 These factors include immunity, virulence factors, contact type and patterns, and climatic conditions that influence viral survival. The inclusion of these parameters in models for influenza forecasting could improve forecast accuracy. However, in addition to the difficulty of estimating true influenza incidence from laboratory confirmed cases and ILI, estimating transmission and severity parameters during pandemics remains a challenge. 23 We discuss these challenges.", "Title: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey\nPassage: In Argentina , the case-fatality rate of influenza A/ H1N1v infected children was 5%, with a global pediatric mortality rate 10 times greater compared to previous flu seasons. National surveys in the United Kingdom and U.S reported also a higher influenza related mortality rate during the pandemic influenza A/H1N1v than observed with seasonal flu. However, consequences in the Northern hemisphere were less dramatic than anticipated. Studies from these countries reported case-fatality rate among hospitalized children ranging from 0.6 to 3% , similar to our findings . As previously hypothesized , these North/South differences in patients' outcome could partly be explained Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain", "Passage: In line with previous studies in Spain, during this fourth wave, death rates of infants and young children were particularly high . Because high rates of excess mortality existed in all age groups, lack of acquired immunity from earlier waves may only explain the excess mortality among infants and young children. Antigenic shift or mutation in the virus also could have contributed to the elevated mortality remaining elevated across all ages, but it remains difficult to ascertain the exact mechanisms that shaped the strong wave. Title: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey\nPassage: least 17700 deaths worldwide and the Centers for Disease Control and Prevention reported 59 millions infected people in the USA ). Title: Age- and Sex-Specific Mortality Associated With the 1918\u20131919 Influenza Pandemic in Kentucky", "Passage: Crude rates of mortality due to respiratory conditions displayed a \"W\" shape in fall 1918, peaking in infants, young adults, and seniors . We subtracted baseline mortality in prepandemic years to obtain influenza-attributable excess mortality in fall 1918 . The highest rates of influenza-related excess mortality were found in infants <1 year old. Three breakpoints were identified in the age-specific mortality curve: a minimum, at age 9.7 years , with a rate of 15 deaths per 10 000; a maximum, at age 25.6 years , with a rate of 80 deaths per 10 000; and a second minimum, at age", "Title: Viral factors in influenza pandemic risk assessment\nPassage: 5. Finally, the infection must spread beyond the local area to infect members of distant populations, a process accelerated by modern global travel . This step and the one before are enhanced if the level of population susceptibility is high, as occurs when the surface proteins of the new strain are dissimilar to those on any currently or recently circulating human influenza A strains. Title: Viral factors in influenza pandemic risk assessment", "Passage: 4. The infection must be transmitted to additional humans, avoiding an \"early\" termination of the transmission chain due to chance. Such early termination is a significant risk given the relatively low infectiousness of influenza and the moderate degree of overdispersion in the number of secondary cases infected by each case, both of which contribute to the probability that a transmission chain will terminate by chance . It must also avoid extinction due to deliberate control efforts put in place by public health authorities . Title: Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China", "Passage: influenza viruses with high infectivity and widespread outbreak patterns, these two AIVs often cause sporadic and small outbreaks, despite the lack of human-to-human transmission ability, so other more complex reasons were involved. Because these two viruses are associated with both wild and domestic bird populations, it is likely that environmental factors play a significant role in the spread of the viruses. Generally, wild birds may act as the primary spreading agent for the outbreak of the influenza virus 10 . After the movement of the virus from wild birds to poultry, the virus may spread from flock to flock and Title: Viral factors in influenza pandemic risk assessment\nPassage: available for study . Multiple virus-host interactions are necessary for replication and onward transmission; the differences in the genetic requirements to accomplish each of these interactions in humans versus other animals provide a barrier to sustained transmission following spillover .", "Title: Strategies for Pharmacological Organoprotection during Extracorporeal Circulation Targeting Ischemia-Reperfusion Injury\nPassage: In 1885 two physicians invented a \"respiration system\" which could be considered as a first prototype of a heart-lung machine: Maximilian von Frey and his colleague Max Gruber both working at the Carl-Ludwig Institute in Leipzig developed a machine capable of perfusing and oxygenating isolated organs . However, this machine was intended to be used for basic research and not for open heart operations. Nearly, 70 years later in 1954 Gibbon designed a device which was able to bypass heart and lung and he also was the first cardiac surgeon who used it during open heart operations . This heart-lung Title: C3P3-G1: first generation of a eukaryotic artificial cytoplasmic expression system", "Passage: excitation filters under oil immersion with image magnification and processed with Leica LAS-AF and ImageJ analysis software. Title: C3P3-G1: first generation of a eukaryotic artificial cytoplasmic expression system\nPassage: were separated over a 20% polyacrylamide/8 M urea gel, prior to phosphorimaging. Title: Delivery Systems for Intradermal Vaccination\nPassage: Vaccines for smallpox have been delivered to the skin dating back to Edward Jenner's first experiments in 1796 demonstrating that exposure to cowpox could protect against smallpox infection. A variety of scarification techniques and devices have been used to allow virus introduction, including knives, needles, scalpels, and rotary lancets. During the global smallpox eradication campaign, both multi-dose nozzle jet injectors and bifurcated needles were used for ID vaccinia virus inoculation .", "Title: Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies\nPassage: The physician questionnaire contained three questions about environmental exposures that had been previously suggested to be possibly associated with the onset of JDM . These included whether the patient had any documented infections, received any immunizations or took any medications within 6 months before illness onset. The questionnaire also included an additional open-ended question about other environmental exposures within 6 months before illness onset relating to other possible triggers of disease and to specify these and when they occurred. Stressful life events were categorized as major vs minor and as One hundred and twenty-one patients were tested by IP immunoblotting. Title: Risk factors for multidrug-resistant pathogens in bronchiectasis exacerbations", "Passage: Data collected were demographic, diagnosis of BE, smoking, alcohol abuse and flu vaccine status. Comorbidities were also recorded and age-adjusted Charlson score. Data related to prior microorganisms isolation, number of exacerbations in the previous year, bronchiectasis severity scores were also recorded. Chronic and concomitant medication included bronchodilators, corticosteroids, theophylline, inhaled/nebulized antibiotics, proton pump inhibitors, long-term oxygen therapy and mucolytic drugs. A history of prior exacerbations and hospitalization during the previous year were also detailed. Title: CDC Summary 21 MAR 2020,\nPassage: If you are a healthcare provider, use your judgment to determine if a patient has signs and symptoms compatible with COVID-19 and whether the patient should be tested. Factors to consider in addition to clinical symptoms may include: Title: Risk factors for infectious complications of ANCA-associated vasculitis: a cohort study", "Passage: A recorded severe infectious complication was defined as implying the administration of an antimicrobial medication for an observable clinical, microbiological and radiologic suspected infection requiring hospitalization. Immediate dialysis was defined as the clinical necessity of renal replacement therapy on admission. The first immunosuppressive agent used in addition to corticosteroids was termed induction therapy. The immunosuppressive regimen used during follow-up was termed the maintenance agent. The diagnosis criteria for deep fungal infection included clinical manifestations, such as fever, cough, diarrhoea or lower urinary tract symptoms, and the detection of fungi in sputum, urine, stool or tissue specimens. Cytomegalovirus infection was diagnosed", "Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen\nPassage: The vacuolar-type H + -ATPase is the major proton pump responsible for acidification of intracellular compartments in eukaryotic cells . The enzyme consists of two multi-subunit complexes, the soluble V 1 transmembrane V o subcomplex required for the proton transport across membranes . In most cell types v-ATPases are only expressed in the endomembrane system to regulate and maintain the acidic pH of intracellular compartments such as lysosomes, endosomes, the Golgi apparatus, secretory granules and coated vesicles . The function of v-ATPases is essential for cellular processes such as vesicular trafficking, receptor-mediated endocytosis and protein degradation and processing. In specialized Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: Text: The vacuolar-type H + -ATPase is the major proton pump responsible for acidification of intracellular compartments in eukaryotic cells . The enzyme consists of two multi-subunit complexes, the soluble V 1 transmembrane V o subcomplex required for the proton transport across membranes . In most cell types v-ATPases are only expressed in the endomembrane system to regulate and maintain the acidic pH of intracellular compartments such as lysosomes, endosomes, the Golgi apparatus, secretory granules and coated vesicles . The function of v-ATPases is essential for cellular processes such as vesicular trafficking, receptor-mediated endocytosis and protein degradation and processing. In Title: The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen", "Passage: specialized cell types including osteoclasts and renal epithelial cells, v-ATPases can also be expressed on the plasma membrane, where they pump protons into the extracellular space . In cancer cells v-ATPases are expressed on the plasma membrane in order to eliminate toxic cytosolic H + . Most importantly, v-ATPases contribute to the acidic tumor microenvironment, which leads to the activation of proteases, thus facilitating tumor cell migration, invasion and angiogenesis . Since the inhibition of v-ATPase was shown to reduce the invasiveness of cancer cells and metastasis formation , this enzyme has emerged as a promising drug target in the Title: A cell-based assay for CD63-containing extracellular vesicles", "Passage: of V 1 -ATPase complex with the V 0 complex is a key regulatory step for many cellular pathways including exocytosis of synaptic vesicles . The V 0 -V 1 ATPase complex has been shown to recruit key signaling machinery such as the mTOR kinase that sense endolysosomal function and generate an appropriate response to regulate protein synthesis and cholesterol transport ). Kozik et al, found an important role for V-ATPase in clathrin-coated vesicle formation . Johnson et al, found that lower V-ATPase activity coincided with localization of endolysosomes to the cell periphery , which could increase the probability of", "Title: Vaccines for the future: learning from human immunology\nPassage: Although the RV144 trial has shown the benefit of a primeboost strategy for a preventive vaccine against HIV, it is still not clear which are the effector mechanisms elicited by the vaccine that protected some of the subjects from HIV infection. For difficult intracellular pathogens such as HIV and HCV, protection probably arises from the integration of different effector mechanisms of the appropriate quality. Therefore, correlates of protection are not easily measured by simple antibody or T cell assays, but require more complex readouts. With the progress of genomics it is possible to generate a lot of high-throughput data from Title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?", "Passage: readily measured also play key roles in protection . It is likely that the mechanism of protection and protective level of a particular immune component may well differ in an experimental model in NHPs, challenged in a manner that may not accurately reflect natural exposure and in humans exposed to natural infection. This highlights the importance of not being over-reliant on immunological correlates derived from pre-clinical testing. Clearly, different vaccine delivery methods induce qualitatively different immune responses; induction of long-lasting humoral immunity in the absence of T cells seems unlikely, so the ability of prime-boost regimens to induce durable CMI Title: A Novel Vaccine against Crimean-Congo Haemorrhagic Fever Protects 100% of Animals against Lethal Challenge in a Mouse Model", "Passage: Most clinical CCHF immunity studies have examined serum antibody levels against the nucleoprotein . Patients with a fatal outcome have a weak or absent antibody response, and Ozturk et al found significant differences between IgM and IgG levels in fatal vs. non-fatal cases . However, other studies were unable to find a significant relationship between the presence of IgM and IgG antibodies and clinical outcome, but found that viral load was a better predictor of prognosis . Virus titres decreased in survivors during the first week of disease, independently of antibodies, suggesting a critical role of innate or cellular immune Title: Clinical vaccine development", "Passage: In the traditional paradigm, disease caused by vaccination has been a serious problem . Rappuoli has stressed the methodological approaches used to overcome the risks of vaccination in the 21st century . In addition, thanks to improvements in genomic techniques, new vaccine-design methods, such as reverse vaccinology , have enabled the high-throughput screening of vaccine candidates with greater confidence in their safety profiles. The characteristics Table 3 . New strategies for improving vaccine safety Screening for sequences homologous to proteins encoded by the human genome to remove sequences mimicking self-antigens Immunohistochemistry to check cross-reactions with human tissues Multiple cytokine induction", "Title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France\nPassage: Text: In order to monitor the spread of influenza and alert health handlers, several epidemiological tools have been developed. In France, a network of 1300 general practitioners, ''R\u00e9seau Sentinelles'', working throughout the country, provides real-time clinical data used to evaluate regional and national influenza spreading . The criteria used by this network to define clinical influenza-like illness are the occurrence of a sudden fever above 39uC with myalgia and respiratory signs. In general no formal viral diagnosis is carried out. The Groupes R\u00e9gionaux d'Observation de la Grippe is a second French network that surveys the emergence and the spread of Title: Epidemiology and Viral Etiology of the Influenza-Like Illness in Corsica during the 2012\u20132013 Winter: An Analysis of Several Sentinel Surveillance Systems", "Passage: The French Institute for Public Health Surveillance developed in 2003 a syndromic surveillance system based on the activity of emergency health professionals through an organization called SOS M\u00e9decins, which is the first emergency network of GPs and health care in France . In Corsica, this emergency general practice surveillance system was implemented in December 2010. It is based on the activity of 11 GPs covering a population of 100 000 habitants and responding to private house calls 24 h a day, 7 days a week . The GPs report on a daily basis the sociodemographic and medical data for each Title: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in R\u00e9union Island, 2011-2012", "Passage: Data and swabs result from a surveillance system that received regulatory approvals, including the CNIL approval in July 2012. All the patients have received oral information and gave their consent for swab and data collection. Data were collected for surveillance purpose and are totally anonymous. Title: Epidemiology and Viral Etiology of the Influenza-Like Illness in Corsica during the 2012\u20132013 Winter: An Analysis of Several Sentinel Surveillance Systems", "Passage: The surveillance of ILIs is conducted in Corsica by five systems, described in detail below , the first of which is the Corsican Sentinelles network. The GPs of the Corsican Sentinelles network participate in the nationwide continuous surveillance of the French Sentinelles network by reporting each week the number of new consultations for several health indicators, including ILIs . This system has been strengthened in Corsica since 2006-2007, and it currently includes 47 GPs throughout the island . Of these, 19 participated in the 2012-2013 virological surveillance of ILIs .", "Title: Novel Identified HLA-A*0201-Restricted Hantaan Virus Glycoprotein Cytotoxic T-Cell Epitopes Could Effectively Induce Protective Responses in HLA-A2.1/K(b) Transgenic Mice May Associate with the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: According to the diagnostic criteria from the Prevention and Treatment Strategy of HFRS described by the Ministry of Health, the People's Republic of China, the severity degree of HFRS disease could be classified into four clinical types: mild, moderate, severe, and critical . Mild: mild renal failure without an obvious oliguric stage; moderate: obvious symptoms of effusion , uremia, hemorrhage into the databases under the analysis options of HLA-A*0201 and nine-mer peptide. Based on the results predicted by BIMAS and SYFPEITHI, nine-mer peptides of HTNV GP were synthesized at 90% purity as assessed by high-performance liquid chromatography and mass spectrometry Title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome", "Passage: higher than those mild patients . These data suggest that harboring rs12252 C allele increases the risk of suffering severe disease in HTNV-infected individuals, with an odds ratio of 2.124 . For genotypes, 43.90% of the severe patients carried the CC genotype, a significantly higher frequency than the control Han Chinese per 1,000 genomes sequence database as well as mildly infected patients . However, mildly ill individuals did not exhibit a Fisher's exact test was used to test the association between rs12252 allele/genotype and HFRS severity. The plasma HTNV load in CC genotype patients and CT/TT genotype patients, tested by Title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing", "Passage: In 2009, a previous study showed a phylogeographic link between four US Soldiers diagnosed with HFRS due to exposure at military training sites and A. agrarius positive for HTNV based on a partial sequence of HTNV M segment 20 . This analysis provided mechanisms to identify the location where the soldiers most likely acquired HTNV infections and under what conditions. The analysis of 354 bp-partial sequence of HTNV M segment between HFRS patients and rodent hosts may be insufficient to better define the phylogeographic link for future cases because of the low resolution. A recent study demonstrated that whole genome Title: A vascular endothelial growth factor receptor gene variant is associated with susceptibility to acute respiratory distress syndrome", "Passage: Hardy-Weinberg equilibrium were assessed with R 3.2.2 . SNP minor allele frequency in the control group was calculated and compared to the values reported for the Iberian Population in Spain from The 1000 Genomes Project to assess its consistency .", "Title: Chikungunya: A Potentially Emerging Epidemic?\nPassage: CHIKV has been isolated into three genotypes based on phylogenetic studies. These genotypes, based on the gene sequences of an Envelope protein , are Asian, East/Central/ South African, and West African . Using phylogenetic models, Cherian et al. estimate that the Asian genotype of CHIKV emerged between 50 and 310 y ago, and the West and East African genotypes diverged between 100 and 840 y ago . Since then, CHIKV has come a long way, with several mutations incorporated, and has continued to wreak epidemics in several regions. Recent activities of CHIKV include the Indian epidemic in 2005-2006, which was Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: followed by a sudden explosion of cases in 2007. An estimated 1.3 million people across 13 states were reported to be infected in India , and CHIKV was also widespread in Malaysia, Sri Lanka, and Indonesia . In July-August of 2007, CHIKV was reported in Italy, probably brought in by travelers from CHIKV-prone regions of India, Africa, and Indian Ocean islands such as Mauritius, Madagascar, and Seychelles. Few of the Italian isolates were found to have evolved from the Kerala isolate, which was associated with a A226V shift in E1 gene that represents a successful evolutionary adaptation in the mosquito Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: In recent times, with an increase in global travel, the risk for spreading CHIKV to non-endemic regions has heightened . Several travelers have brought CHIKV home with them after visiting areas with actively infected populations . Such cases have been documented in European countries, Australia, Asia, and the United States . The United States has already reported at least twelve cases of travel-associated CHIKV, while France has reported 850 cases, and the United Kingdom 93 . Beyond this, CHIKV-infected travelers have also been diagnosed in Australia, Belgium, Canada, Czech Republic, French Guiana, Germany, Hong Kong, Italy, Japan, Kenya, Malaysia, Martinique, Title: Chikungunya: A Potentially Emerging Epidemic?", "Passage: CHIKV mosquito-borne disease has caused massive outbreaks for at least half a century but is no longer confined to the www.plosntds.org developing nations. It began to encroach into the boundaries of the developing world. As a result, the NIAID has designated CHIKV as a Category C pathogen alongside the influenza and SARS-CoV viruses . Realization of the potential severity of this disease is exigent; for instance, if used as a biological weapon, the world economy could be severely crippled; if enough members of the armed forces were to become infected during a military deployment, military operations could be significantly affected.", "Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: Only the study by Vijh et al. indicated that exposure to the empty vector may completely abrogate immune responses against the delivered antigens . However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: For viral vectors, the impact of cell-mediated immunity was more pronounced, and as depicted in Table 2 , almost always resulted in a reduction in the subsequent immune response. Presumably this is because viruses will induce neutralizing antibody on the first dose, and in subsequent doses this antibody will limit the number of transduced cells, therefore limiting the responses. This is particularly a problem with a common viral vector such as Ad, where a large proportion of the population will have immunological memory against common serotypes . As these authors conclude, it will be possible to utilize such vectors only Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: All these studies on the effect of pre-existing immunity discuss the impact on humoral responses. Sevil Domenech and colleagues reported that pre-exposing animals to the homologous Salmonella vector leads to a significant reduction in CD8 + responses; however, exposure of animals to a heterologous strain leads to significantly higher CD8 + responses . Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?\nPassage: expressing tetC, induced much lower anti-tetC responses than mice that had not been primed. This argues strongly that prior immunological immunity to the vector can seriously dampen subsequent antigen-specific humoral responses. Whether the same is true for cellular responses was not evaluated.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: The key limitations of genetic material detection are the lack of knowledge of the presence of viable virus, the potential cross-reactivity with non-specific genetic regions and the short timeframe for accurate detection during the acute infection phase. The key limitations of serological testing is the need to collect paired serum samples from cases under investigation for confirmation to eliminate potential cross-reactivity from non-specific antibodies from past exposure and/or infection by other coronaviruses. The limitation of virus culture and isolation is the long duration and the highly specialized skills required of the technicians to process the samples. All patients recovered. Title: Virus contaminations of cell cultures \u2013 A biotechnological view", "Passage: Only few harvests need to be tested . c Old cells may be from production runs or from a separate culture kept in continuous culture for a long period and prepared for this analysis of 'limit of cell age' only . Extensive testing performed as part of the qualification of the MCB regarding absence of latent virus, inducible by cultivation on production conditions. d A very large sample volume for testing would be required for statistics of a sufficiently sensitive detection of low virus titers. Title: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus\nPassage: A limitation of PCR methods is that false-negative results may occur due to sequence variation in primer and probe targets and is particularly relevant for the detection of emerging viruses. However the use of multiple targets can reduce such limitations, and may serve as a means of confi rming positive results. Mahony Title: How necessary is a fast testkit for mitigation of pandemic flu?", "Passage: implemented with the abovementioned conditions. The critical issue that follows is then how limited resources such as antiviral drugs and testkits can be used effectively with those conditions.", "Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: other personal protection as established by the EMICT. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: China Hospital of Sichuan University. The EMICT training for staff is mainly involves Title: Iranian Emergency Medical Service Response in Disaster; Report of three Earthquakes", "Passage: in provincial hospitals and hospitals of other provinces and in addition facilitated the registration of patients' information and follow up. The uniform Incident Command System was developed through the EMS of the country for the integrated coordination and management of health services so that the management of facilities and resources of cooperator organizations, support, and even military forces was carried out by this system. This resulted in the transfer of a significant number of injured persons within a limited time frame, which certainly affected the mortality and morbidity of traumatized patients that were timesensitive. Title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management\nPassage: EMICT: emergency management and infection control team", "Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective\nPassage: The selected ribozymes were able to replicate, cleave, join, and form peptide bonds. They can polymerize progeny chemically, allow for mutations to occur and can evolve. One molecule serves as catalyst, the other one as substrate. Replication of ribozymes was demonstrated in the test tube . Ribozymes can form peptide bonds between amino acids . Thus, small peptides were available by ribozyme activity. Consequently, an RNA modification has been proposed as peptide nucleic acid , with more stable peptide bonds instead of phosphodiester bonds . Replication of RNA molecules can be performed chemically from RNA without polymerase enzymes. In addition, Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: tRNA-amino acid complexes can find RNAs as \"mRNAs.\" Such interactions could have contributed to the evolution of the genetic code. This sequence of events can lead to primitive ribosome precursors. Ribozymes are the essential catalytic elements in ribosomes: \"The ribosome is a ribozyme\" , supplemented with about a hundred scaffold proteins later during evolution. The proteins have structural functions and contribute indirectly to enzymatic activity. Are these ribosomebound ribozymes fossils from the early Earth? Small peptides can be formed by ribozymes before ribosomes evolved, whereby single or dimeric amino acids may originate from the universe . Title: Viruses and Evolution \u2013 Viruses First? A Personal Perspective", "Passage: Small peptides with basic amino acids can increase the catalytic activity of ribozymes as shown in vitro . Such proteins are known as RNA-binding proteins from RNA viruses that protect the RNA genome, with motifs such as RAPRKKG of the nucleocapsid NCp7 of HIV . Peptides can enhance the catalytic activity of ribozymes up to a 100-fold . Such peptides of RNA viruses serve as chaperones that remove higher ordered RNA structures, allowing for more efficient interaction of RNA molecules and increasing transcription rates of RNA polymerases . Ribonucleoproteins may have also been functionally important during the evolution of ribosomes Title: Can\u2019t RIDD off viruses", "Passage: produce dsRNA by annealing of RNA derived from transcription of both strands in the same viral genomic loci, which are probably detected by the cytoplasmic pool of OAS proteins . Post-activation the OAS enzymes synthesize 2-5A molecules in a non-processive reaction producing oligomers which, although potentially ranging in size from dimeric to multimeric, are functionally active only in a trimeric or tetrameric form . These small ligands, which bear phosphate groups at the 5 end and hydroxyl groups at the 2 and 3 positions, serve as co-factor which can specifically interact with and thereby allosterically activate, existing RNaseL molecules .", "Title: Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses\nPassage: The A549 cell is a transformed adenocarcinoma cell line derived from an explanted tumor from a 58-year-old Caucasian male. While this study provides some important information about how multiple IAV strains induce changes in the cellular proteome of these cells, it will be important to perform similar assays in more physiologically-relevant primary cells to allow the comparison and possible identification of common cellular processes that might be amenable to therapeutic intervention. Title: Alternative Experimental Models for Studying Influenza Proteins, Host\u2013Virus Interactions and Anti-Influenza Drugs", "Passage: The A549 human lung adenocarcinoma epithelial cell line and the Calu-3, a human bronchial epithelial cell line, have been widely used to study influenza virus-host interactions , viral protein biochemistry , drug studies and for performing large-scale screens, such as a CRISPR activation screen, to identify genes that inhibit influenza virus infection when they are overexpressed . Title: Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice", "Passage: LA4 cells were acquired from Prof. Robert Snelgrove and were originally obtained from American Type Culture Collection . LA4 cells were maintained in Ham's F12 medium conditioned with 2mM L-glutamine and 15% FBS. Human embryonic kidney , human lung adenocarcinoma epithelial cells and Madin-Darby canine kidney cells cells were maintained in Dulbecco's modified Eagle's medium supplemented with 10% FBS and 1% penicillin/streptomycin . A549-Luc cells were constructed and maintained as previously described . L929 cells were a gift from Caetano Reis e Sousa, The Francis Crick Institute, UK, and were cultured with 10% FBS, 0.05mM \u03b2-mercaptoethonal and 1% penicillin/streptomycin in Title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs", "Passage: The Vero E6 cell line, derived by immortalization of African Green monkey kidney cells, is the most commonly used cell line for testing antivirals against filoviruses. EBOV propagates very well in this cell line, and many laboratories, including ours, generate their virus stocks and determine virus titers in Vero E6 cells. However, the argument to use a cell line with more relevance to human disease has come up repeatedly. Hence, the human liver cancer cell line, Huh 7 and human MDMs were chosen for these studies. Macrophages are relevant to human disease, and they are considered to play an important", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: The majority of specimen testing to date has employed validated RT-rtPCR assays shown to be sensitive and specific . The RealStar\u00ae kit uses these WHOrecommended assays . The target sequences of these screening assays have not changed among genomes examined until at least mid-2015 . Other RT-rtPCR assays have been developed and validated for use as laboratory-based diagnostic tools . Additionally, loop-mediated or recombinase polymerase isothermal assays have been designed for field deployment. Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: described, cell culture is a slow, specialised and insensitive method while PCR-based techniques are the preferred method for MERS-CoV detection. Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms. LRT samples are also best for attempting isolation of infectious virus, although the success of culture is reduced when disease persists . Recommended sample types include bronchoalveolar lavage , tracheal/tracheobronchial aspirate, pleural fluid and sputum . Fresh samples yield better diagnostic results than refrigerated material and if delays in testing of \u226572 h are likely, samples should be frozen at \u221270\u00b0C . If available, lung biopsy or autopsy tissues can also be tested . Title: MERS coronavirus: diagnostics, epidemiology and transmission", "Passage: The detection of MERS-CoV antigen has not been common to date but the combination of short turnaround time from test to result, high throughput and identification of viral proteins makes this an attractive option. Detection of viral proteins rather than viral RNA indicates the likely presence of infectious virus. The first rapid immunochromatographic tool described could detect recombinant MERS-CoV nucleocapsid protein from DC nasal swabs with 94 % sensitivity and 100 % specificity compared to RT-rtPCR . A different approach used a monoclonal antibody-based capture ELISA targeting the MERS-CoV nucleocapsid protein with a sensitivity of 10 3 TCID 50 and", "Title: Smallpox and Season: Reanalysis of Historical Data\nPassage: Smallpox is the only disease to have been eradicated worldwide . Despite the success story of vaccination and other public health interventions, the number of susceptible individuals has grown to date following cessation of routine vaccination, and the threat of bioterrorist attack has led to debates on countermeasures in such an event . Various mathematical studies have been conducted as part of a preparedness program, including large-scale simulation of a bioterrorist attack and the public health countermeasures against it . Theoretical studies on the spread of smallpox include not only simulations but also quantitative analysis of historical data . A Title: Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model", "Passage: Vaccination of individuals prior to the discontinuation of routine vaccination may provide some, possibly considerable, protection against infection , although it may also result in more mild cases which may be harder to detect. Title: Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model", "Passage: Concerns about intentional releases of smallpox have prompted extensive preparations to improve our ability to detect and respond to an outbreak of smallpox . Many factors contribute to the public health challenge of understanding and preparing for smallpox, including the age and quality of epidemiological data on native smallpox and the smallpox vaccine, the difficulty of extrapolating that data to our current populations, the possible terrorist use of altered smallpox, our ignorance of terrorist methods of release, and the relatively high risk of adverse events caused by the smallpox vaccine. Title: Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model", "Passage: Vaccination with vaccinia virus provided substantial protection against infection. Dixon assessed the risk of infection for an individual successfully vaccinated 3 years prior to exposure to be 0.1% the infection risk of an unvaccinated individual . However, smallpox vaccination did not always take when applied, and moreover, in many instances, individuals who experienced a repeated vaccination failure developed severe smallpox upon exposure. The probability of a successful take depended on the vaccination method used; we assume that the take rate is between 95% and 100% . In addition to protection against infection, vaccination could in many cases modify the course", "Title: Severe imported malaria in an intensive care unit: a review of 59 cases\nPassage: all the samples tested. Title: Severe imported malaria in an intensive care unit: a review of 59 cases\nPassage: Forty one were Portuguese emigrants working in Africa ; seven patients were tourists and other seven lived in Africa and came to Portugal , and four worked in boats that had made several stops in seaports along the way. All but three had returned from sub-Saharan Africa: 48 from former Portuguese colonies in Africa -Angola , Mozambique , Guinea-Bissau and Sao Tome and Principe ; the others had returned from Senegal and Gabon, Malawi, Burkina Faso, Central African Republic, Nigeria, and C\u00f4te d'Ivoire, one patient from each country; two other patients had returned from Thailand and one from the Philippines. Title: CDC Summary 21 MAR 2020,\nPassage: Imported cases in travelers Title: Severe imported malaria in an intensive care unit: a review of 59 cases", "Passage: The present study includes expatriates , people that were born and live in Africa travelling to Portugal to visit friends and relatives, immigrants and those travelling for business or tourism.", "Title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond\nPassage: Noroviruses are part of the family Caliciviridae and outbreaks of norovirus gastroenteritis have been reported in cruise ships, health care settings, schools, and in the military, but norovirus is also responsible for around 60% of all sporadic diarrhea cases , reviewed in the literature . The pathogenesis of norovirus infection has been tested in vivo. Filtrated norovirus was given to healthy volunteers after which most of them developed diarrhea . Culturing of the virus, however, has been a problem since its discovery, yet one study has recently described the cultivation of norovirus in B cells, and has revealed that co-factors, Title: Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future", "Passage: Noroviruses, a member of the family Caliciviridae, are one of the leading causes of viral gastroenteritis in humans, accounting for approximately 18% of all cases of diarrhea worldwide . In developed countries, noroviruses have been recognized as the most common cause of non-bacterial diarrheal outbreaks in both children and adults, responsible for around 19-21 million illnesses, 56,000-71,000 hospitalizations and 570-800 deaths annually in the US alone . Although rotaviruses are regarded as the major cause of childhood diarrhea in developing countries, noroviruses are now fast emerging as the most prevalent etiological agent of severe gastroenteritis in children in countries that Title: Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan", "Passage: specific immunity. 6 Published studies have reported that around 30% of norovirus infection remains asymptomatic, 7 while such asymptomatically infected individuals are known to excrete substantial volume of viruses. 8, 9 Vomit from infectious individuals contains over 10 7 copies=gram of noroviruses, 8, 9 and infectious vomitus is known to be sometimes aerosolized, 10, 11 making it difficult to prevent secondary transmissions. The virus spreads through fecal-oral routes, such as via contaminated water, food, and people's contaminated hands. 12, 13 Published studies indicate that infections associated with environmental contaminants are mainly caused by contaminated water or foods , 11 accounting Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Noroviruses cause approximately 90% of all outbreaks of epidemic gastroenteritis and are an important source of foodborne outbreaks globally . Though transmission occurs primarily via the fecal-oral route, there is also reported evidence of transmission through vomitus . Clinical symptoms include abdominal cramps, nausea, a high prevalence of vomiting, and diarrhea . Most published estimates for noroviruses were consistent with an incubation period of 1 to 2 days .", "Title: Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for \u201cHoles\u201d in the T Cell Repertoire\nPassage: 0#S#1 for all peptides y. The peptide-similarity score is asymmetric i.e. S?S despite W being symmetric. The reason is that the extreme values cannot be guarantied to be identical for any pair of peptides . Reference peptides x which are dominated by amino acids like tryptophan that hardly ever substitute, will have few highly similar peptides which satisfy the condition: S < 1. In contrast, reference peptides which are enriched in amino acids that are more likely to substitute have a greater number of highly similar peptides. This property is captured by the asymmetry of S. Title: Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for \u201cHoles\u201d in the T Cell Repertoire", "Passage: to our knowledge for the first time, that the basis of T cell recognition is amino acid similarity, defined in terms of biochemical properties of amino acid side chains. Title: Overlapping genes and the proteins they encode differ significantly in their sequence composition from non-overlapping genes\nPassage: the amino acids tyrosine and isoleucine, the synonymous codon TAT, and in amino acids with a low codon degeneracy . We confirmed the relevance of the 20 critical composition differences with the Wilcoxon test for paired data. In all cases, we found a z score largely exceeding the cut-off of significance . Title: Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for \u201cHoles\u201d in the T Cell Repertoire", "Passage: of non-identical amino acid between cross-reactive constituents. We find that the majority of the seemingly ''unrelated'' cross-reactive peptides have a significantly higher biochemical similarity to each other than what would be expected from truly ''unrelated'' peptides. This is especially true for peptides with very limited identity. To our knowledge this is the first study that analyzes a large set of cross-reactive peptide-MHC combinations and demonstrates that the cross-reactivity can, up to a certain extent, be predicted.", "Title: In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions\nPassage: Flaviviruses are small, highly organized enveloped viruses with a spherical shape . They contain a positive-sense RNA genome packaged by the viral capsid protein. The nucleocapsid is surrounded by a lipid bilayer containing the viral membrane protein E. Flaviviruses infect cells by receptor engagement at the plasma membrane, endocytic uptake, and a membrane fusion reaction triggered by the low pH of the endosome compartment . The viral E protein binds the receptor and drives the fusion of the viral and endosome membranes to initiate virus infection. The pre-fusion structure of the E protein ectodomain shows that E contains three domains Title: The role of viral persistence in flavivirus biology", "Passage: DIII is associated with receptor binding and is also a target for several neutralizing monoclonal antibodies. Crystal structures of the E protein from several flaviviruses all show similar secondary structure and domain organization . The E protein is important in determining neuroinvasiveness and neurovirulence for several MBFVs . For WNV, JEV, and DENV, mutations in the E protein affect fusion and receptor binding with target cells The E protein was first described in 1995 and later has been extensively defined and crystalized for many other flaviviruses . TBFV E protein is important for determining neurovirulence and neuroinvasiveness Nonstructural Proteins NS1 Title: A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes", "Passage: assays. We next investigated the details of flavivirus-AaHig interaction. The length of the Dengue E protein is approximately 500 amino acids, of which the N-terminal 400 amino acids form an ectodomain. The ectodomain consists of three domains that are referred to as envelope protein domain I , ED2, and ED3 . Both ED1 and ED2 are structural domains, and the linear motifs of ED1 and ED2 are interlaced. However, the ED3 domain consists of an entirely linear sequence . Based on these defined domains, we first cloned and expressed two truncated peptides in Drosophila S2 cells: the ED1+ED2 and ED3 Title: Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides", "Passage: Only a few examples of viral entry inhibitors with activity against the primarily beta sheet envelope proteins from flaviviruses have been described . However, few of these have taken advantage of the available crystal structures of flavivirus E proteins, including both pre-fusion and post-fusion forms . The authors of some of these structures have predicted that several regions of these proteins might be targets for inhibition . Here we report the use of structural data from the pre-fusion dengue virus-2 E protein as a model for a computational approach to the design of new peptide inhibitors of DENV-2 entry. This", "Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: For the 143 HMPV genomes, we checked sequence conservation at transcriptional control regions, at the termini of each gene, as well as the lengths of intergenic sequences between gene boundaries. The length of the F-M2 intergenic region was different between group A and B viruses, that is, 13 nt and 2 nt, respectively. The SH-G and G-L intergenic regions were the longest, up to 125 nt and to 190 nt, respectively. Consensus nucleotides at the putative start and end regions flanking the ORF of the viral genes are shown in Fig. 1 . The gene-start and -end regions of N Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: For the 143 HMPV genomes, we checked sequence conservation at transcriptional control regions, at the termini of each gene, as well as the lengths of intergenic sequences between gene boundaries. The length of the F-M2 intergenic region was different between group A and B viruses, that is, 13 nt and 2 nt, respectively. The SH-G and G-L intergenic regions were the longest, up to 125 nt and to 190 nt, respectively. Consensus nucleotides at the putative start and end regions flanking the ORF of the viral genes are shown in Fig. 1 . The gene-start and -end regions of N Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia", "Passage: Whole genome sequencing was successful for all 5 clinical samples that were attempted. A single genomic sequence was obtained from each sample, and the length of the 5 new HMPV genomes ranged from 13,097 to 13, 134 nt . Sequencing and data assembly parameters, including coverage depth are shown in Table 1 . Title: Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia\nPassage: Whole genome sequencing was successful for all 5 clinical samples that were attempted. A single genomic sequence was obtained from each sample, and the length of the 5 new HMPV genomes ranged from 13,097 to 13, 134 nt . Sequencing and data assembly parameters, including coverage depth are shown in Table 1 .", "Title: Virus contaminations of cell cultures \u2013 A biotechnological view\nPassage: serum-free or protein-free media . With respect to the production of viral vaccines, the first serum-free viral vaccines were developed and tested in clinical studies , and are going to be put on the market. Title: Human mobility and the worldwide impact of intentional localized highly pathogenic virus release\nPassage: can be shared with government officials and biosecurity researchers upon request. Title: Virus contaminations of cell cultures \u2013 A biotechnological view", "Passage: A further relevant example from the production of poliovirus vaccine is provided by SV40, a polyomavirus which is an extremely common infection of macaques and rhesus monkeys where it persists in the kidneys in a latent form without causing a cytopathic effect . This virus grows much more slowly than poliovirus and thus an infection might not be observed during the vaccine production. It is estimated that almost everybody who was vaccinated against poliovirus between 1954 and 1961 also recieved viable SV40 together with the poliovirus vaccine. This is true for the live attenuated as well as for the inactivated Title: Virus contaminations of cell cultures \u2013 A biotechnological view", "Passage: controlled conditions led to the production of better quality animals especially in respect of virus infections . Van Wezel et al. could show, by performing serological tests on 18 captive-bred cynomolgous monkeys and 40 imported wild caught parent animals that most of the wild caught animals were positive for antibodies against herpes simplex B, parainfluenza 3, or measles virus, whereas two thirds of the captive bred animals were only positive for antibodies against rotaviruses. Twenty out of 36 imported animals were positive for foamy virus 1 antibodies whereas these antibodies were not observed in the animals bred in captivity .", "Title: Viral vector-based influenza vaccines\nPassage: viral vectors can easily be propagated to high virus titers and it is relatively easy to insert genes encoding antigens of choice into the vector. Viral vector technology also allows the production of modified influenza viral antigens in vivo. These modifications can improve the immunogenicity of the influenza viral proteins or alter the specificity of the immune response. In this review, we discuss reports on vectored influenza vaccines and discuss their advantages and disadvantages. Title: Virus-Vectored Influenza Virus Vaccines", "Passage: influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. Title: Viral vector-based influenza vaccines", "Passage: vivo. Since the proteins are expressed in their native confirmation, antibody responses of the desired specificities are induced. In addition, viral vectors allow de novo protein synthesis in the cytoplasm of infected cells facilitating endogenous antigen processing and MHC class I presentation of immunogenic peptides, which is a requirement for the efficient induction of virus-specific CD8 C T-cell responses. Although all vectors discussed have their own respective advantages and disadvantages, most are replication-deficient in mammalian host cells and are therefore safe for human use, even in immunocompromised individuals. Pre-existing immunity to the vector may pose a problem for some vectors, Title: Virus-Vectored Influenza Virus Vaccines", "Passage: Influenza vaccines utilizing vesicular stomatitis virus , a rhabdovirus, as a vaccine vector have a number of advantages shared with other RNA virus vaccine vectors. Both live and replication-defective VSV vaccine vectors have been shown to be immunogenic , and like Paramyxoviridae, the Rhabdoviridae genome has a 3'-to-5' gradient of gene expression enabling attention by selective vaccine gene insertion or genome rearrangement . VSV has a number of other advantages including broad tissue tropism, and the potential for intramuscular or intranasal immunization. The latter delivery method enables induction of mucosal immunity and elimination of needles required for vaccination. Also, there", "Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection\nPassage: even a fraction of the morbidity and mortality of the pandemic H1N1 and H5N1 viruses would have dire consequences. Antibodies play a key role in protection against influenza infection in vivo . The fact that there were little or no preexisting antibody titers present before the emergence of this pandemic virus, and that the virus atypically caused such severe disease in young adult, illustrates the importance of comprehensively understanding the B cell responses and antibody specificities induced by infection with this influenza virus. Title: Dengue virus compartmentalization during antibody-enhanced infection\nPassage: during antibody-dependent infection. Title: Neutralization Interfering Antibodies: A \u201cNovel\u201d Example of Humoral Immune Dysfunction Facilitating Viral Escape?", "Passage: During the first few days of an infection, the nAb titer is often low, while the titer of non-nAbs is higher and may play a role in the outcome of an infection, as recently observed for influenza A/2009 H1N1 pandemic virus infected patients by To et al. . In particular, this group found that the amount, as well as the avidity, of non-nAbs were higher for patients with severe disease than for those with mild disease. The authors concluded that an exaggerated non-nAb response during the early stage of infection was associated with severe disease . Moreover, the authors speculated Title: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection", "Passage: mice is shown in the lower right of each plot. Infected, untreated mice showed clear signs of sickness around day 4-5 after infection and perished by day 8-9. Prophylactic treatment is shown on the left for comparison. Antibody treatment conferred significant protection as determined by comparison of weights in untreated versus prophylaxis and at the time of treatment versus 12 d after infection . The log-rank test indicated significant survival as well . Figure shows one representative experiments of at least three independent repeat experiments.", "Title: Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review\nPassage: Upward bias could occur because of successive generations of influenza overlapping in small time periods. 15 Indeed, some observed serial intervals in close-contact studies may be between primary and tertiary cases rather than secondary cases. Two studies used modeling to explicitly account for such phenomenon: in both approaches, the modeled mean SI was shorter than the empirical mean of observed values . This suggests that tertiary transmission is always an issue for estimating the serial interval of influenza, and further implies that estimates reported in the other 11 studies could have been biased upwards. Title: Transmission Potential of Chikungunya Virus and Control Measures: The Case of Italy", "Passage: The epidemic transmission process in humans can be modeled by the following system of ordinary differential equations, which has been added to system as modified above : Title: Transmission Potential of Chikungunya Virus and Control Measures: The Case of Italy\nPassage: mobility of humans and vectors. Climate changes could have been playing a role, as the geographical limits of mosquito-borne diseases can be influenced by climate , but this is still debated . Title: Transmission Potential of Rift Valley Fever Virus over the Course of the 2010 Epidemic in South Africa\nPassage: determined plausible reasons for fade-out of the epidemic wave.", "Title: Introducing the Outbreak Threshold in Epidemiology\nPassage: as the fact that the incubation period is around 5 days, by which point it had easily caused more secondary cases. However, in subsequent outbreaks super-spreaders might not be infected early on, allowing more time to contain the spread. Title: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus\nPassage: hospitalization, and ultimately die. 22 Early predictions for incubation time are between 2 and 14 days, based on data from similar coronaviruses. The 14-day criterion for epidemiological risk assumes the longest estimated incubation time. 23 In addition, the World Health Organization has created its own interim case definition. 24 Title: Incubation periods of viral gastroenteritis: a systematic review\nPassage: 5% of cases will exhibit symptoms by 0.9 days after infection and 95% of cases will become symptomatic by 3.3 days . Title: Incubation periods of viral gastroenteritis: a systematic review", "Passage: Based on 106 observations from four observational studies , we estimate the median incubation period for sapoviruses to be 1.7 days with a dispersion of 1.48 .", "Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: new research by other researchers in Kenya and other countries on other health problems. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors\nPassage: A lay summary of the results will be shared with the participating schools and households, as well as and communities surrounding the schools. Manuscripts will be submitted to appropriate journals discussing the methods, statistical analysis and output, and applications of the data in mathematical modelling of respiratory disease transmission and control. Title: Study design and protocol for investigating social network patterns in rural and urban schools and households in a coastal setting in Kenya using wearable proximity sensors", "Passage: it might be worth considering how the proposed proximity data might relate to existing diary-based studies. Title: A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan\nPassage: sample material.", "Title: Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour\nPassage: of the infected person while covering their mouth and nose while coughing or sneezing. The virus will then be transferred to a surface if it is touched by a contaminated hand. A clean hand can also be contaminated if it touches a contaminated surface. Some large droplets with virus on hands can be transferred to the mucous membranes if the student touches his or her own lips, nose or eyes. Some large droplets are resuspended from surfaces to the air because of human activities such as walking. In addition, viruses on hands and surfaces also lose viability over time. Moreover, Title: Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour", "Passage: Virus is transmitted through the air by aerosols within the inspirable size range or smaller; aerosol particles are small enough to be inhaled into the nasopharynx and distally into the trachea and lung. Title: Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour\nPassage: Virus is transmitted through the air by aerosols within the inspirable size range or smaller; aerosol particles are small enough to be inhaled into the nasopharynx and distally into the trachea and lung. Title: Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets", "Passage: M illions of people have lost their lives due to influenza A virus epidemics and pandemics. Prevention and control of IAV infections are based on vaccination and treatment. However, a better fundamental understanding of IAV transmission could help to design additional appropriate intervention strategies, especially in health care settings. Transmission of IAVs between humans can occur via direct or indirect personto-person contact and through the air via respiratory droplets or aerosols. The relative contribution of each route of transmission is still under debate 1-3 , yet it is widely accepted that aerosol or respiratory droplet transmission is the key factor", "Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium\nPassage: are due to the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease . These acute exacerbations are the main cause of morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide. However, due to the complex interactions between the host and the exacerbation agents, the mechanisms of exacerbation may vary considerably in different individuals under various triggers. Acute exacerbations are usually due to the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway . These agents elicit Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: infection may also alter the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth . Furthermore, the destabilization is further compounded by impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms . All these may gradually lead to more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles . These changes may in turn result in more severe and frequent acute exacerbations due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases . Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: Frontiers in Cell and Developmental Biology | www.frontiersin.org mechanisms have been implicated in acute exacerbations during and after viral infection . Murray et al. has underlined the synergistic effect of viral infection with other sensitizing agents in causing more severe acute exacerbations in the airway. This is especially true when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance in particular the late onset of a bacterial infection . On the other hand, viral infections or their components persist in patients with chronic airway inflammatory disease . Hence, their presence may further", "Title: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management", "Passage: With the world having experienced some notable influenza pandemics in the past, a Global Initiative on Sharing All Influenza Data platform was established and was instrumental in the rapid sharing of information by the Chinese scientists regarding the emergence of the COVID-19 virus. Through this platform, scientists from other regions were observed to gain access to information and are, subsequently, able to act in a much faster capacity; like in the case of scientists from the Virus Identification Laboratory based at Doherty Institute, Australia, who managed to grow a similar virus in the laboratory after accessing the data shared by Title: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management", "Passage: With the Coronavirus , it took only 17 days to be identified. The sharing of data has also been quicker, as immediately after the virus' genetic sequence was discovered, Chinese scientists were able to share the information with the WHO, thus helping in its identification and enabling the auctioning of precautionary measures in other countries. Latest technological tools have also allowed for the receipt of information in realtime, in contrast to traditional epidemiological approaches that would have required months to identify the outbreak type . Similarly, though substantial data and information on the disease has been shared, Wetsman acknowledges that Title: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management", "Passage: The timely response by stakeholders in regard to this new outbreak are commendable compared to previous cases. The latter includes the Severe Acute Respiratory Syndrome outbreak in 2002 that took substantial time to identify and be dealt with ; the Ebola outbreak in West Africa in 2013 that took months to determine; and the Zika Virus that was first reported in 2014 before being successfully identified in 2015. Title: Chinese Public Attention to the Outbreak of Ebola in West Africa: Evidence from the Online Big Data Platform\nPassage: public communication and health education, which was helpful to avoid the occurrence of public panics and dispel rumors.", "Title: The Trojan Chicken Study, Minnesota\nPassage: The mean age of those who completed the enrollment questionnaire was 33 years. Eighteen participants were poultry exhibitors, who showed 1-10 birds each . Fifty-five participants of 82 were residents of farms. Title: Participant retention practices in longitudinal clinical research studies with high retention rates", "Passage: Of the 19 participating studies, 13 were prospective cohort studies, 5 were RCTs, and 1 was a quasiexperimental study . Included studies had diverse patient populations, including victims of intimate partner violence, persons living with human immunodeficiency virus and acquired immunodeficiency syndrome , survivors of critical illness and other serious illnesses. The target sample size for studies ranged from 255-10,000. Actual sample recruitment at the time of interview ranged from 205 for the Community Aging in Place -Advancing Better Living for Elders study with older adults aging in place to 2528 for the Alzheimer's Disease Anti-Inflammatory Prevention Trial . Though Title: Suffering a Loss Is Good Fortune: Myth or Reality?", "Passage: The participants were 559 adults who came from 20 Chinese provinces and were engaged in over 50 different occupations. The average age of the participants was 32.1 years . Paper-andpencil questionnaires were completed by 367 participants in the waiting lounge of the Ji'nan West Railway Station, and the other 192 participants completed an e-questionnaire distributed through email. Each participant completed the scales independently and was given a small gift for their participation. Title: Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya", "Passage: However, 135 participants did not participate in the mapping exercise. Reasons for refusal were not recorded, but there were no differences in sex or age distributions in the populations who did and did not participate in the exercise. Of those willing to locate their residence, 61\u00b75% were female compared to 58\u00b79% in the unwilling group . Similarly, the mean age in the adult populations in those unwilling to locate their residence was slightly higher at 37\u00b79 years compared to 35\u00b73 years in those that did attempt the exercise, although the difference was not significant .", "Title: The Trojan Chicken Study, Minnesota\nPassage: This study was reviewed and approved by the University of Iowa's Institutional Review Board and Animal Use and Care Committee. The investigators participated in online human and animal subjects training. Informed consent was sought from participants before they were enrolled. Title: Tracking social contact networks with online respondent-driven detection: who recruits whom?\nPassage: We obtained ethical approval from the Medical Ethical Committee of the University Medical Center Utrecht, The Netherlands . Informed consent was obtained before survey participation. Title: Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk", "Passage: Interviews were conducted over a four month period from May to August 2006, either in person or by telephone. The interviews were conducted by two of the research team members . To maximise consistency of questioning, a semi-structured interview guide was followed in each of the interviews. The questions were open-ended and interviews lasted between 45 minutes to 1 hour. All interviews were audio-taped and then fully transcribed. The transcriptions were checked for accuracy against the taperecordings and then imported into NVivo 7, a qualitative data management software program commonly used in qualitative research . Title: Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1)", "Passage: responses. In contrast, the telephone-based study of Rubin et al. employed a random-digit-dial sampling design, allowing a more representative sample of the general UK population, but their sample was only 997 respondents and the survey was undertaken after media attention had abated, beginning 8 May 2009. Nonetheless, the results reported in this paper are largely congruent with our own results and we see the studies as strongly complementary.", "Title: Generation and comparative genomics of synthetic dengue viruses\nPassage: wildtype DENV-2 virus in comparison to its synthetic constructs. In general, the wildtype virus was found to have a higher genomic variability than its synthetic strains. It is known that the population of viral variants is important for its fitness ; thus, this analysis demonstrates an approach for connecting viral fitness to the structure of its population. Title: Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns", "Passage: directed evolution of a replicative Thermococcus polymerase . Though several point mutations were necessary to finally generate these converting enzymes , the findings may implicate the natural evolution of such enzyme activities, which would undermine a solely XNA-based firewall. This would make the integration in a single organism of additional xenobiotic \"firewall levels\" , like altered genetic codes, mandatory. However, even synthetic \"xenoorganisms\" that would show complete and durable genetic isolation from DNA-based life forms might still interact with native organisms on an ecological level, i.e. by changing habitats , food webs or by competing out native populations. Such indirect Title: Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns", "Passage: Giving an unequivocal definition of synthetic biology is challenging, even to the various actors in the field and references therein). Rather than constituting a strictly defined field, synthetic biology may be best described as an engineering-related approach to rationally design and construct biological compounds, functions and organisms not found in nature, or to redesign existing biological parts and systems to carry out new functions. It integrates different scientific disciplines, including molecular and systems biology, chemistry, physics, computer-aided modeling and design as well as an engineering-based notion of generating and using interchangeable \"biological parts\" . Compared to \"traditional\" genetic engineering, which Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Evolution is stepwise and accrues mutations gradually over time, whereas synthetic constructs would typically use a known backbone and introduce logical or targeted changes instead of the randomly occurring mutations that are present in naturally isolated viruses such as bat CoV RaTG13. In our view, there is currently no credible evidence to support the claim that SARS-CoV-2 originated from a laboratory-engineered CoV. It is more likely that SARS-CoV-2 is a recombinant CoV generated in nature between a bat CoV and another coronavirus in an intermediate animal host. More studies are needed to explore this possibility and resolve the natural origin", "Title: Tight junctions in pulmonary epithelia during lung inflammation\nPassage: The airways can be subdivided into a conducting and a respiratory region. The conducting airways comprise the cartilaginous airways from the trachea to the 10th generation of the bronchial tree, and the non-cartilaginous airways of the small bronchi to the terminal bronchioles until the 16th generation. Generations 17 to 23 are considered as respiratory airways, which finally end in the alveoli . The conducting airways ensure the humidification of inhaled air, sensing of irritants, trapping of inhaled particulate noxae and their removal from the surface of airways by mucocilliary clearance. The airways are lined by a pseudo-stratified columnar ciliated epithelium. Title: Establishment of a Reverse Genetics System for Studying Human Bocavirus in Human Airway Epithelia", "Passage: The airway epithelium, a ciliated pseudo-stratified columnar epithelium, represents the first barrier against inhaled microbes and actively prevents the entry of respiratory pathogens. It consists of ciliated cells, basal cells and secretory goblet cells that together with the mucosal immune system, provide local defense mechanisms for the mucociliary clearance of inhaled microorganisms . The polarized ciliated primary HAE, which is generated by growing isolated tracheobronchial epithelial cells at an ALI for on average one month, forms a pseudo-stratified, mucociliary epithelium and displays morphologic and phenotypic characteristics resembling those of the in vivo human cartilaginous airway epithelium of the lung . Title: Key mechanisms governing resolution of lung inflammation", "Passage: In the airways, the trachea, combined with main bronchi, constitute proximal cartilaginous airways and are responsible for the conduction of inhaled air. During breathing, the proximal pseudostratified epithelium participates in defence against environmental toxins and invading microorganisms. Conversely, a more columnar epithelium is located in distal airways, where high numbers of goblet and ciliated epithelial cells are situated. Goblet epithelial cells secret mucous, which provides lubrication to assist ciliated epithelial cells in sweeping microorganisms, dust particles and effete cells away from the lungs . The microvascular pulmonary endothelium and epithelial lining of the alveoli form the foundation of the gas Title: Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia", "Passage: The following criteria were used to quantify GFP + airway cells: because mouse lungs exhibit monopodial airway branching and these airways lack cartilage or glands, they are anatomically defined as bronchioles. Accordingly, we anatomically segregated bronchiolar airways into two groups based on morphologically distinct sites/sizes. The right or left main bronchus was categorized as large airways. Small bronchiole airways were defined as being a terminal airway of similar size.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: . Table 1 summarizes the benefits and concerns of each of the virus-vectored vaccines discussed here. Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research\nPassage: Participants with serious health conditions were concerned that the vaccine would impact on these conditions or interact with other medications . Pregnant women pointed out that the use of the vaccine during pregnancy contradicted usual advice to avoid medication during pregnancy . For this group, the lack of data about potential side effects to the foetus was of particular concern . In other studies, participants referred to a lack of information about the vaccine components , or they were concerned about specific components such as the adjuvants used in some of the pandemic vaccines . While there was most concern Title: Pre-existing immunity against vaccine vectors \u2013 friend or foe?", "Passage: However, before vectored vaccines can be used in the human population they need to satisfy several important criteria. Safety is a major concern, as even a low level of toxicity is unacceptable . Secondly, a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost, and this is particularly important in resource-poor countries . Similar constraints apply to veterinary vaccines, with cost often an even more important consideration. Finally, long-lasting cellular and humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose . Title: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research", "Passage: Study participants were particularly concerned about the vaccine's potential side-effects. Some of this concern reflected a scepticism to vaccines in general , but was in large part tied to concerns around the novelty of this particular vaccine and the speed in which it had been developed and approved .", "Title: Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus\nPassage: Interferons act as potent inhibitors of EBOV as has been proved through in vitro studies conducted involving various types of cells. IFN-\u03b2-1a treatment protected mice against a lethal challenge of EBOV . The virus clearance from the blood stream is enhanced by IFN \u03b2-1a leading to resolution of the symptoms of the disease at an early stage . Even though there is increased therapeutic usage of IFNs, but certain side effects are also associated with such treatment, viz., fever and myalgia, which must be kept in mind while opting for their use. Moreover, the occurrence of malaria additionally should be Title: Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity", "Passage: Activating natural host defense to prevent establishment and dissemination of viral infection is a valuable alternative strategy to antiviral drugs that specifically target viral processes. Interferon therapy has been used in the clinic for over two decades and has proven effective in the treatment of certain viral infections, mainly Hepatitis B and Hepatitis C , as well as malignancies and autoimmune diseases . However, IFN therapy is also associated with significant side effects that limit its use . PolyI:C, another dsRNA immune modulator, is also being tested in vitro and in vivo and has demonstrated efficacy against respiratory infections . Title: Interferon-\u03b3 Inhibits Ebola Virus Infection", "Passage: These in vivo studies suggest that IFN\u03b3 may serve as an effective prophylactic and/or therapeutic drug against EBOV infection. Several different IFNs are currently FDA approved to treat a variety of infections and autoimmune disorders. Type I IFNs have been used clinically as therapeutics against both hepatitis B and C infections , but showed mixed efficacy against EBOV infection in NHPs . The antiviral effects of IFN\u03b3 are less well-studied, but this protein is a FDA-approved therapy for chronic granulomatous disease and osteopetrosis . Chronic granulomatous patients receive IFN\u03b3 three times weekly to prevent infections, which can serve as life-long Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "Passage: Many interferons from the three classes have been tested for their antiviral activities against SARS-CoV both in vitro and in animal models. Interferon \u03b2 has consistently been shown to be the most active, followed by interferon \u03b1. The use of corticosteroids with interferon alfacon-1 appeared to have improved oxygenation and faster resolution of chest radiograph abnormalities in observational studies with untreated controls. Interferon has been used in multiple observational studies to treat SARS-CoV and MERS-CoV patients . Interferons, with or without ribavirin, and lopinavir/ritonavir are most likely to be beneficial and are being trialed in China for 2019-nCoV. This drug", "Title: Activity of sputum p38 MAPK is correlated with airway inflammation and reduced FEV(1) in COPD patients\nPassage: Mitogen-activated protein kinases play a key role in chronic inflammation, and several complex enzyme cascades have been defined. One of these, the p38 MAPK pathway, is activated by cellular stress and regulates the expression of inflammatory cytokines, including CXCL8, TNF-a and MMPs . Four isoforms of p38 MAPK family exist. Usually, p38 MAPKs are activated by phosphorylation on Thr180 and Tyr182 in the Thr-Gly-Tyr motif of the activation loop by upstream MAPK kinases MKK3 and MKK6, which are in turn activated by the MAPK kinase kinases . Once activated, p38 MAPKs effectively act on several downstream kinases, such as MAPK-activated Title: Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-\u03baB/MAPK Signaling Pathways", "Passage: Total proteins from RAW 264.7 cells were extracted in TNN buffer supplemented with protease inhibitors , 1 mg/mL aprotinin, 1 mg/mL leupeptin, and 1 mmol/L Na 3 VO 4 ) and quantified using the Bradford method. Protein samples were separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. After blocking nonspecific antibody binding sites, the membrane was incubated overnight at 4 C with mouse monoclonal antibodies against iNOS, extracellular signal-regulated kinase , phosphorylated ERK , c-Jun N-terminal kinase , pJNK, p38, p-p38, IkB-a, pIkB-a, and GAPDH. After incubation with peroxidase-conjugated secondary antibodies at 37 C for Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1", "Passage: Western blot was done as described . Equal amounts of protein were separated by 10% SDS-PAGE, electroblotted onto nitrocellulose membranes , and followed by probing with specific antibod-ies for Actin, MKP-1 , phospho-p38 MAPK, phospho-ERK1/2 . After three washes, the membranes were incubated with the corresponding secondary antibodies. The bands were detected using the Enhanced Chemiluminescence System as per the manufacturer's instructions. Title: A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1\nPassage: Western blot was done as described . Equal amounts of protein were separated by 10% SDS-PAGE, electroblotted onto nitrocellulose membranes , and followed by probing with specific antibod-ies for Actin, MKP-1 , phospho-p38 MAPK, phospho-ERK1/2 . After three washes, the membranes were incubated with the corresponding secondary antibodies. The bands were detected using the Enhanced Chemiluminescence System as per the manufacturer's instructions.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: NDV has also been explored as a vaccine vector for humans. Two NHP studies assessed the immunogenicity and efficacy of an rNDV expressing the HA or NA of A/Vietnam/1203/2004 . Intranasal and intratracheal delivery of the rNDV-HA or rNDV-NA vaccines induced both serum and mucosal antibody responses and protected from HPAIV challenge . NDV has limited clinical data; however, phase I and phase I/II clinical trials have shown that the NDV vector is well-tolerated, even at high doses delivered intravenously . While these results are promising, additional studies are needed to advance NDV as a human vaccine vector for influenza. Title: Viral vector-based influenza vaccines", "Passage: one single study, cross-reactive cellular immune responses against A viruses were observed after vaccination with a NDV-H5 construct. 168 The immunogenicity of recombinant NDV expressing the HA and NA genes of influenza virus A/Vietnam/1203/04 was tested in non-human primates. Both constructs induced VN and local IgA antibody responses and afforded protection from A challenge infection. 169, 170 Small numbers of clinical trials have been performed with NDV, which showed that the vector is well tolerated. Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics", "Passage: Human challenge studies with HRV have been shown to produce infection in over 90% of serologically susceptible subjects and result in a clinical syndrome that is comparable to that reported with natural colds . Symptoms usually appear within 24 hours and peak at 48-72 hours after inoculation. Virus shedding follows a pattern similar to that of their symptoms. In recent times, several hundred inoculations of adult subjects have been reported and have established this as a safe and effective method in which to study HRV-related disease in both healthy and asthmatic subjects . Title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics\nPassage: Pirodavir an intranasal capsid-binding molecule reached phase 3 clinical trials for HRV prevention and treatment in the 1990s. Although the compound decreased viral replication and shedding, it failed to show a significant reduction in the duration or severity of symptoms .", "Title: Advances in Directly Amplifying Nucleic Acids from Complex Samples\nPassage: Nucleic acid amplification tests have become indispensable tools in biology and medicine. For example, for infectious diseases diagnostics, NAATs are generally faster, more sensitive, and more specific than the current gold standard of culture-based techniques. In fact, a number of DNA-and RNA-based diagnostics are now recommended by the US Food and Drug Administration for infectious diseases such as human immunodeficiency virus . Bringing NAATs to the point of care , and particularly to resource-poor settings, is envisioned to revolutionize healthcare. Unfortunately, many NAATs require access to expensive, specialized equipment and a degree of expertise that is highly unlikely to be Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings", "Passage: An accurate and rapid diagnostic test can facilitate better patient care by informing prompt and appropriate treatment, leading to decreased morbidity and mortality while saving money and preventing improper use of antimicrobial drugs . Rapid diagnostics are also critical to identify pathogens for which targeted public health interventions can be employed to control disease transmission in the community. Nucleic acid amplification technologies to identify common pathogens have become a routine approach for infectious disease diagnosis in high-income countries. Many NAAT products now exist that have been cleared or approved by national health authority agencies, in addition to a variety of Title: Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings", "Passage: qualified laboratory-developed methods used in some facilities . Although various amplification methodologies have been developed, RT-PCR is the predominant NAAT used for diagnostic testing . The implementation of NAAT in clinical diagnostic laboratories is complex and can require sophisticated equipment, infrastructure, skilled laboratorians, and a robust quality management program . These requirements present insurmountable challenges when trying to diagnose infectious diseases in the resource limited settings of low and middle-income countries , especially in rural environments where operational and logistical limitations further challenge implementation . Patients with communicable diseases in these locations would greatly benefit from rapid on-site diagnosis and Title: Advances in Directly Amplifying Nucleic Acids from Complex Samples", "Passage: Direct NAATs are advantageous when complicated, costly laboratory apparatuses are not available. They not only reduce the time, labor, and technical constraints of molecular testing, but also bring the additional benefit of standardizing results . Indeed, a growing number of groups are developing such \"direct\" NAATs. Most notably, the Alere i Influenza A&B assay became the first FDA Clinical Laboratory Improvement Amendments -waived nucleic acid-based test in January 2015. As the Alere i system requires no front-end nucleic acid extraction, and can be used outside of traditional laboratory sites , its development and CLIA-waived status provide strong support for further", "Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity\nPassage: The antiviral activities of gemcitabine against the abovementioned viruses are summarized in Table 1 . MERS-CoV and SARS-CoV belong to the family of Coronaviridae and are causative agents of severe viral respiratory illness in humans. To efficiently select appropriate antiviral drug candidates, Dyall et al. screened 290 FDA-approved drugs in virus-infected Vero E6 cells and identified gemcitabine as one of drugs with antiviral activity against both MERS-CoV and SARS-CoV . More recently, gemcitabine was shown to effectively suppress ZIKV infection and replication in human retinal pigment epithelium cells, particularly at non-cytotoxic concentrations . ZIKV, a member of the Flaviviridae family, Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: Gemcitabine is a cytidine analog that has been clinically used for the treatment of various cancers . However, in recent years, the antiviral activity of gemcitabine has also been reported against a broad range of RNA viruses, including Middle East respiratory syndrome coronavirus , severe acute respiratory syndrome coronavirus , Zika virus , HCV, poliovirus , influenza A virus , HIV, and enteroviruses . Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: Gemcitabine is a cytidine analog that has been clinically used for the treatment of various cancers . However, in recent years, the antiviral activity of gemcitabine has also been reported against a broad range of RNA viruses, including Middle East respiratory syndrome coronavirus , severe acute respiratory syndrome coronavirus , Zika virus , HCV, poliovirus , influenza A virus , HIV, and enteroviruses . Title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity", "Passage: HIV infectivity by increasing the viral mutation frequency . In a follow up study, Clouser et al. further reported the antiviral effect of gemcitabine against HIV-related retrovirus, murine leukemia virus , in vitro and even in murine AIDS model . A significant antiviral effect of gemcitabine on IAVs was also reported for RPE cells by Denisova et al. . They also tested whether gemcitabine had an antiviral effect on several other viruses of different families and found its strong inhibitory effect on Sindbis virus and herpes simplex virus-1 but relatively weak effects on Semliki forest virus and human echovirus 6,", "Title: Genetic Analysis of West Nile Virus Isolates from an Outbreak in Idaho, United States, 2006\u20132007\nPassage: The results for the presence of ID-\u039413 deletions in the 3\u2032UTR are shown in Table 1 . All samples that had amplicon patterns corresponding to deletions were sequenced to confirm the PCR results . Out of 31 specimens from Idaho from 2006-2007, 18 had the ID-\u039413 deletion. The ID-\u039413 deletion was also found in one human isolate from North Dakota in 2006, but not in any isolate from other states included in this study. In addition, a deletion of 3 nt was identified in a Colorado isolate, CO4-07. These deletions and insertion are placed within ~100 bp of the variable Title: Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential", "Passage: Very few small sequence variants were identified in NF54 compared to the 3D7 reference; 17 nonsynonymous mutations were present in 15 single-copy non-pseudogene-encoding loci . Short indels were detected in 185 genes; many of these indels had a length that is not multiple of three and occurred in homopolymer runs, possibly representing remaining PacBio sequencing error. However, some may be real, as a small indel causing a frameshift in PF3D7_1417400, a putative protein-coding pseudogene that has previously been shown to accumulate premature stop codons in laboratory-adapted strains , and some may be of biologic importance, such as those seen in Title: Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters", "Passage: strain. There are also 26 amino acid differences in the L gene between the two strains. Finally, although deletion of the hMPV M2-2 ORF succeeded in attenuating both hMPV strains, the CAN97-83\u0394M2-2 virus was more attenuated in hamsters than rhMPV/\u0394M2-2 . Clearly there are differences between the CAN97-83 and hMPV/NL/1/ 00 strains. Further study will be required to elucidate the differences in phenotype. Title: Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential", "Passage: Assemblies were compared to the 3D7 reference using MUMmer's nucmer , and the showsnps function was used to generate a list of SNPs and small indels between assemblies. Coding and noncoding variants were classified by comparing the show-snps output with the 3D7 gff3 file using custom scripts. For a subset of genes which are discussed specifically below , small variants were confirmed through manual inspection of extracted sequence alignments using clustal omega . Structural variants, defined as indels, deletions, and tandem or repeat expansion and contractions each greater than 50 bp in length were identified using the nucmer-based Assemblytics tool", "Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: There are also rumours that the SARS-CoV-2 was artificially, or intentionally, made by humans in the lab, and this is highlighted in one manuscript submitted to BioRxiv , claiming that SARS-CoV-2 has HIV sequence in it and was thus likely generated in the laboratory. In a rebuttal paper led by an HIV-1 virologist Dr. Feng Gao, they used careful bioinformatics analyses to demonstrate that the original claim of multiple HIV insertions into the SARS-CoV-2 is not HIV-1 specific but random . Because of the many concerns raised by the international community, the authors who made the initial claim have already Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Currently, there are speculations, rumours and conspiracy theories that SARS-CoV-2 is of laboratory origin. Some people have alleged that the human SARS-CoV-2 was leaked directly from a laboratory in Wuhan where a bat CoV was recently reported, which shared \u223c96% homology with the SARS-CoV-2 . However, as we know, the human SARS-CoV and intermediate host palm civet SARSlike CoV shared 99.8% homology, with a total of 202 single-nucleotide variations identified across the genome . Given that there are greater than 1,100 nt differences between the human SARS-CoV-2 and the bat RaTG13-CoV , which are distributed throughout the genome in a Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2", "Passage: Another claim in Chinese social media points to a Nature Medicine paper published in 2015 , which reports the construction of a chimeric CoV with a bat CoV S gene in the backbone of a SARS CoV that has adapted to infect mice and is capable of infecting human cells . However, this claim lacks any scientific basis and must be discounted because of significant divergence in the genetic sequence of this construct with the new SARS-CoV-2 . Title: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2\nPassage: Text: The emergence and outbreak of a newly discovered acute respiratory disease in Wuhan, China, has affected greater than 40,000 people, and killed more than 1,000 as of Feb. 10, 2020. A new human coronavirus, SARS-CoV-2, was quickly identified, and the associated disease is now referred to as coronavirus disease discovered in 2019 .", "Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020\nPassage: influenza and other diseases in Europe may be expanded for this purpose. In addition, a number of countries in Europe are adapting and, in some cases, already using existing sentinel primary care based surveillance systems for influenza to detect community transmission of SARS-CoV-2. This approach will be used globally to help identify evidence of widespread community transmission and, should the virus spread and containment no longer be deemed feasible, to monitor intensity of disease transmission, trends and its geographical spread. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: On 27 January 2020, the European Centre for Disease Prevention and Control and the WHO Regional Office for Europe asked countries to complete a WHO standard COVID-19 case report form for all confirmed and probable cases according to WHO criteria . The overall aim of surveillance at this time was to support the global strategy of containment of COVID-19 with rapid identification and follow-up of cases linked to affected countries in order to minimise onward transmission. The surveillance objectives were to: describe the key epidemiological and clinical characteristics of COVID-19 cases detected in Europe; inform country preparedness; and improve further Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: With increasing numbers of cases in Europe, data from surveillance and investigations in the region can build on the evidence from countries in Asia experiencing more widespread transmission particularly on disease spectrum and the proportion of infections with severe outcome . Understanding the infection-severity is critical to help plan for the impact on the healthcare system and the wider population. Serological studies are vital to understand the proportion of cases who are asymptomatic. Hospital-based surveillance could help estimate the incidence of severe cases and identify risk factors for severity and death. Established hospital surveillance systems that are in place for", "Title: Activity of sputum p38 MAPK is correlated with airway inflammation and reduced FEV(1) in COPD patients\nPassage: Diffuse persistent inflammation in the airway is one of the key pathologic features of COPD. Together with proteases and oxidant stimuli, which directly affect lung structures, inflammatory cells actively participate in the pathogenesis of the disease and promote biochemical reactions that result in progressive alteration and remodeling of the lower airways. Typically, neutrophil recruitment to the airways is induced by chemotactic factors like CXCL8 and leukotriene B4 in COPD patients. Title: Key mechanisms governing resolution of lung inflammation", "Passage: Affecting approximately 10 % of UK adults, asthma is a common disorder of multi-factorial origins, with research indicating that both genetics and the environment have a significant role to play. In predisposed individuals, 'normal' environmental antigens transmigrate through the airway epithelia and are presented to na\u00efve T cells, which trigger activation of IgE production by B cells. IgE interacts with receptors on the surface of tissue resident mast cells, and further exposure to the antigen results in IgE cross-linkage with cell activation. The resultant mast cell degranulation causes release of mediators including histamine, LTB 4 , IL-8 and IL-10 and Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: specific mediators to facilitate viral targeting and clearance, including type II interferon , IL-2, IL-4, IL-5, IL-9, and IL-12 . These factors heighten local inflammation and the infiltration of granulocytes, T-cells and B-cells . The increased inflammation, in turn, worsens the symptoms of airway diseases. Title: Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium", "Passage: of tight junction increasing the leakiness further augments the inflammation and exacerbations. In addition, viral infections are usually accompanied with oxidative stress which will further increase the local inflammation in the airway. The dysregulation of inflammation can be further compounded by modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation. Finally, the change in the local airway environment and inflammation promotes growth of pathogenic bacteria that may replace the airway microbiome. Furthermore, the inflammatory environment may also disperse upper airway commensals into the lower airway, further causing inflammation and alteration of", "Title: MERS coronavirus: diagnostics, epidemiology and transmission\nPassage: Some sero-assays have bypassed the risks of working with infectious virus by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins , or using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase . A pseudo particle neutralization assay has seen widespread used in animal studies and was at least as sensitive as the traditional microneutralization test. ] Studies using small sample numbers and ppNT found no evidence of MERS-CoV neutralizing antibody in sera from 158 children with LRT infections between May 2010 and May 2011, 110 sera from 19 to 52 year old male blood Title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera", "Passage: lysates may lead to cross-reactivity, resulting in reduced specificity . High quality filovirus recombinant protein antigens can be safely prepared without the need for high BSL-4 biocontainment facilities and outside EBOV endemic areas. Their use in ELISA has potential to reduce the risk of false positive results and allows for better standardization . Testing clinical specimens potentially containing a BSL-4 viral agent presents a serious biohazard. While a number of inactivation methods were shown to completely inactivate EBOV , they also markedly alter the protein components in human blood, e.g., enzymes and coagulation factors . Results of viral inactivation protocols Title: Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers", "Passage: or luciferase has also been developed. We have recently developed a VSV-based pseudotype bearing Lassa virus GP for the detection of neutralizing antibodies in the sera obtained from a Lassa fever patient. An example of the LASV neutralization assay using the VSV pseudotype is shown . In the presence of serum from Lassa fever patients, the number of GFP-positive cells is significantly reduced compared with the number in the absence of the patient's serum . The control VSV pseudotype bearing VSV GP is not neutralized by any sera. When the cut-off serum dilution is set at 50% inhibition of infectivity Title: Assay Challenges for Emerging Infectious Diseases: The Zika Experience\nPassage: avoidance of cross-reactivity is more easily engineered into molecular tests of virus RNA because primers or probes can be designed to be virus-, antigen-and serotype-specific , it is not as easily achieved for immunoassays .", "Title: Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes\nPassage: We emphasize that the mechanism for microbiome-based modulation of immune responses described herein is based on sequence homology between specific microbiome sequences and potential epitope sequences from allergens, pathogens or autoantigens. As such, this is different and distinct from other general means by which the microbiome has been described to modulate immune responses. Bacteria present in the microbiome secrete soluble factors and metabolites and these bioactive compounds affect the function of intestinal epithelium and mucosal immune cells, resulting in production of cytokines and related factors . Microbiome antigens and metabolites have been proposed to induce peripherally derived regulatory T cells. Title: Influence of H7N9 virus infection and associated treatment on human gut microbiota", "Passage: Remarkably, chronic complex diseases have been associated with gut microbiota. Although the intestinal microbiota is generally stable in healthy individuals over long periods of time, antibiotics can significantly reshape the gut microbiota, allowing exogenous microbes to outgrow commensal bacteria and cause permanent changes in varying states of disease 6, 11, 12 . Probiotic agents, which beneficially affect the host by improving the gut microbial balance, have been used for the prevention and treatment of respiratory tract diseases to avoid bacterial translocation 13, 14 . It is noteworthy that gastrointestinal distress symptoms were observed in some of our recently reported cases Title: What Have We Learned about the Microbiomes of Indoor Environments?", "Passage: Exposures to the \"right\" number of the \"right\" kinds of microbes may be beneficial for human health. Last, after decades of indoor microbiology research focusing primarily on human exposure to infectious agents and asthma/allergy triggers that yield adverse health outcomes, evidence is emerging that some measures of microbial diversity and/or abundance in indoor environments may actually be beneficial for human health. For example, Fujimura et al. demonstrated that mice exposed to dog-associated house dust had a distinct gut microbiome composition and were protected against airway allergen challenges . Dannemiller et al. found that in human populations, lower fungal diversity Title: Back to the future in a petri dish: Origin and impact of resurrected microbes in natural populations", "Passage: partially purified, and frozen fecal microbiota . FMT proved, for instance, to be a highly effective therapy for recurrent Clostridium difficile infections, whose incidence and severity have increased markedly since the 1990s, with frequent failure of standard antibiotic treatments . Despite their efficiency and their high therapeutic potential, FMT should be used with caution, as we still have little perspective on their long-term effects . Beyond the evident risk of pathogens transmission, which can be limited by an attentive screening of stool samples , FMT may have unexpected side effects, such as the stimulation of chronic diseases or behavioral disorders", "Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold\nPassage: an anti-IgE antibody elicited antibodies that bound purified IgE molecules , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. For example, immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes . Phage displaying or chemically Rubinchik and Chow conjugated to sperm antigen peptides or peptide mimics and gonadotropin-releasing hormone are also in development. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: an anti-IgE antibody elicited antibodies that bound purified IgE molecules , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. For example, immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes . Phage displaying or chemically Rubinchik and Chow conjugated to sperm antigen peptides or peptide mimics and gonadotropin-releasing hormone are also in development. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: pIII-scFv fusion protein elicited stronger humoral and cell-mediated immune responses than DNA encoding the scFv alone , suggesting that under some circumstances, endogenous phage T-cell epitopes can enhance the immunogenicity of associated proteins. Taken together, the results of these studies show that as a particulate virus-like particle, the filamentous phage likely triggers different types of immune responses than recombinant protein antigens, and provide additional T-cell help to displayed or conjugated proteins. However, the low copy number of pIII-displayed proteins, as well as potentially unwanted phage-associated adjuvanticity, can make display of recombinant proteins by phage a suboptimal vaccine choice. Title: Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold", "Passage: pIII-scFv fusion protein elicited stronger humoral and cell-mediated immune responses than DNA encoding the scFv alone , suggesting that under some circumstances, endogenous phage T-cell epitopes can enhance the immunogenicity of associated proteins. Taken together, the results of these studies show that as a particulate virus-like particle, the filamentous phage likely triggers different types of immune responses than recombinant protein antigens, and provide additional T-cell help to displayed or conjugated proteins. However, the low copy number of pIII-displayed proteins, as well as potentially unwanted phage-associated adjuvanticity, can make display of recombinant proteins by phage a suboptimal vaccine choice.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: The structural proteins are provided in cell culture production systems. One important feature of the replicon systems is the self-replicating nature of the RNA. Despite the partial viral genome, the RNAs are self-replicating and can express transgenes at very high levels . Title: Packaging of Genomic RNA in Positive-Sense Single-Stranded RNA Viruses: A Complex Story", "Passage: Nugent and co-workers used a replication-competent poliovirus RNA to investigate whether RNA replication by an active RdRp is required for selective packaging . This RNA had deletions in the capsid gene ; thus, it could only be packaged in the presence of an RNA that contains the structural proteins . A replicon is an RNA that has all the genes required for replication. A helper RNA provides the structural proteins required to package the replicon RNA. Furthermore, in these experiments the replicon cannot be replicated in the presence of guanidine, while replication of the helper RNA is insensitive to this Title: Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology", "Passage: the development of highly sensitive, cell-based reporter assays , eliminates the problem of compound fluorescence , and possesses several advantages such as high reliability, convenience and adaptability to HTS assays. Remarkably, primary HTS followed by validation using traditional assays based on the parental viruses will greatly aid the discovery of novel antivirals against infectious diseases. Finally, the use of replicons or pseudoparticles would help to identify the step of the viral life cycle as the potential targets of antivirals. Title: Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology\nPassage: With the development of reverse genetics systems, RCREVs provide an ideal tool for monitoring the dynamics of viral infection progression in vitro and in vivo due to eliminating the need for secondary labeling, which represents a significant advance in the study of the biology of viruses .", "Title: Can\u2019t RIDD off viruses\nPassage: IRE1 and RNaseL, in addition to biochemical similarities in protein kinase domain and structural similarities in their RNase domain, share the functional consequences of their activation in initiating cellular apoptosis through JNK signaling . Though initial discoveries were made in the context of homeostatic and anti-viral role for the former and latter, differences between the pathways are narrowed by further advances in research. In the same vein, while inhibition of IRE1 signaling in virus infected cells indicates a potential anti-viral role, www.frontiersin.org Nature of RNase substrates Both 28S rRNA and mRNAs IRE1\u03b2 can cleave both 28S rRNA and mRNA while Title: Can\u2019t RIDD off viruses", "Passage: IRE1 and RNaseL, in addition to biochemical similarities in protein kinase domain and structural similarities in their RNase domain, share the functional consequences of their activation in initiating cellular apoptosis through JNK signaling . Though initial discoveries were made in the context of homeostatic and anti-viral role for the former and latter, differences between the pathways are narrowed by further advances in research. In the same vein, while inhibition of IRE1 signaling in virus infected cells indicates a potential anti-viral role, www.frontiersin.org Nature of RNase substrates Both 28S rRNA and mRNAs IRE1\u03b2 can cleave both 28S rRNA and mRNA while Title: Can\u2019t RIDD off viruses", "Passage: In fact, exogenous over-expression of IRE1 in mammalian cells lead to activation suggesting that, under homeostatic conditions, the non-juxtaposition of cytosolic domains maintains an inactive IRE1 . Once activated, IRE1 performs cleavage of a variety of RNA substrates mediated by its RNase domain, in addition to phosphorylating and thereby activating JNK . Depending on the RNA substrate, the cleavage catalyzed by IRE1 RNase produces differential consequence. Although scission of the Xbp1 mRNA transcript at two internal positions is followed by splicing of the internal segment through ligation of the terminal cleavage products, that in all other known IRE1 target RNA Title: Can\u2019t RIDD off viruses", "Passage: In fact, exogenous over-expression of IRE1 in mammalian cells lead to activation suggesting that, under homeostatic conditions, the non-juxtaposition of cytosolic domains maintains an inactive IRE1 . Once activated, IRE1 performs cleavage of a variety of RNA substrates mediated by its RNase domain, in addition to phosphorylating and thereby activating JNK . Depending on the RNA substrate, the cleavage catalyzed by IRE1 RNase produces differential consequence. Although scission of the Xbp1 mRNA transcript at two internal positions is followed by splicing of the internal segment through ligation of the terminal cleavage products, that in all other known IRE1 target RNA", "Title: Circulating microRNAs in malaria infection: bench to bedside\nPassage: MiRNA was firstly extracted from Caenorhabditis elegans tissues . It is short nucleotides with 18-25 single-stranded RNA . The miRNA genes are located mainly in the non-coding region of the genome and are firstly transcribed to primary microRNAs . The miRNA was a synthesis in the nucleolus/cytoplasm and some released from apoptotic cells . The early studies on miRNAs were done using organ or biopsy tissue. The limitation of testing may relate to tissue type, volume and extraction method. The discovery of miRNAs as promising disease biomarkers either in the blood or plasma was a breakthrough . Title: Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection", "Passage: In contrast to siRNAs, microRNAs do not require perfect complementarity to their target RNA molecule , which mitigates the effect of mutations in the RNA genome and facilitates a similar function across multiple forms of FMDV. Another key difference between siRNAs and miRNAs is that siRNAs are generally produced from exogenous RNA molecules, while miRNAs are generated from endogenous RNA molecules . In the normal cellular environment, miRNAs act as key posttranscriptional regulators of gene expression for a variety of biological processes including immune response, cell proliferation, and metabolism . Title: H5N1 influenza virus-specific miRNA-like small RNA increases cytokine production and mouse mortality via targeting poly(rC)-binding protein 2", "Passage: Our results demonstrated that upon virus infection, the biogenesis of miR-HA-3p in the host cells followed an atypical miRNA biogenesis pathway. Although miR-HA-3p is derived from the coding region of viral HA segment, its maturation is independent of Dicer and Drosha. Northern blot analysis of various pre-miR-HA-3p mutants indicated that the biogenesis of miR-HA-3p is dependent on the unique hairpin structure of pre-miR-HA-3p. Like Dengue virus-encoded miRNA-like DENV-vsRNA-5 recently reported by Mazhar and Sassan , the maturation process from pre-miR-HA-3p to miR-HA-3p in the host cells is not due to RNA random degradation but is dependent on Ago2. The biogenesis Title: H5N1 influenza virus-specific miRNA-like small RNA increases cytokine production and mouse mortality via targeting poly(rC)-binding protein 2", "Passage: MicroRNAs belong to the category of single-stranded small RNAs that can inhibit the expression of specific mRNAs via binding to complementary sequences within the target mRNAs . To date, over 250 viral miRNAs have been identified, and almost all of them are encoded by DNA viruses or retroviral RNA viruses . Thus, the lack of viral miRNAs encoded by RNA virus has led many to infer that normal viruses with RNA genomes are not amenable to the exploitation of miRNA pathway because processing of the hairpin would result in the degradation of the viral RNA genome and mRNAs . However,", "Title: Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo\nPassage: relies on the rapid IV injection of a comparably large volume . Alternative strategies for the application of naked siRNAs include various delivery routes which, however, often provide an only local administration or rely on an administration at least close to the target tissue or target organ, thus restricting the number of target organs which may not be relevant for certain diseases. It should also be noted that several studies described here and below use rather large amounts of siRNAs and that upon intravenous injection of siRNAs the liver is the primary site of siRNA uptake. As an alternative approach Title: Delivery Systems for Intradermal Vaccination", "Passage: ID delivery can also be achieved via jet injection or particle injection routes, which are needle-free methods of vaccine and drug delivery. There have been decades of clinical experience with jet injection, and more recent studies are being conducted with newer innovations in this technology. Title: Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo", "Passage: In the last years, a large body of studies has been published which describe different strategies for the systemic or local application of siRNAs in vivo. Tables 1-3 give an overview. The probably largest number of papers focuses the use of unmodified siRNAs whose administration is often performed IV by hydrodynamic transfection . While this method is widely used and in some cases led to efficient target gene inhibition in the liver and, to a lesser extent, in lung, spleen, pancreas, and kidney, it may suffer from certain technical and practical limitations at least in a therapeutical setting since it Title: Delivery Systems for Intradermal Vaccination", "Passage: As a simpler, albeit probably less efficient, method, microneedles can be used to pierce the skin to make it more permeable and thereby enable entry of topically applied vaccines. This method is attractive because the micro-scale pores made by microneedle insertion are generally too small for penetration of microorganisms , yet large enough for delivery of sub-unit and possibly viral vaccines. After insertion and removal of the microneedles, vaccine can be applied using a patch or other topical formulation for slow delivery by diffusion through long-lived pores . This approach was investigated for transcutaneous vaccination using diphtheria toxoid and influenza", "Title: Hantaviruses in the Americas and Their Role as Emerging Pathogens\nPassage: N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences . N is also reported to interact with actin microfilaments, and the SUMO-1 protein . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in Title: High Fidelity Processing and Activation of the Human \u03b1-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3", "Passage: Although the junctional sequences recognized by NE, PR3, and CG in His 6 -proHNP1 are identical to those in the natural precursor, we questioned whether the 41-residue extension of the proHNP-1 sequence resulting from the hexa-His and DDDDK tags and spacer sequences might alter protease interactions with the target. To test this, we produced proHNP1 without the Nterminal tag by incubating proHNP1A with enterokinase, thereby releasing the 41-residue tag sequence. This peptide was then treated with NE, PR3, or CG which liberated peptides with monoisotopic masses of 3439.7, 3439.7 and 3684.5 A.M.U., respectively, products equivalent to those generated from His Title: High Fidelity Processing and Activation of the Human \u03b1-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3\nPassage: 6 -proHNP1A. Thus the 41-residue N-terminal fusion tag did not alter the specificity of cleavage of proHNP1A by NE, PR3, or CG. Title: Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses", "Passage: an inhibitor of the IFN signaling pathway, N protein acts by encapsidating the viral genomic RNA and inhibiting its recognition by RIG-I . Similar observations were made using other viral IFN antagonist proteins including Ebola virus VP35, which acts by masking viral PAMPs from cellular receptors .", "Title: The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract\nPassage: The two main cells present in the alveoli are the Type 1 and Type 2 pneumocytes. Type 1 pneumocytes are large and flattened and incapable of replication. The type 2 pneumocytes are smaller and responsible for surfactant production involved in the antiviral defence mentioned above . When type 1 cells are damaged the type 2 will differentiate into type 1 cells. The diffuse alveolar damage picture seen in the fatal cases of 1918 H1N1 and H5N1 is due to the destruction of the type 1 pneumocytes with a consequent disruption of the integrity of the vascular-epithelial interface leading to an Title: Augmented Lung Inflammation Protects against Influenza A Pneumonia", "Passage: We have recently reported that treatment with an aerosolized lysate of nontypeable Haemophilus influenzae induces profound inflammation in the lungs, yet it strongly protects mice against otherwise fatal bacterial pneumonia . The induced protective phenomenon, known as Stimulated Innate Resistance , is maximal within 4 h of treatment and does not rely on recruited neutrophils or resident mast cells and alveolar macrophages. Given the profound induction of lung inflammation by this treatment, we perceived an opportunity to determine whether host inflammation contributed to or prevented mortality in influenza A pneumonia. Title: B-1a cells protect mice from sepsis-induced acute lung injury", "Passage: Recent findings demonstrate an active role of B-1a cells for protection against lung infection caused by influenza virus . During influenza virus infection B-1a cells migrate from serosal cavities to the lungs, where they secrete natural Abs and other immunomodulatory molecules to protect rodents against influenza virus infection . Consistently, in various animal models of ALI initiated by direct instillation of LPS, E. coli or S. pneumoniae, B-1a cells were shown to migrate from the pleural cavity to the lung parenchymal tissues, where they secrete GM-CSF and IgM to protect rodents against ALI . A recent study has demonstrated that Title: Augmented Lung Inflammation Protects against Influenza A Pneumonia", "Passage: Non-typeable Haemophilus influenzae was stored, grown and harvested as described . The cell pellet was washed and resuspended in 20 ml 0.9% sodium chloride solution. This suspension was passed three times through an EmulsiFlex C5 cell disruptor at greater then 10,000 psi, then diluted to 4-5 mg/ml in 0.9% sodium chloride solution by bicinchoninic assay and centrifuged at 15,0006g for 10 min. The supernatant was collected, the protein concentration was adjusted to 2.5 mg/ml, and the lysate was sterilized by passage through a 0.2 mm filter and frozen in 8 ml aliquots at 280uC. Treatment of mice with aerosolized lysate", "Title: Estimating the number of infections and the impact of non-\nPassage: Public events Title: Estimating the number of infections and the impact of non-\nPassage: Public events Title: Estimating the number of infections and the impact of non-\nPassage: Public events Title: Estimating the number of infections and the impact of non-\nPassage: Public events", "Title: Estimating the number of infections and the impact of non-\nPassage: the appendix, and general limitations presented below in the conclusions. Title: Globalization and emerging governance modalities\nPassage: me two conclusions. Title: Estimating the number of infections and the impact of non-\nPassage: 4 Conclusion and Limitations Title: Outcome of paediatric intensive care survivors\nPassage: and, therefore, strong conclusive statements difficult.", "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review\nPassage: participants, combination of western and Chinese treatment vs. Chinese treatment in 123 participants, integrative Chinese and Western treatment in 49 patients, usage of a specific Chinese medicine in four participants and early use of corticosteroid in 16 participants. Another notable study was an open non-randomized study investigating ribavirin/lopinavir/ritonavir usage in 152 participants . One randomized controlled trial investigating integrative western and Chinese treatment during the SARS epidemic was excluded as it was a Chinese article . Title: The potential contributions of traditional Chinese medicine to emergency medicine\nPassage: could effectively control or alleviate the symptoms of the disease and prevent the disease from exacerbation. Title: Effectiveness of Integrative Therapy for Parkinson\u2019s Disease Management", "Passage: considered. This study investigated whether KM could reduce hospitalization in the management of PD patients in the South Korea. Two groups of patients, an integrative therapy group using both biomedicine and KM and a monotherapy group using only biomedicine, were compared by PS estimation and matching based on confounders such as sex, age, comorbidity, and anti-parkinsonism medication. The prevalence of hospitalization because of pneumonia/sepsis was significantly lower in the integrative therapy group than the monotherapy group. Traditional medicine may have beneficial immunomodulatory effects for preventing viral infections . For severe acute respiratory syndrome , advantages to treatment with integrative Chinese Title: Effectiveness of Integrative Therapy for Parkinson\u2019s Disease Management", "Passage: Except for patients diagnosed with PD prior to 2007, patients treated without biomedicine treatment and those younger than 65 years, a total of 1,438 patients were included in the cohort. Of these, 117 were treated using both biomedicine and Korean medicine, while 1,321 received biomedicine alone. After PS estimation and matching, the cohort used in the analysis included 228 subjects . The PS matching was considered to be well-fitted based on a c-statistics value of 0.810 and a p-value of the Goodness-of-Fit Test of 0.141. The patients' characteristics based on confounders in the two groups before and after PS matching", "Title: Host resilience to emerging coronaviruses\nPassage: patients . By understanding risk factors for disease severity we can perhaps predict if a host may be nonresilient and tailor the treatment options appropriately. Title: Host resilience to emerging coronaviruses\nPassage: DOI: 10.2217/fvl-2016-0060 Title: Host resilience to emerging coronaviruses\nPassage: Date: 2016-07-01 Title: Host resilience to emerging coronaviruses\nPassage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079962/", "Title: One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor\nPassage: Looking forward, we need to understand how NTCP interacts with both HBV envelope proteins and with other cellular proteins, especially through the motif embedded in the cell membrane. NTCP itself is not sufficient to allow HBV infection, as the majority of HepaRG cells were found to express NPCT but not to be infected . NTCP might initiate or mediate molecular interactions that can overcome the cell-surface restrictions for viral entry. Such cooperative cellular or viral factors have to be discovered and demonstrated to enhance the efficiency of viral infection, at a level comparable to a natural one . For example, Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide", "Passage: We subsequently examined the susceptibility of iNTCP cells to HBV infection. At an MOI of 6000 GEq/cell, iNTCP cells showed high susceptibility to HBV infection without DMSO treatment . This infection was significantly inhibited by PreS1 peptide treatment , which indicates that HBV infection was NTCP-mediated. Taken together, these results show that Dox-induced NTCP proteins are exposed on the cell surface and functionally interact with PreS1. Title: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide", "Passage: In this study, we generated iNTCP cells, which have high NTCP expression and high susceptibility to HBV infection, and also developed a monoclonal antibody that recognizes cell-surface NTCP. Using these tools, we identified glabridin as a compound that inhibits HBV infection by downregulating levels of its entry receptor, NTCP. Although primary hepatocytes express NTCP at low levels for the uptake of bile acids, endogenous NTCP in hepatocellular carcinoma cell lines is not sufficient to achieve successful infection with HBV in vitro. Hepatocellular carcinoma cell lines stably expressing NTCP have been created, and exhibited increased susceptibility to HBV infection , but Title: One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor", "Passage: the authors can use the NTCP-expressing cell lines as the starting materials to systemically identify other factors and make these cell lines more productive and permissive to HBV infection. In the near future, standard virological assays for HBV infections, including Northern or Western blots, are expected to demonstrate the successful HBV infections in vitro.", "Title: Viable Influenza A Virus in Airborne Particles from Human Coughs\nPassage: Cough-generated aerosols were collected using a cough aerosol particle collection system similar to that described previously. An ultrasonic spirometer measured the volume and flow rate of each cough, and a modified 10 liter piston-style mechanical spirometer served as an accumulation chamber for the cough aerosol. A stainless steel tray was attached to the piston of the mechanical spirometer to collect any large ballistic cough spray droplets that impacted the piston. Cough aerosol particles were collected using an SKC BioSampler with a 5 ml vessel containing 5 ml of viral transport media consisting of Hank's Balanced Salt Solution supplemented with 0.1% Title: Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method", "Passage: Bioaerosols are present virtually anywhere in the environment, and their exposure is shown to cause numerous adverse health effects . In addition, there is also a possible release of biowarfare agents in a man-made bio-terror event. A number of studies demonstrated that the respiratory tract can be colonized with disease organisms . Through talking, coughing, sneezing or singing, the potential virulent organisms can be exhaled and spread into the ambient environment , which accordingly causes air contamination. For example, SARS in 2003 and H1N1 in 2009 outbreaks were shown to be attributed to the airborne route of disease transmission . Title: Viable Influenza A Virus in Airborne Particles from Human Coughs\nPassage: each cough, the cough-generated aerosol was collected using the aerosol sampler. This procedure was repeated for a total of six coughs from each subject. Title: Viable Influenza A Virus in Airborne Particles from Human Coughs", "Passage: was closed and the SKC BioSampler was turned on. The cough aerosol was pulled out of the spirometer and collected by the aerosol sampler. Airborne droplets larger than about 10-15 \u00b5m collected in the sampler elbow, while smaller particles were collected in the sampler collection media. As the aerosol sampler drew air, the piston moved to the left until no air remained in the spirometer.", "Title: Pneumonia in Bhutanese children: what we know, and what we need to know\nPassage: The clinical case definition of pneumonia has been changing over the last few decades . As of today, there is no optimal gold standard definition available . Lower respiratory infections is a broad term that includes pneumonia and bronchiolitis, as defined in the Global Burden of Diseases, Injuries, and Risk Factors Study . This is the terminology we strived to use in this review. However, we will report data as defined by the study authors. Thereby, ARI is often used and may imply here a broader concept including both upper and lower respiratory infections. Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: one pre-pneumococcal conjugate vaccination study, only 34% of children hospitalized with pneumonia had primary end-point pneumonia . A revised case definition of \"presumed bacterial pneumonia\" has been introduced, and this definition includes pneumonia cases with WHO-defined alveolar consolidation, as well as those with other abnormal chest radiograph infiltrates and a serum C-reactive protein of at least 40 mg/L . This definition has been shown to have greater sensitivity than the original WHO radiologic definition of primary end-point pneumonia for detecting the burden of pneumonia prevented by pneumococcal conjugate vaccination . Using the revised definition, the 10-valent pneumococcal conjugate vaccine , Title: Community-acquired pneumonia in children \u2014 a changing spectrum of disease", "Passage: The WHO radiologic case definition was not intended to distinguish bacterial from viral etiology but rather to define a sub-set of pneumonia cases in which pneumococcal infection was considered more likely and to provide a set of standardized definitions through which researchers could achieve broad agreement in reporting chest radiographs. However, despite widespread field utilization, there are concerns regarding inter-observer repeatability. There has been good consensus for the description of lobar consolidation but significant disagreement on the description of patchy and perihilar infiltrates . In addition, many children with clinically severe lung disease do not have primary end-point pneumonia: in Title: Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia", "Passage: Pneumonia was defined as: bacterial, if microbiological investigations revealed at least one bacterium and no virus; , viral, if microbiological investigations revealed at least one virus and no bacterium; mixed , if microbiological investigations revealed at least one virus and one bacterium; and no etiology, if microbiological investigations revealed no virus and no bacterium.", "Title: Inferring R(0) in emerging epidemics\u2014the effect of common population structure is small\nPassage: by . We calculate estimates of R 0 using these two estimators for 250 simulation runs. As predicted by the theory, the simulation results show that for each run the estimates are close to the actual value without a systematic bias . Note that in figure 4 we compare two estimators of R 0 , which are each based on a finite number of observations and hence not exact. We do not compare the estimates of R 0 with the computed value of R 0 based on the model parameters. Title: Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data", "Passage: process. In other words, the likelihood function for estimating R 0 is: where T is the most recent time point of observation within an early epidemic growth stage. The maximum likelihood estimate of R 0 is obtained by minimizing the negative logarithm of , and the 95% CI are derived from the profile likelihood. Table 1 shows the estimates of r and R 0 for HIV in France, Western Germany and the UK. The maximum likelihood estimates of r ranged from 1.15 to 2.15 per year with the smallest estimate in France and the highest in Western Germany. The 95% Title: Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data", "Passage: epidemic in a randomly-mixing population is given by 1-1/R 0 . In addition, R 0 gives an estimate of the so-called final size, i.e., the proportion of the population that will experience infection by the end of an epidemic . Title: Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data\nPassage: The purpose of the present study is to offer an improved framework for estimating R 0 from early epidemic growth data, which may be slightly more tractable among non-experts as compared with the above mentioned estimator . A likelihood-based approach is proposed to permit derivation of the uncertainty bounds of R 0 . For an exposition of the proposed method, the incidence data of the HIV epidemic in Europe is explored.", "Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\nPassage: Beyond a robust assessment of overall severity, it is also important to determine high risk groups. Infections would likely be more severe in older adults, obese individuals or those with underlying medical conditions, but there have not yet been reports of severity of infections in pregnant women, and very few cases have been reported in children . Title: SARS to novel coronavirus \u2013 old lessons and new lessons\nPassage: Given the likely impact on at least the Chinese economy and probably the global economy, it will be important to understand the role and the effectiveness of public health measures on this scale for the future. Title: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak", "Passage: Those under 18 years are a critical group to study in order to tease out the relative roles of susceptibility vs severity as possible underlying causes for the very rare recorded instances of infection in this age group. Are children protected from infection or do they not fall ill after infection? If they are naturally immune, which is unlikely, we should understand why; otherwise, even if they do not show symptoms, it is important to know if they shed the virus. Obviously, the question about virus shedding of those being infected but asymptomatic leads to the crucial question of infectivity. Title: On pandemics and the duty to care: whose duty? who cares?", "Passage: In 2003, the world witnessed the spread of a novel and deadly virus, namely SARS CoV. The health care workers and hospital systems that bore the brunt of the SARS outbreak continue to struggle with the aftermath of the crisis. Indeed, HCWs -both in clinical care and in public health -were severely tested by SARS. Unprecedented demands were placed on their skills and expertise, and their personal commitment to their profession was severely tried. Many were exposed to serious risk of morbidity and mortality; indeed, approximately 30% of reported cases were among HCWs, some of whom died from the infection", "Title: Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China\nPassage: The median time from onset of illness to first medical care was 1 day . Time from onset to hospitalization was 4 days , and time from onset to confirmation was 7 days . Here, 24 cases received oseltamivir treatment after a median of 5 days from the onset of symptoms, with 5 patients receiving oseltamivir treatment within 48 h of onset. The 14 patients who died did so at a median of 10 days after onset. According to the Mann-Whitney test, there was no significant difference between the fatal and nonfatal groups with respect to time elapsed from onset Title: A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections", "Passage: 'Time from symptom onset' was defined as the duration from the appearance of the first presenting symptom till the time of blood sample collection. The distribution of 'time from symptom onset' in our cohort peaked at 2-4 days after the initiation of symptoms with substantial proportions of patients turning to medical assistance either sooner or later . Figure S7 . Distribution of time from initiation of symptoms . N/A -healthy controls or patients for which data was not obtained. Title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020", "Passage: person rather than because of severe disease. The time from onset of symptoms to hospitalisation ranged between 0 and 10 days with a mean of 3.7 days . The mean number of days to hospitalisation was 2.5 days for cases imported from China, but 4.6 days for those infected in Europe. This was mostly a result of delays in identifying the index cases of the two clusters in France and Germany. In the German cluster, for example, the first three cases detected locally were hospitalised in a mean of 5.7 days, whereas the following six took only a mean of Title: Clinical factors associated with severity in hospitalized children infected with avian influenza (H5N1)", "Passage: in the WHO report and 69.4% in our pooled data. The median time from onset of symptoms to admission was 4 days among all of the patients reported in our five studies and 5 days in patients reported to have died in the WHO report. The median time from onset to admission was 6 days in the pooled data. Cases were mainly identified through passive surveillance in the WHO report, whereas we also included cases collected through hospital medical records in our study. Thus, the CFR in the pooled data was higher than that of the WHO report, and the", "Title: Functional Analysis of the 5\u2032 Genomic Sequence of a Bovine Norovirus\nPassage: protein from the ORF1 polyprotein. Title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan\nPassage: A novel short putative protein with 4 helices and no homology to existing SARS-CoV or SARS-r-CoV protein was found within Orf3b . It is notable that SARS-CoV deletion mutants lacking orf3b replicate to levels similar to those of wildtype virus in several cell types , suggesting that orf3b is dispensable for viral replication in vitro. But orf3b may have a role in viral pathogenicity as Vero E6 but not 293T cells transfected with a construct expressing Orf3b underwent necrosis as early as 6 h after transfection and underwent simultaneous necrosis and apoptosis at later time points . Orf3b was also Title: Functional Analysis of the 5\u2032 Genomic Sequence of a Bovine Norovirus", "Passage: As it was clear that the JV 59GS did not posses any IRES-like functions it was necessary to determine the location of translation initiation within ORF1. This was predicted be the ATG encoding methionine at nucleotide position 22, as it is situated in a favourable context for translation initiation . To investigate this multiple translation termination codons were inserted into the JV genome within the 3B-encoding region, downstream of the 59GS, to halt translation at a defined point. In vitro transcription and translation of this construct would, in theory, yield a product whose size would relate to the initiation codon Title: First Complete Genome Sequence of a French Bovine coronavirus Strain", "Passage: M, and N genes of the obtained BCoV were submitted to a Blastn analysis. According to these analyses, the orf1ab gene is closely related to the Dromedary camel coronavirus HKU23-23-362F strain from the United Arab Emirates , with a nucleotide identity of 99.19%. Conversely, the NS2, HE, S, ns5, and M genes are closely related to the BCoV Bubalus/Italy/179/07-11 strain , with nucleotide identities of 99.88%, 99.45%, 99.02%, 98.79%, and 99.28%, respectively. The E gene is closely related to the Chinese Bovine coronavirus strain BCV-AKS-01 , with a nucleotide identity of 100%. Finally, the highest Blastn score for the N", "Title: Sera from severe trauma patients with pneumonia and without infectious complications have differential effects on neutrophil biology\nPassage: their number as well as their viability was determined by the trypan blue exclusion assay. For the analysis of the effects of sera obtained from TP, PMN were cultured in media containing 20% of TP serum. Only cell cultures with a purity of >95% were utilized for experimental use. Title: Sera from severe trauma patients with pneumonia and without infectious complications have differential effects on neutrophil biology", "Passage: these results suggest that the ratio of CD11b to CD62L and especially increased CD62L expression may reflect the enhanced migratory capacity of neutrophils. Interestingly, ROS production was not markedly altered in general, while it was strongly reduced by applying sera from patients without infectious complications to isolated neutrophils compared to its increase by using sera from patients who developed pneumonia. This data indicate at the high relevance of studying neutrophil function after trauma and their already immediately after trauma modified activity depending on the post-injury clinical course of patients that may have predictive or even therapeutic potential. Title: Sera from severe trauma patients with pneumonia and without infectious complications have differential effects on neutrophil biology", "Passage: a compensatory anti-inflammatory response syndrome resulting in a mixed antagonist response syndrome . Title: Sera from severe trauma patients with pneumonia and without infectious complications have differential effects on neutrophil biology\nPassage: Blood samples from healthy volunteers were withdrawn in heparinized tubes and kept at room temperature until isolation of neutrophil granulocytes. The blood samples taken from HV were obtained between 7 and 11 a.m.", "Title: Virus-Vectored Influenza Virus Vaccines\nPassage: although cellular immune responses appeared to contribute to protection, serum antibody was sufficient for protection from challenge . Intramuscular immunization with PIV5-H5 was also shown to be effective at inducing neutralizing antibody responses and protecting against lethal influenza virus challenge . PIV5 expressing the NP protein of HPAIV was also efficacious in the murine immunization and challenge model, where a single intranasal immunization induced robust CD8 + T cell responses and protected against homologous and heterosubtypic virus challenge . Title: Virus-Vectored Influenza Virus Vaccines", "Passage: cells and replicated similarly to the wild type virus, and importantly, was not pathogenic in immunodeficient mice . Additionally, a single intranasal immunization in a murine model of influenza infection was shown to induce neutralizing antibody responses and protect against a virus expressing homologous HA protein . PIV5 has also been explored as a vaccine against HPAIV. Recombinant PIV5 vaccines expressing the HA or NP from VN1203 were tested for efficacy in a murine challenge model. Mice intranasally vaccinated with a single dose of PIV5-H5 vaccine had robust serum and mucosal antibody responses, and were protected from lethal challenge. Notably, Title: Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines", "Passage: group received 10 7 pfu of MVA prime-boost, subcutaneously. Serum samples obtained 3 weeks after priming and 3 weeks after boosting were tested for H5-specific IgG . Error bars represent standard deviation. Mice were subsequently challenged with 10 6 pfu of influenza rgA/Viet Nam/1203/2004, and weighed daily for two weeks . A \"+\" sign represents a mouse that succumbed to infection. Title: Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret\nPassage: Viral challenge experiments were performed 3 weeks after the last immunization. All challenged animals were exposed under CO 2 anesthesia to an intranasal viral inoculum of 100 LD 50 of A/ Vietnam/1203/2004 virus. Body weight and survival were monitored for 21 days. The viral challenge experiments were conducted at the Centers for Disease Control and Prevention as previously described ."]