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Title:
Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts
Abstract:
Summary Background Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19).
Whether this strategy will achieve control depends on characteristics of both the pathogen and the response.
Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.
Methods We developed a stochastic transmission model, parameterised to the COVID-19 outbreak.
We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen.
We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections.
We assumed isolation prevented all further transmission in the model.
Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total.
We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.
Findings Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset.
Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced.
To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced.
The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5.
For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.
Interpretation In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months.
The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms.
This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.
Funding Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK. | 211,832,114 |
Title:
Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation
Abstract:
Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation.
A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease.
Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation.
Using comparative genomics and surface plasmon resonance, we identified parasite-derived peptides that have the sequence-specific ability to increase E2F signaling by binding E2F negative regulator Retinoblastoma-1 (RB).
Using these peptides as a tool to probe host E2F signaling, we show that the disruption of RB complexes ex vivo leads to activation of E2F-driven transcription and increased leukocyte proliferation in an infection-dependent manner.
This result is consistent with existing models and, together, they support a critical role of E2F signaling for Theileria-induced host cell proliferation, and its potential direct manipulation by one or more parasite proteins. | 211,836,457 |
Title:
Advanced diffusion magnetic resonance imaging in patients with Alzheimer's and Parkinson's diseases
Abstract:
The prevalence of neurodegenerative diseases is increasing as human longevity increases.
The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated.
It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques.
Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues.
Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings; however, it has several limitations.
To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases.
This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively. | 212,114,428 |
Title:
New Weevils (Coleoptera, Curculionoidea) from the Earlymost Eocene Oise Amber
Abstract:
Several new tribes, genera and species of Curculionoidea are described from the earlymost Eocene Oise amber (France), viz., the new tribes Oiserhinini trib.
nov. (type genus: Oiserhinus gen. nov.) (in Anthribidae: Anthribinae), Palaeotanaini trib.
nov. (type genus: Palaeotanaos Kirejtshuk, Legalov et Nel, 2015) (in Brentidae: Apioninae), Sciabregmini trib.
nov. (type genus: Sciabregma Scudder 1893) (in Curculionidae: Molytinae); the new genera Oiserhinus gen. nov. (type species: Oiserhinusinsolitus sp. nov.), Oisecalles gen. nov. (type species: Oisecalles latosquamosus sp. nov.) in Cryptorhynchini: Cryptorhynchina), Rhinoporkus gen. nov. (type species: Rhinoporkus gratiosus sp. nov.) (in Dryophthorinae: Dryophthorini), Jantarhinus gen. nov. (type species: Jantarhinus compressus sp. nov.) (in Conoderinae: Conoderini), Jantaronosik gen. nov. (type species: Jantaronosik nebulosus sp. nov.) (in Curculioninae: Acalyptini), Tolstonosik gen. nov. (type species: Tolstonosikoisensis sp. nov.) (in Entiminae: Eudiagogini); and the new species Oiserhinusinsolitus sp. nov., Sciabregmasquamosa sp. nov., Oisecalles latosquamosus sp. nov., Rhinoporkus gratiosus sp. nov., Jantarhinus compressus sp. nov., Jantaronosik nebulosus sp. nov., and Tolstonosikoisensis sp. nov. The generic name Protoceletes Rheinheimer, 2007, syn.
nov. is synonymized under Electrotribus Hustache, 1942.
New combination of name (Electrotribuswolfschwenningerae (Rheinheimer, 2007), comb.
nov. is established.
Synopsis of the weevil findings from described groups are presented. | 212,407,787 |
Title:
Formulating an Ethics of Pharmaceutical Disinvestment
Abstract:
There is growing interest among pharmaceutical policymakers in how to "disinvest" from subsidized medicines.
This is due to both the rapidly rising costs of healthcare and the increasing use of accelerated and conditional reimbursement pathways which mean that medicines are being subsidized on the basis of less robust evidence of safety and efficacy.
It is crucial that disinvestment decisions are morally sound and socially legitimate, but there is currently no framework to facilitate this.
We therefore reviewed the bioethics literature in order to identify ethical principles and concepts that might be relevant to pharmaceutical disinvestment decisions.
This revealed a number of key ethical considerations-both procedural and substantive-that need to be considered when making pharmaceutical disinvestment decisions.
These principles do not, however, provide practical guidance so we present a framework outlining how they might be applied to different types of disinvestment decisions.
We also argue that, in this context, even the most rigorous ethical reasoning is likely to be overridden by moral intuitions and psychological biases and that disinvestment decisions will need to strike the right balance between respecting justifiable moral intuitions and overriding unjustifiable psychological impulses. | 212,408,217 |
Title:
Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient
Abstract:
Coronaviruses have been implicated in nosocomial outbreaks with environmental contamination as a route of transmission.
Similarly, nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported.
However, the mode of transmission and extent of environmental contamination are unknown. | 212,408,365 |
Title:
Impact of Illness on Electronic Health Use (The Seventh Tromsø Study - Part 2): Population-Based Questionnaire Study
Abstract:
BACKGROUND ::: Patients who suffer from different diseases may use different electronic health (eHealth) resources.
Thus, those who plan eHealth interventions should take into account which eHealth resources are used most frequently by patients that suffer from different diseases. ::: ::: ::: OBJECTIVE ::: The aim of this study was to understand the associations between different groups of chronic diseases and the use of different eHealth resources. ::: ::: ::: METHODS ::: Data from the seventh survey of the Tromsø Study (Tromsø 7) were analyzed to determine how different diseases influence the use of different eHealth resources.
Specifically, the eHealth resources considered were use of apps, search engines, video services, and social media.
The analysis contained data from 21,083 participants in the age group older than 40 years.
A total of 15,585 (15,585/21,083; 73.92%) participants reported to have suffered some disease, 10,604 (10,604/21,083; 50.29%) participants reported to have used some kind of eHealth resource in the last year, and 7854 (7854/21,083; 37.25%) participants reported to have used some kind of eHealth resource in the last year and suffered (or had suffered) from some kind of specified disease.
Logistic regression was used to determine which diseases significantly predicted the use of each eHealth resource. ::: ::: ::: RESULTS ::: The use of apps was increased among those individuals that (had) suffered from psychological problems (odds ratio [OR] 1.39, 95% CI 1.23-1.56) and cardiovascular diseases (OR 1.12, 95% CI 1.01-1.24) and those part-time workers that (had) suffered from any of the diseases classified as others (OR 2.08, 95% CI 1.35-3.32).
The use of search engines for accessing health information increased among individuals who suffered from psychological problems (OR 1.39, 95% CI 1.25-1.55), cancer (OR 1.26, 95% CI 1.11-1.44), or any of the diseases classified as other diseases (OR 1.27, 95% CI 1.13-1.42).
Regarding video services, their use for accessing health information was more likely when the participant was a man (OR 1.31, 95% CI 1.13-1.53), (had) suffered from psychological problems (OR 1.70, 95% CI 1.43-2.01), or (had) suffered from other diseases (OR 1.43, 95% CI 1.20-1.71).
The factors associated with an increase in the use of social media for accessing health information were as follows: (had) suffered from psychological problems (OR 1.65, 95% CI 1.42-1.91), working part time (OR 1.35, 95% CI 0.62-2.63), receiving disability benefits (OR 1.42, 95% CI 1.14-1.76), having received an upper secondary school education (OR 1.20, 95% CI 1.03-1.38), being a man with a high household income (OR 1.67, 95% CI 1.07-2.60), suffering from cardiovascular diseases and having a high household income (OR 3.39, 95% CI 1.62-8.16), and suffering from respiratory diseases while being retired (OR 1.95, 95% CI 1.28-2.97). ::: ::: ::: CONCLUSIONS ::: Our findings show that different diseases are currently associated with the use of different eHealth resources.
This knowledge is useful for those who plan eHealth interventions as they can take into account which type of eHealth resource may be used for gaining the attention of the different user groups. | 212,418,978 |
Title:
Life-Changing Injuries: Psychological Intervention Throughout the Recovery Process Following Traumatic Amputations
Abstract:
Trauma amputation triggers intense psychological reactions and causes monumental life changes.
Roughly half of amputations are the result of medical complications and half are from traumatic events such as industry and automobile accidents.
Shock, dismay, and anger are typical initial emotional reactions.
Pain, depression, and adaptation of life changes are longer term challenges.
Psychological care should be an integrated component during all stages of recovery and adjustment. | 212,420,687 |
Title:
Innervated and vascularized radial thenar flap free grafting for partial penile reconstruction after traumatic penile amputation: a case report and surgical techniques
Abstract:
Penile amputation is a rare deformity mostly resulting from self-mutilation, felonious assault, or accidental trauma, and penile reconstruction or phalloplasty is necessary when microreplantation cannot be performed.
Here we report a rare case of a 42-year-old man with traumatic penile amputation and describe surgical techniques for partial penile reconstruction by using a novel innervated and vascularized radial thenar flap free grafting method.
Excellent cosmetic and functional results were reported with no severe complications of dysuria, urethral stricture, and urinary fistula were observed during the 23 months of postoperative follow-up time.
It is believed that innervated and vascularized radial thenar flap free grafting is an acceptable treatment option for patients with traumatic penile amputation. | 212,425,385 |
Title:
Recurrent Stroke In 34 Year-Old, Unusual Presentation of Non-Bacterial Endocarditis
Abstract:
Factor V Leiden (FVL) and prothrombin G20210A (PGM) mutations are the most frequent genetic risk factors involved in deep venous thrombosis in Caucasians.
Being heterozygous for both seems to increase the risk of venous events but it is not well established if the association increases the risk of arterial thrombosis or other thrombotic events.
We present a case of recurrent stroke caused by non-bacterial thrombotic endocarditis (NBTE) in a 34-year-old Caucasian man heterozygous for both FVL and PGM.
His diagnosis of NBTE was confirmed with pathology in the absence of other causes of NBTE. | 212,429,812 |
Title:
Life Cycle and Fertility Life Table of Zelus vespiformis (Hemiptera: Reduviidae)
Abstract:
Zelus vespiformis Hart (Hemiptera: Reduviidae) is a native predator which has been recorded frequently predating on some insects pest of coffee plantations in Colombia.
In order to know its biological parameters, its life cycle and fertility life table were evaluated under laboratory conditions at Cenicafe, using Galleria mellonella Linnaeus (Lepidoptera: Pyralidae).
To obtain the duration and survival of immature stages, 716 eggs were followed and 23 adults pairs (♂: ♀) were established to construct the life table.
The mean duration from egg to adult was 112.65±0.76 days; the egg incubation period was 23.22±0.21 days; and nymphs had 11.75% survival to the adult stage.
The longevity of adults was 25.86±2.94 and 30.39±2.26 days for females and males respectively.
The mean number of eggs per female was 105.55±10.75.
The parameters of the fertility life table were net reproductive rate R0=5.19 (2.54–10.28); generation time T=106.75 (101.7–114.0) days, intrinsic growth rate rm=0.015 (0.009–0.022), and finite growth rate λ=1.015 (1.009–1.023).
This information forms a biological basis for initiating studies that pretend to determine the potential of this insect as predator. | 212,430,755 |
Title:
Evaluation of extracts of Caryocar brasiliense (Caryocaraceae) for theirinsecticidal potential on Lutzomyia longipalpis (Diptera, Psychodidae), themain vector of visceral leishmaniasis in brazil.
Abstract:
In Brazil, kala-azar or Visceral Leishmaniasis (VL) is a parasitic disease with a high degree of lethality, transmitted to humans mainly by sandflies belonging to the species Lutzomyia longipalpis.
The search for alternative products for the elimination of this vector aims to minimize the impacts caused by the synthetic insecticides used by the control programs.
Therefore, the insecticidal activity of Caryocar brasiliense plant extracts on Lutzomyia longipalpis was evaluated in this study.
Methods: Hydroethanolic and cyclohexane extracts of leaves and bark were obtained at concentrations of 50, 100, 200 and 400 mg/mL. Thirty sand flies were exposed to the.... Read More | 212,432,211 |
Title:
The role of preoperative 3D-ultrasound in intraoperative judgement for hysteroscopic adhesiolysis
Abstract:
Background ::: Hysteroscopic adhesiolysis (HA) remains the mainstay of treatment for intrauterine adhesions (IUA).
In cases of moderate or severe IUA, the assistance of various adjunctive aids are usually sought to improve HA's success rate.
Among these, intraoperative transabdominal ultrasound (TAS) is the most common; however, it has certain limitations.
Preoperative three-dimensional transvaginal ultrasound (3D-TVUS) has been accepted as a non-invasive way to provide accurate information about the uterine cavity.
This prospective, non-randomized controlled study will assess the effects of pre-operative 3D-TVUS prior to HA in improving the surgeon's intraoperative judgement. ::: ::: ::: Methods ::: A total of 362 patients, who met the inclusion criteria, aged between 18 and 45 years and diagnosed with moderate or severe IUA underwent HA at our hospital from March 2018 to December 2018.
Participants were divided into 2 groups; the study group; n=182 performed 3D-TVUS evaluation prior to HA, and the control group; n=180 underwent HA without preoperative 3D-TVUS evaluation.
The following basic information were collected prospectively for both groups: age, parity, history of abortion, degree of IUA, surgical complications and number of hysteroscopic interventions.
The data obtained from 3D-TVUS in the study group was carefully studied at the preoperative stage by the operator and was integrated into intraoperative findings, further assisting with intraoperative decisions.
The guiding value of preoperative 3D-TVUS for HA was evaluated by comparing and analyzing the postoperative exposure rate of clearly visible tubal ostia between the groups. ::: ::: ::: Results ::: Based on the basic information (P>0.05) collected preoperatively, there were no statistically significant differences between the groups.
Postoperatively, the study group had a better surgical success rate with a more significant AFS score reduction (4.71±2.05; P<0.0001) and better morphological restoration of the uterine cavity, with more adhesion-free uterine horns and more clearly visible fallopian tube ostia (P<0.0001) following HA. ::: ::: ::: Conclusions ::: This study showed that preoperative 3D-TVUS evaluation helped the hysteroscopists with their intraoperative decision-making while carrying out HA.
In comparison to those who did not perform preoperative 3D ultrasound, those who underwent 3D-TVUS evaluation had a better surgical success rate in retrieving the fallopian tube ostia and the restoration of normal uterine cavity morphology. | 212,446,855 |
Title:
Study on the release and sensory perception of encapsulated d‐limonene flavor in crystal rock candy using the time–intensity analysis and HS‐GC/MS spectrometry
Abstract:
This research was conducted to evaluate encapsulated d-limonene perception and release in rock candy.
Microcapsules with wall materials of 75/25 of gum Arabic/Maltodextrin by 20% of wall materials) were produced for using in rock candy.
To evaluate the flavor release from rock candy by time-intensity method, a model system was developed and time-intensity sensory evaluation was conducted by trained sensory panelists in order to determine the effect of three different matrices (water, water and flavored rock candy, and water with flavored rock candy and citric acid (pH = 3) at three serving temperatures (10, 45, and 75°C) on the perception of d-limonene release.
Results showed that release of d-limonene from flavored rock candy with acid citric (pH = 3) at 75°C had the highest perceived sensation whereas the matrix of microcapsule in water at 10°C had the lowest perception.
On the other hand, increasing the temperature from 10 to 75°C had significant effects on the release and perception of d-limonene (p < .05).
Headspace gas chromatography-mass spectrophotometry confirmed results from time-intensity sensory evaluation, which indicated that the release of d-limonene increased in the presence of sucrose and citric acid (pH = 3). | 212,550,674 |
Title:
Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity
Abstract:
CD4+ memory T cells play an important role in protective immunity and are a key target in vaccine development.
Many studies have focused on T central memory (Tcm) cells, whereas the existence and functional significance of long-lived T follicular helper (Tfh) cells are controversial.
Here, we show that Tfh cells are highly susceptible to NAD-induced cell death (NICD) during isolation from tissues, leading to their underrepresentation in prior studies.
NICD blockade reveals the persistence of abundant Tfh cells with high expression of hallmark Tfh markers to at least 400 days after infection, by which time Tcm cells are no longer found.
Using single-cell RNA-seq, we demonstrate that long-lived Tfh cells are transcriptionally distinct from Tcm cells, maintain stemness and self-renewal gene expression, and, in contrast to Tcm cells, are multipotent after recall.
At the protein level, we show that folate receptor 4 (FR4) robustly discriminates long-lived Tfh cells from Tcm cells.
Unexpectedly, long-lived Tfh cells concurrently express a distinct glycolytic signature similar to trained immune cells, including elevated expression of mTOR-, HIF-1-, and cAMP-regulated genes.
Late disruption of glycolysis/ICOS signaling leads to Tfh cell depletion concomitant with decreased splenic plasma cells and circulating antibody titers, demonstrating both unique homeostatic regulation of Tfh and their sustained function during the memory phase of the immune response.
These results highlight the metabolic heterogeneity underlying distinct long-lived T cell subsets and establish Tfh cells as an attractive target for the induction of durable adaptive immunity. | 212,560,552 |
Title:
The clinicopathological study of lung cancer concealed in end-stage of interstitial lung disease
Abstract:
Background: Most of the patients with interstitial lung disease (ILD) complicated with lung cancer (ILD- LC) showed non-specific clinical manifestations.
This study is to explore the incidence of lung cancer concealed in the end-stage of interstitial lung disease (LC-CES-ILD). ::: Methods: A total of 154 cases of lung transplantation from March 2017 to December 2018 were studied retrospectively, of which 7 cases were found to be LC-CES-ILD.
Serum tumor biomarkers were examined.
HE and immunohistochemical staining were performed for the tumor tissue after the operation.
Lung cancer (LC) drive gene was detected by quantitative real-time polymerase chain reaction (qRT-PCR).
Results: The percentage of male patients with idiopathic pulmonary fibrosis (IPF) was 44.81%.
The expression of all tumor biomarkers was significantly increased in 6 patients with LC-CES-ILD.
After operation, apparent destruction of lung tissue structure was observed in 7 patients, and honeycomb appearance could be seen in some areas.
After HE staining, 4 cases of acinar type and 2 cases of mucinous adenocarcinoma were found.
The results of molecular pathology showed that only one case of mucinous adenocarcinoma had KRAS mutation, and no mutation of LC co-driving gene was found in the rest of the cases.
::: Conclusions: It is necessary to detect the lung tissue of patients with end-stage ILD, which were probably correlated with the occurrence of LC concealed, before lung transplantation. | 212,597,569 |
Title:
The Price equation and reproductive value
Abstract:
The Price equation is widely recognized as capturing conceptually important properties of natural selection, and is often used to derive versions of Fisher’s fundamental theorem of natural selection, the secondary theorems of natural selection and other significant results.
However, class structure is not usually incorporated into these arguments.
From the starting point of Fisher’s original connection between fitness and reproductive value, a principled way of incorporating reproductive value and structured populations into the Price equation is explained, with its implications for precise meanings of (two distinct kinds of) reproductive value and of fitness.
Once the Price equation applies to structured populations, then the other equations follow.
The fundamental theorem itself has a special place among these equations, not only because it always incorporated class structure (and its method is followed for general class structures), but also because that is the result that justifies the important idea that these equations identify the effect of natural selection.
The precise definitions of reproductive value and fitness have striking and unexpected features.
However, a theoretical challenge emerges from the articulation of Fisher’s structure: is it possible to retain the ecological properties of fitness as well as its evolutionary out-of-equilibrium properties?
This article is part of the theme issue ‘Fifty years of the Price equation’. | 212,628,786 |
Title:
Direct SERDS sensing of molecular biomarkers in plants under field conditions
Abstract:
Molecular biomarkers such as microRNAs (miRNAs) play important roles in regulating various developmental processes in plants.
Understanding these pathways will help bioengineer designing organisms for efficient biomass accumulation.
Current methods for RNA analysis require sample extraction and multi-step sample analysis, hindering work in field studies.
Recent work in the incorporation of nanomaterials for plant bioengineering research is leading the way of an agri-tech revolution.
As an example, surface-enhanced Raman scattering (SERS)-based sensors can be used to monitor RNA in vivo.
However, the use of SERS in the field has been limited due to issues with observing Raman signal over complex background.
To this end, shifted-excitation Raman difference spectroscopy (SERDS) offers an effective solution to extract the SERS signal from high background based on a physical approach.
In this manuscript, we report the first application of SERDS on SERS sensors.
We investigated this technique on SERS sensor developed for the detection of a microRNA biomarker, miR858.
We tested the technique on in vitro samples and validated the technique by detecting the presence of exogenous miR858 in plants directly under ambient light in a growth chamber.
The possibility of moving the detection of nucleic acid targets outside the constraints of laboratory setting enables numerous important bioengineering applications.
Such applications can revolutionize biofuel production and agri-tech through the use of nanotechnology-based monitoring of plant growth, plant health, and exposure to pollution and pathogens. | 212,630,028 |
Title:
Correlating the three-dimensional atomic defects and electronic properties of two-dimensional transition metal dichalcogenides
Abstract:
The electronic, optical and chemical properties of two-dimensional transition metal dichalcogenides strongly depend on their three-dimensional atomic structure and crystal defects.
Using Re-doped MoS2 as a model system, here we present scanning atomic electron tomography as a method to determine three-dimensional atomic positions as well as positions of crystal defects such as dopants, vacancies and ripples with a precision down to 4 pm.
We measure the three-dimensional bond distortion and local strain tensor induced by single dopants.
By directly providing these experimental three-dimensional atomic coordinates to density functional theory, we obtain more accurate electronic band structures than derived from conventional density functional theory calculations that relies on relaxed three-dimensional atomic coordinates.
We anticipate that scanning atomic electron tomography not only will be generally applicable to determine the three-dimensional atomic coordinates of two-dimensional materials, but also will enable ab initio calculations to better predict the physical, chemical and electronic properties of these materials. | 212,642,445 |
Title:
On a knife’s edge of a COVID-19 pandemic: is containment still possible?
Abstract:
In 2018, we undertook a training simulation of a pandemic in Sydney, underpinned by mathematical modelling, which went through precisely the issues we are dealing with now in trying to contain the spread of coronavirus disease 2019 (COVID-19) – namely mass quarantine, travel restrictions, stricken cruise ships, mass surveillance, finding enough beds for case isolation and mass contact tracing.
Governments everywhere plan for pandemics, because their impact can cause sharp shocks to economies and societies and require a substantial surge in health system capacity.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, probably emerged in late 2019, and began infecting humans in December 2019.
Only half of the initial cluster of cases had exposure at the Huanan Seafood Wholesale Market in Wuhan.
By mid-January it was clear there was substantial person-to-person transmission.
Like SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), severe infection and mortality is more common in older adults.
Estimates of the reproduction number (R0), or the number of susceptible people, on average, that an infectious person will infect, have varied between 2 and 7.
The best estimate of R0 is 2.2, based on date of illness onset.
This compares with an R0 of 1.83 for Ebola virus disease, 1.54 for influenza A and 2.9 for SARS.7 Most estimates have been based on date of reported cases, not date of symptom onset.
The reporting date can result in bias, as illustrated in World Health Organization (WHO) situation reports which show the difference between epidemic curves plotted with symptom onset versus reporting date.
Outbreaks have also occurred in closed settings such as cruise ships, prisons, hospitals and aged care facilities, with growing epidemics in other countries.
When sustained transmission was largely localised to China, containment was a feasible goal.
However, in Iran and Italy, a high ratio of deaths to cases suggests a substantial proportion of undiagnosed cases and sustained community transmission between people without travel as a risk factor, leading experts to believe a pandemic is likely. | 212,651,812 |
Title:
A Single “All-in-One” Helper-Dependent Adenovirus to Deliver Donor DNA and CRISPR/Cas9 for Efficient Homology-Directed Repair
Abstract:
Abstract In this study we developed a single helper-dependent adenovirus to deliver all of the components (donor DNA, Cas9 and gRNA) needed to achieve high efficiency gene targeting and homology-directed repair in transduced cells.
We show that these “all-in-one” HDAds are up to 117-fold more efficient at gene targeting than donor HDAds that do not express CRISPR/Cas9 in human iPSCs.
The vast majority (>90%) of targeted recombinants had only one allele targeted and this was accompanied by high frequency indel formation in the non-targeted allele at the site of Cas9 cleavage.
These indels varied in size and nature and included large deletions of ∼8 kb.
The remaining minority of recombinants had both alleles targeted (so-called bi-allelic targeting).
These all-in-one HDAds represent an important platform for accomplishing and expanding the utility of homology-directed repair, especially for difficult-to-transfect cells and for in vivo applications. | 212,652,443 |
Title:
Getting R-AEDI to save lives in Singapore
Abstract:
Early cardiopulmonary resuscitation (CPR) and defibrillation prior to the arrival of emergency medical services can improve survival from out-of-hospital cardiac arrest (OHCA) with good neurological outcome.
However, the rate of local bystander CPR is only 24.3% and bystander defibrillation 2.1%.
In 2015, the R-AEDI (Registry for AED Integration) initiative was started to improve OHCA survival rates.
R-AEDI alerts volunteers to nearby OHCA cases via the myResponder mobile application.
In 2015-2017, 7,682 AEDs were mapped and made accessible via this app.
Comprehensive site inspections also resulted in fewer non-functional AEDs, as AED owners were educated on the importance of the maintenance of pads and batteries.
The AED heat map allows us to identify areas that are lacking in or require improved public access AED coverage.
The online AED registry found in the myResponder app is useful to locate AEDs rapidly during OHCAs.
More community education would improve the rate of bystander defibrillation. | 212,652,506 |
Title:
Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms
Abstract:
Purpose ::: Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs).
To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha-L-iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS). ::: ::: ::: Methods ::: We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan.
The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early-onset MPSI (Hurler's syndrome).
Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool. ::: ::: ::: Results ::: Every case of early-onset MPSI was predicted correctly by the tool.
No normal newborn was incorrectly identified as having early-onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol.
The PPV was estimated to be 99.9%. ::: ::: ::: Conclusions ::: Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment.
This bivariate analysis-based approach, which was developed for Krabbe disease, can be extended to additional screened disorders. | 212,652,631 |
Title:
Intrathyroidal ectopic thymus in 8-year-old girl: a case report
Abstract:
We provide a case report of two thyroid nodules in an 8-year-old girl, which revealed malignant ultrasonographic findings and which were confirmed as ectopic thymic tissue by total thyroidectomy.
The ultrasound presentations of intrathyroidal thymus glands were similar to those of the malignant thyroid nodules.
In addition, in this case, there were two ectopic thymus lesions in the thyroid gland, which undoubtedly increased the difficulty of diagnosis.
The occurrence of multiple ectopic thymic lesions in the thyroid gland was different from previous reports.
Therefore, clinicians should take into consideration this rare entity, and should not mistake it as a thyroid neoplasm; moreover, they should not perform extensive thyroid resection. | 212,653,124 |
Title:
Understanding Individual and Family Experiences Associated with DUP: Lessons from the Early Assessment and Support Alliance (EASA) Program in Oregon, USA
Abstract:
Research shows that a longer duration of untreated psychosis (DUP) is associated with worse psychiatric outcomes, with average length of DUP of 73 weeks in the U.S. The aim was to examine the DUP period for first episode psychosis in Oregon, with a focus on the processes between the first positive symptoms and first treatment.
To investigate DUP, researchers used methods consistent with grounded theory to collect data from 9 participants and their families about the process between onset of psychotic symptoms and entrance into treatment.
Results suggest that recognition of symptoms was the primary driver of help-seeking in this study, and this was influenced by type of symptom as well as the presence or absence of supportive others, which in most cases was regular family contact.
Implications indicate a need for in-depth research on individual and family recognition of symptoms, as well as underscoring the need for community education. | 212,654,331 |
Title:
A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicase nsP13 in the unwinding of duplex RNA
Abstract:
Severe acute respiratory syndrome coronavirus nonstructural protein 13 (SCV nsP13), a superfamily 1 helicase, plays a central role in viral RNA replication through the unwinding of duplex RNA and DNA with a 5' single-stranded tail in a 5' to 3' direction.
Despite its putative role in viral RNA replication, nsP13 readily unwinds duplex DNA by cooperative translocation.
Herein, nsP13 exhibited different characteristics in duplex RNA unwinding than that in duplex DNA.
nsP13 showed very poor processivity on duplex RNA compared with that on duplex DNA.
More importantly, nsP13 inefficiently unwinds duplex RNA by increasing the 5'-ss tail length.
As the concentration of nsP13 increased, the amount of unwound duplex DNA increased and that of unwound duplex RNA decreased.
The accumulation of duplex RNA/nsP13 complexes increased as the concentration of nsP13 increased.
An increased ATP concentration in the unwinding of duplex RNA relieved the decrease in duplex RNA unwinding.
Thus, nsP13 has a strong affinity for duplex RNA as a substrate for the unwinding reaction, which requires increased ATPs to processively unwind duplex RNA.
Our results suggest that duplex RNA is a preferred substrate for the helicase activity of nsP13 than duplex DNA at high ATP concentrations. | 212,654,333 |
Title:
Immune-based therapies for hepatocellular carcinoma
Abstract:
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death.
The immune-rich contexture of the HCC microenvironment makes this tumour an appealing target for immune-based therapies.
Here, we discuss how the functional characteristics of the liver microenvironment can potentially be harnessed for the treatment of HCC.
We will review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area. | 212,654,391 |
Title:
Individual, but not population asymmetries, are modulated by social environment and genotype in Drosophila melanogaster
Abstract:
Theory predicts that social interactions can induce an alignment of behavioral asymmetries between individuals (i.e., population-level lateralization), but evidence for this effect is mixed.
To understand how interaction with other individuals affects behavioral asymmetries, we systematically manipulated the social environment of Drosophila melanogaster, testing individual flies and dyads (female-male, female-female and male-male pairs).
In these social contexts we measured individual and population asymmetries in individual behaviors (circling asymmetry, wing use) and dyadic behaviors (relative position and orientation between two flies) in five different genotypes.
We reasoned that if coordination between individuals drives alignment of behavioral asymmetries, greater alignment at the population-level should be observed in social contexts compared to solitary individuals.
We observed that the presence of other individuals influenced the behavior and position of flies but had unexpected effects on individual and population asymmetries: individual-level asymmetries were strong and modulated by the social context but population-level asymmetries were mild or absent.
Moreover, the strength of individual-level asymmetries differed between strains, but this was not the case for population-level asymmetries.
These findings suggest that the degree of social interaction found in Drosophila is insufficient to drive population-level behavioral asymmetries. | 212,654,604 |
Title:
Strong selective effects of mitochondrial DNA on the nuclear genome
Abstract:
Significance Efficient ATP synthesis requires the coordinated functions of proteins and RNAs produced from both the nuclear and mitochondrial genomes.
However, the importance of coevolution between the genomes in maintaining these interactions is highly debated.
Here we assess the role of coevolution within populations by comparing the nuclear and mitochondrial genotypes of high- and low-fitness hybrids between genetically divergent populations of a marine copepod.
High-fitness hybrids demonstrated elevated mitochondrial adenosine triphosphate synthesis and large biases for nuclear alleles from the same population as their mitochondrial genome.
These results suggest that selection strongly favors coevolved mitochondrial and nuclear genes in natural populations.
Disruption of mitonuclear compatibility, as may occur during secondary contact between populations, results in substantial reductions in hybrid fitness.
Oxidative phosphorylation, the primary source of cellular energy in eukaryotes, requires gene products encoded in both the nuclear and mitochondrial genomes.
As a result, functional integration between the genomes is essential for efficient adenosine triphosphate (ATP) generation.
Although within populations this integration is presumably maintained by coevolution, the importance of mitonuclear coevolution in key biological processes such as speciation and mitochondrial disease has been questioned.
In this study, we crossed populations of the intertidal copepod Tigriopus californicus to disrupt putatively coevolved mitonuclear genotypes in reciprocal F2 hybrids.
We utilized interindividual variation in developmental rate among these hybrids as a proxy for fitness to assess the strength of selection imposed on the nuclear genome by alternate mitochondrial genotypes.
Developmental rate varied among hybrid individuals, and in vitro ATP synthesis rates of mitochondria isolated from high-fitness hybrids were approximately two-fold greater than those of mitochondria isolated from low-fitness individuals.
We then used Pool-seq to compare nuclear allele frequencies for high- or low-fitness hybrids.
Significant biases for maternal alleles were detected on 5 (of 12) chromosomes in high-fitness individuals of both reciprocal crosses, whereas maternal biases were largely absent in low-fitness individuals.
Therefore, the most fit hybrids were those with nuclear alleles that matched their mitochondrial genotype on these chromosomes, suggesting that mitonuclear effects underlie individual-level variation in developmental rate and that intergenomic compatibility is critical for high fitness.
We conclude that mitonuclear interactions can have profound impacts on both physiological performance and the evolutionary trajectory of the nuclear genome. | 212,664,200 |
Title:
Structure-based mechanism of preferential complex formation by apoptosis signal–regulating kinases
Abstract:
SAM domains mediate heterotypic and homotypic interactions between ASK family kinases.
ASKs cooperate to signal Kinases of the ASK family trigger the activation of mitogen-activated protein kinase (MAPK) cascades in response to stresses, such as oxidative damage and inflammation.
Oligomerization of ASK proteins is key to their function, and they are potential therapeutic targets.
Trevelyan et al. identified sterile-alpha motif (SAM) domains in the carboxy-terminus of each human ASK protein that drove oligomerization.
Solving the crystal structure of the ASK3 SAM domain together with structural and biochemical assays of all three ASKs showed that ASK1 and ASK2 preferentially formed hetero-oligomers, whereas ASK3 preferentially formed homo-oligomers.
Disrupting interactions between the SAM domains reduced stress-induced ASK activity.
These findings emphasize the importance of taking these heterotypic interactions into account when developing strategies to target ASK proteins.
Apoptosis signal–regulating kinases (ASK1, ASK2, and ASK3) are activators of the p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways.
ASK1–3 form oligomeric complexes known as ASK signalosomes that initiate signaling cascades in response to diverse stress stimuli.
Here, we demonstrated that oligomerization of ASK proteins is driven by previously uncharacterized sterile-alpha motif (SAM) domains that reside at the carboxy-terminus of each ASK protein.
SAM domains from ASK1–3 exhibited distinct behaviors, with the SAM domain of ASK1 forming unstable oligomers, that of ASK2 remaining predominantly monomeric, and that of ASK3 forming a stable oligomer even at a low concentration.
In contrast to their behavior in isolation, the ASK1 and ASK2 SAM domains preferentially formed a stable heterocomplex.
The crystal structure of the ASK3 SAM domain, small-angle x-ray scattering, and mutagenesis suggested that ASK3 oligomers and ASK1-ASK2 complexes formed discrete, quasi-helical rings through interactions between the mid-loop of one molecule and the end helix of another molecule.
Preferential ASK1-ASK2 binding was consistent with mass spectrometry showing that full-length ASK1 formed hetero-oligomeric complexes incorporating large amounts of ASK2.
Accordingly, disrupting the association between SAM domains impaired ASK activity in the context of electrophilic stress induced by 4-hydroxy-2-nonenal (HNE).
These findings provide a structural template for how ASK proteins assemble foci that drive inflammatory signaling and reinforce the notion that strategies to target ASK proteins should consider the concerted actions of multiple ASK family members. | 212,667,320 |
Title:
Osteogenesis imperfecta and combined orthodontics and orthognathic surgery: a case report on two siblings
Abstract:
Osteogenesis imperfecta is a heterogeneous group of connective tissue diseases that is predominantly characterized by bone fragility and skeletal deformity.
Two siblings with undiagnosed type I osteogenesis imperfecta underwent orthognathic surgery for the treatment of facial asymmetry and mandibular prognathism.
The authors report two cases of combined orthodontics and orthognathic surgery in patients with type I osteogenesis imperfecta, mandibular prognathism, and facial asymmetry. | 212,667,793 |
Title:
Comparing an automated high-definition oblique camera system to rear-seat-observers in a wildlife survey in Tsavo, Kenya: Taking multi-species aerial counts to the next level
Abstract:
Abstract In aerial wildlife counts, human observers often fail to detect animals.
We conducted a multi-species sample-count in Tsavo National Park, Kenya, with traditional rear-seat-observers (RSOs) and an automated ‘oblique-camera-count’ (OCC) imaging system to compare estimates of 23 wildlife species derived from these two survey methods.
An aerial Total Count of elephant, buffalo and giraffe, conducted a month previously, provided a further comparison.
In the Tsavo Core (9560 km2), which harbours 80% of Tsavo’s elephants, the OCC system acquired 81 000 images for interpretation, of which 67 000 were obtained in parallel with RSO-counting along 3004 km of flight line.
The Tsavo outer blocks (24 171 km2) were surveyed using the OCC system without RSOs to acquire a further 84 000 images.
A random sample of 11 553 images were re-interpreted to derive species-specific probabilities of detection and correction factors.
Using ‘Jolly II’, non-parametric and Bayesian analyses, and applying correction factors, we demonstrate that the RSOs did not detect 14% of elephants, 60% of giraffe, 48% of zebra and 66% of the large antelopes.
For comparison, the Total Count observers did not detect 27% of elephant, 33% of buffalo, 57% of giraffe and 85% of carcasses.
The OCC method raises the elephant population estimate to 16 681 ± 4047 (95% cl) from the 12 722 counted in the Total Count (Z = 1.917, p = .0276).
These results suggest that RSO-based methods have significantly undercounted wildlife populations.
To align with improved counting methods, previous results need to be re-calibrated. | 212,670,903 |
Title:
Contemporary surgical approaches for hip resurfacing
Abstract:
Hip resurfacing and total hip arthroplasty have evolved and improved dramatically as surgical procedures in the last decade; allowing for improvement of patient function and quality of life.
A better understanding of biomaterials, biomechanics; as well as, surgical approaches have minimized time to recovery, improved implants’ survival and decreased complications.
In particular hip resurfacing as a bone conservation technique, has specific considerations when selecting the surgical approach and surgical instruments affecting the success of the surgery and the outcome in the young, active patient.
We present a review of surgical approaches for hip resurfacing, considering that these approaches are also performed for total hip arthroplasty, however they are adjusted or modified for hip resurfacing with special considerations to preserving femoral head blood supply as well as proper component orientation. | 212,673,829 |
Title:
Hypothesis: Chemical activity regulates and coordinates the processes maintaining glycerophospholipid homeostasis in mammalian cells
Abstract:
Mammalian cells maintain the complex glycerophospholipid (GPL) class compositions of their various membranes within close limits because this is essential to their well-being or viability.
Surprisingly, however, it is still not understood how those compositions are maintained except that GPL synthesis and degradation are closely coordinated.
Here, we hypothesize that abrupt changes in the chemical activity of the individual GPL classes coordinate synthesis and degradation as well other the homeostatic processes.
We have previously proposed that only a limited number of "allowed" or "optimal" GPL class compositions exist in cellular membranes because those compositions are energetically more favorable than others, that is, they represent local free energy minima (Somerharju et al 2009, Biochim. Biophys.
Acta 1788, 12-23).
This model, however, could not satisfactorily explain how the "optimal" compositions are sensed by the key homeostatic enzymes, that is, rate-limiting synthetizing enzymes and homeostatic phospholipases.
We now hypothesize that when the mole fraction of a GPL class exceeds an optimal value, its chemical activity abruptly increases which (a) increases its propensity to efflux from the membrane thus making it susceptible for hydrolysis by homeostatic phospholipases; (b) increases its potency to inhibit its own biosynthesis via a feedback mechanism; (c) enhances its conversion to another glycerophospholipid class via a novel process termed "head group remodeling" or (d) enhances its translocation to other subcellular membranes.
In summary, abrupt change in the chemical activity of the individual GPL classes is proposed to regulate and coordinate those four processes maintaining GPL class homeostasis in mammalian cells. | 212,677,792 |
Title:
Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors
Abstract:
This study demonstrates the potential utility of BET and MEK inhibitors for advanced MYCN-expressing triple-negative breast cancer.
BETting on combination treatment MYCN is a well-known oncogene that plays a role in cancer aggressiveness, but it is typically associated with neuroendocrine cancers.
Schafer et al. found a role for MYCN in triple-negative breast cancer, a particularly aggressive form of the disease, and identified a potential intervention.
Although there is no standard way to target MYCN directly, the authors determined that a group of experimental drugs called BET inhibitors are effective against triple-negative breast cancers that overexpress MYCN, especially when coupled with the inhibition of MEK, another known oncogene.
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that does not respond to endocrine therapy or human epidermal growth factor receptor 2 (HER2)–targeted therapies.
Individuals with TNBC experience higher rates of relapse and shorter overall survival compared to patients with receptor-positive breast cancer subtypes.
Preclinical discoveries are needed to identify, develop, and advance new drug targets to improve outcomes for patients with TNBC.
Here, we report that MYCN, an oncogene typically overexpressed in tumors of the nervous system or with neuroendocrine features, is heterogeneously expressed within a substantial fraction of primary and recurrent TNBC and is expressed in an even higher fraction of TNBCs that do not display a pathological complete response after neoadjuvant chemotherapy.
We performed high-throughput chemical screens on TNBC cell lines with varying amounts of MYCN expression and determined that cells with higher expression of MYCN were more sensitive to bromodomain and extraterminal motif (BET) inhibitors.
Combined BET and MEK inhibition resulted in a synergistic decrease in viability, both in vitro and in vivo, using cell lines and patient-derived xenograft (PDX) models.
Our preclinical data provide a rationale to advance a combination of BET and MEK inhibitors to clinical investigation for patients with advanced MYCN-expressing TNBC. | 212,677,934 |
Title:
Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy
Abstract:
DCs are critical cellular targets of PD-L1 blockade in cancer treatment.
Checkpoint musical chairs Anti–PD-1 or PD-L1 antibodies can reinvigorate antitumor immunity in a subset of patients with cancer.
To better understand the mechanisms behind successful therapy, Mayoux et al. characterized various ligands on the surface of dendritic cells (DCs).
PD-L1 on DCs can bind B7.1 on the same cell, potentially preventing PD-1 ligation on T cells or B7.1 ligation of its partner CD28.
They saw that PD-L1 was expressed in excess of B7.1, likely preventing T cell stimulation through these two pathways.
Patients with a high DC signature before treatment were more likely to respond to PD-L1 blockade.
These results reveal that in cis interactions on DCs have immunological and likely clinical consequences for checkpoint blockade therapy.
PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers.
Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity.
Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target of PD-L1 blocking antibody.
PD-L1 binds two receptors, PD-1 and B7.1 (CD80).
PD-L1 is expressed much more abundantly than B7.1 on peripheral and tumor-associated DCs in patients with cancer.
Blocking PD-L1 on DCs relieves B7.1 sequestration in cis by PD-L1, which allows the B7.1/CD28 interaction to enhance T cell priming.
In line with this, in patients with renal cell carcinoma or non–small cell lung cancer treated with atezolizumab (PD-L1 blockade), a DC gene signature is strongly associated with improved overall survival.
These data suggest that PD-L1 blockade reinvigorates DC function to generate potent anticancer T cell immunity. | 212,678,130 |
Title:
Neuroprotective actions of cerebellar and pineal allopregnanolone on Purkinje cells
Abstract:
The brain produces steroids de novo from cholesterol, so-called "neurosteroids." The Purkinje cell, a cerebellar neuron, was discovered as a major site of the biosynthesis of neurosteroids including sex steroids, such as progesterone, from cholesterol in the brain.
Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on the Purkinje cell to prevent cell death of this neuron.
Recently, the pineal gland was discovered as an important site of the biosynthesis of neurosteroids.
Allopregnanolone, a major pineal neurosteroid, acts on the Purkinje cell for the survival of this neuron by suppressing the expression of caspase-3, a crucial mediator of apoptosis.
This review summarizes the discovery of cerebellar and pineal allopregnanolone and its neuroprotective action on Purkinje cells. | 212,678,410 |
Title:
Volumetric cine magnetic resonance imaging (VC-MRI) using motion modeling, free-form deformation and multi-slice undersampled 2D cine MRI reconstructed with spatio-temporal low-rank decomposition.
Abstract:
Background ::: The purpose of this study is to improve on-board volumetric cine magnetic resonance imaging (VC-MRI) using multi-slice undersampled cine images reconstructed using spatio-temporal k-space data, patient prior 4D-MRI, motion modeling (MM) and free-form deformation (FD) for real-time 3D target verification of liver and lung radiotherapy. ::: ::: ::: Methods ::: A previous method was developed to generate on-board VC-MRI by deforming prior MRI images based on a MM and a single-slice on-board 2D-cine image.
The two major improvements over the previous method are: (I) FD was introduced to estimate VC-MRI to correct for inaccuracies in the MM; (II) multi-slice undersampled 2D-cine images reconstructed by a k-t SLR reconstruction method were used for FD-based estimation to maintain the temporal resolution while improving the accuracy of VC-MRI.
The method was evaluated using XCAT lung simulation and four liver patients' data. ::: ::: ::: Results ::: For XCAT, VC-MRI estimated using ten undersampled sagittal 2D-cine MRIs resulted in volume percent difference/volume dice coefficient/center-of-mass shift of 9.77%±3.71%/0.95±0.02/0.75±0.26 mm among all scenarios based on estimation with MM and FD.
Adding FD optimization improved VC-MRI accuracy substantially for scenarios with anatomical changes.
For patient data, the mean tumor tracking errors were 0.64±0.51, 0.62±0.47 and 0.24±0.24 mm along the superior-inferior (SI), anterior-posterior (AP) and lateral directions, respectively, across all liver patients. ::: ::: ::: Conclusions ::: It is feasible to improve VC-MRI accuracy while maintaining high temporal resolution using FD and multi-slice undersampled 2D cine images for real-time 3D target verification. | 212,684,843 |
Title:
Effect of pelvimetric diameters on success of surgery in patients submitted to robot-assisted perineal radical prostatectomy
Abstract:
OBJECTIVE ::: Minimally invasive techniques are used increasingly by virtue of advancements in technology.
Surgery for prostate cancer, which has high morbidity, is performed with an increasing momentum based on the successful oncological and functional outcomes as well as cosmetic aspects. ::: ::: ::: MATERIALS AND METHODS ::: 62 patients underwent robot-assisted perineal radical prostatectomy (R-PRP) surgery at our clinic between November 2016 and August 2017.
Six pelvimetric dimensions were defined and measured by performing multiparametric magnetic resonance imaging (mpMRI) prior to operation in all patients.
In light of these data, we aimed to investigate the effect of pelvimetric measurements on surgery duration and surgical margin positivity. ::: ::: ::: RESULTS ::: By using this technique in pelvic area, we observed that measurements only representing surgical site and excluding other pelvic organs had a significant effect on surgery duration, and pelvic dimensions had no significant effect on surgical margin positivity. ::: ::: ::: CONCLUSION ::: In R-PRP technique, peroperative findings and oncological outcomes can vary depending on several variable factors, but although usually not taken into account, pelvimetric measurements can also affect these outcomes.
However, there is a need for randomised controlled trials to be conducted with more patients. | 212,693,575 |
Title:
Energy-based devices for hemostasis in thyroid surgery
Abstract:
The evolution of operative techniques in thyroid surgery that has taken place over the past several decades would not have been possible if not for a sui generis revolution in surgery at the turn of the 19th and 20th centuries.
The three most important events of the end of the 19th century, i.e., the introduction of anesthesia, the use of artery forceps and ligation of blood vessels, as well as prophylactic management of perioperative infections decidedly affected the improvement of therapeutic results of thyroid surgery.
Surgical treatment of thyroid diseases is associated with the possibility of complications developing, of which bleeding is among the most serious ones, starting from the need for an immediate reoperation and ending at a considerable damage to functionally important structures: the laryngeal nerves and parathyroid glands.
The consensus reached between the development of science and progress in modern technologies has provided the basis for introducing and popularizing minimally invasive procedures, including operations using the approach through natural body openings.
Such an unprecedented development of surgical techniques would not be possible without devices for closing blood vessels.
Given the mechanism of hemostasis, current vascular sealing devices can generally be divided into three groups: ultrasonic, bipolar- radiofrequency and hybrid systems combining both energy modalities.
While analyzing the innovative, advanced technology of all the energy-based devices, it should be stated that only if they are used in a safe manner, quality of life of patients with various thyroid conditions is improved.
The employment of such devices fully confirms their usefulness; nevertheless, all the advantages should never release the surgeon from the obligation to appropriately and safely identify the surrounding structures and let him uncritically use the new device. | 212,694,043 |
Title:
The Effect of Intermittent Negative Pressure on the Amputation Stump of Adult Mice: A Pilot Study
Abstract:
Overview: Limb amputation could occur accidently or due to an inevitable medical indication such as cancer, vascular damage, or traumatic destruction.
Whatever the cause, a lost limb does not regenerate in mammals and most animals; however, studies showed that young mice have an ability to restore a distally amputated finger tip.
There are evidences the in literature supporting that applying intermittent negative pressure to tissues could trigger the release of growth factors; which are important for tissue regeneration. ::: Objectives: To document the effects of the intermittent negative pressure-INP in an amputation stump of albino mice, particularly if there are evidence of cellular proliferation or tissue remodeling. ::: Methods: Two albino mice, three weeks of age, were first cut at the wrist level on their right arms.
One mouse was subjected to manual INP by a fifty milliliter pump syringe, ten minutes daily for three weeks, the other mouse left to heal spontaneously, as a control.
::: Results: There was an excessive fibrous tissue formation within the stump, seen by the naked eye.
Microscopic examination showed thinning of the epithelial lining, areas of fluid and inflammatory cells collection, and excessive fibrous tissue formation. ::: Conclusion: Negative pressure does not enhance the growth or regeneration of amputated limbs in adult mice; instead, it caused an inflammatory-like response and fibrous tissue formation. | 212,694,640 |
Title:
Prevalence of metabolic syndrome and its different components in patients with acute coronary syndrome
Abstract:
Background: Several components of the Metabolic Syndrome (MetS) are risk factor for cardiovascular diseases.
So, this study was conducted to evaluate the prevalence of MetS and its components in patients with CAD.
Methods: Author included all patients admitted with Acute Coronary Syndrome (ACS), who had CAD confirmed by coronary angiography.
They were divided into two groups according to presence or absence of MetS based on International Diabetes Federation criteria.
The prevalence of MetS and its individual components was estimated.
Results: It was observed that there is a high prevalence of MetS (66%) in patients admitted with ACS.
Metabolic syndrome is more prevalent in female patients (82.4%) than in male patients (57.6%) with ACS.
Hypertension is the most prevalent (87.9) component of MetS. Diabetes Mellitus (DM) is the 2 nd most prevalent (83.3%) component of MetS. About 65.2% patients with MetS had abnormally raised triglyceride levels and 32(48.5%) had abnormally low HDL-cholesterol level.
Among the MetS 38(57.6%) had abnormal waist circumference.
Among the study group, the most common triad of MetS components was DM + HTN + abnormal TG.
There is significant association between MetS and microalbuminuria, with incidence of 22(33.3%) in this study.
Similarly, a significant association between DM and microalbuminuria, 23(33.8%) was observed.
Conclusions: This study confirms a very high prevalence of MetS in Indian patients with CAD.
The prevalence of the risk factors was higher in CAD patients with MetS. | 212,695,906 |
Title:
Antibiogram of Clinical Isolates of Staphylococcus Aureus from a Tertiary Care Centre
Abstract:
Background: Staphylococcus aureus causes wide variety of infections.
Methicillin resistant Staphylococcus aureus (MRSA) is of a great concern.
It has developed resistance to non β-lactam antibiotics also and its treatment should be guided by antibiotic susceptibility testing. ::: Aim: To study the antibiotic susceptibility pattern of clinical isolates of Staphylococcus aureus.
::: Material & methods: A total of 300 clinical isolates of S. aureus were subjected to antimicrobial susceptibility testing by modified Kirby Bauer disc diffusion method as per the CLSI guidelines.
MIC for vancomycin and linezolid was performed by agar dilution method. ::: Results: Most of the strains of S. aureus were resistant to penicillin and methicillin resistance was as high as 35%.
Resistance to non β-lactam antibiotics was found to be significantly more in MRSA strains as compared to methicillin sensitive S. aureus (MSSA).
For prevention of increase in resistance, appropriate use of antibiotics guided by antibiotic sensitivity is necessary. | 212,696,020 |
Title:
Primary hyperparathyroidism and hypertension.
Abstract:
Although untreated primary hyperparathyroidism is associated with increased cardiovascular mortality, controversy exists regarding the therapeutic effects of parathyroidectomy on cardiovascular health.
This review will examine the evidence linking primary hyperparathyroidism (PHPT) and cardiovascular disease, specifically hypertension, and evaluate the available literature regarding the natural history of hypertension after successful parathyroidectomy. | 212,696,637 |
Title:
“Signs are Brisk when Nutrients at risk, act fast before last!!”: A study on Impact of Nutritional Intake on Clinical Manifestation
Abstract:
The present study explored the impact of nutritional intake on clinical manifestation.
Physical signs and symptoms of malnutrition can be valuable aids in detecting nutritional deficiencies.
Protein and micro nutrient deficiency have been the major nutritional problems faced by developing countries such as India.
This study was conducted among 1000 students.
The samples are selected by means of stratified sampling and simple random sampling techniques.
Adopting Anthropometry (Waist circumference, Hip circumference, Waist to Hip ratio), Biochemical (Hemoglobin using Drabki method, Clinical, and Dietary details (Food frequency, three day dietary record) were obtained from the subjects by appropriate methods.
The obtained details were coded and entered into Microsoft excel.
The coded raw data were subjected to statistical analysis using Statistical Package for Social Science (SPSS) version 20.0.
Anthropometry, biochemical, clinical, dietary details were correlated and results were interpreted.
The effect of low hemoglobin on clinical manifestation was observed in the present study.
It demonstrated that low hemoglobin levels resulted in a number of manifestations such as hairloss, recurrent mouth ulcer, angular stomatitis, glossitis, depression, irritability, poor concentration.
Overweight and obese subjects manifested with acanthosis nigricans, whereas underweight subjects reported to have loss of appetite, loss of taste, poor concentration, irritability and recurrent mouth ulcer.
Subjects with increased waist circumference, hip circumference, and waist to hip ratio were presented with the symptoms of acanthosis nigricans and goiter.
Thus it is essential for the college students to consume nutrient rich foods and avoid energy densed food to maintain adequate nutritional status and prevent deficiencies. | 212,701,053 |
Title:
Systemic ventricular strain and torsion are predictive of elevated serum NT-proBNP in Fontan patients: a magnetic resonance study.
Abstract:
Background ::: This study aimed to investigate the associations between cardiac strain, cardiac torsion, ventricular volumes, and ventricular ejection fraction, with N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in Fontan patients who were age- and gender-matched with healthy control subjects. ::: ::: ::: Methods ::: Cardiovascular magnetic resonance (CMR) studies performed in 22 (15 male, 7 female) patients with single-ventricle physiology (all morphological left ventricles) palliated with Fontan and 17 (10 male, 7 female) age- and gender-matched healthy children volunteers were retrospectively analyzed.
Serum NT-proBNP levels were obtained in Fontan subjects.
Standard post-processing of CMR images included systemic ventricular end-diastolic and end-systolic volumes, stroke volume, cardiac mass, atrioventricular regurgitation, and ejection fraction.
CMR tissue tracking (TT) software was used to quantify global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) and torsion of the systemic ventricle.
Pearson and Spearman correlation coefficients were used in comparisons of correlations between NT-proBNP and functional parameters in repair Fontan patients.
Intra-observer and inter-observer variability of CMR strain and torsion values were determined from 10 randomly selected Fontan subjects and 10 randomly selected control subjects.
::: ::: ::: Results ::: GLS was significantly lower in Fontan patients than in control subjects (-15.19±2.94 vs. -19.97±1.70; P<0.001).
GLS was not significantly different between normal NT-proBNP levels and high NT-proBNP levels in Fontan patients (-15.59±2.72 vs. -14.62±3.32; P=0.462).
The GCS of repair Fontan patients was not significantly lower than that of the control group (-16.76±3.27 vs. -17.88±2.26; P=0.235).
GCS was significantly different between normal and high NT-proBNP levels group in Fontan patients (-17.95±2.43 vs. -15.04±3.67; P=0.036).
The peak systolic torsion and peak systolic torsion rates were significantly lower in Fontan patients than in control subjects (0.81±0.41 vs. 1.07±0.36, P=0.044; 7.36±3.41 vs. 9.85±2.61, P=0.017).
Peak systolic torsion was significantly lower in Fontan patients with normal NT-proBNP levels than in high NT-proBNP subjects (0.67±0.43 vs. 1.01±0.29; P=0.036).
GCS and torsion were more strongly correlated with NT-proBNP in the patient group (r=0.541 for GCS; r=0.588 for torsion, P<0.01).
The parameters of strain and torsion could be reproduced with sufficient accuracy by intra-observer agreement(biases =0.04 for GLS; biases =0.66 for GCS; biases =1.03 for GRS; biases =0.04 for torsion) and inter-observer agreement (biases =0.32 for GLS; biases =0.85 for GCS; biases =1.52 for GRS; biases =0.18 for torsion). ::: ::: ::: Conclusions ::: GLS is an earlier marker of contractile dysfunction in repair Fontan patients.
Peak systolic torsion may be a biomarker for determining subclinical dysfunction, as it is more strongly correlated with serum biomarkers of ventricular function than ventricular size or ejection fraction. | 212,701,091 |
Title:
COVID-19 spike-host cell receptor GRP78 binding site prediction
Abstract:
ObjectivesUnderstanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives.
The spike protein of coronaviruses is the main driving force for host cell recognition. | 212,709,012 |
Title:
The expression of apolipoproteina1 and its correlation with infiltration of urologic neoplasm
Abstract:
Background: To explore the differential expression of apolipoproteinA1 (APOA1) in urologic neoplasm patient compared with controls, as well as investigates whether APOA1 correlated with infiltration of urologic neoplasm. ::: Methods: A total of 59 tissue sections of surgically-resected urologic neoplasm and 6 cases of normal tissue sections were collected.
Fourteen cases of urine samples from transitional cell carcinoma patients and 6 cases urine samples from controls were also applied in this experiment.
We also selected 6 cases of fresh bladder transitional cell carcinoma tissues.
The urologic neoplasm tissue sections were classified into infiltration and non-infiltration urologic neoplasm groups.
The expressions of APOA1 between urologic neoplasm and normal control were detected by Western blot, Immunohistochemistry and qRT-PCR.
The method of Immunohistochemistry was applied to examine the differences of APOA1 expression between infiltration and non-infiltration urologic neoplasm tissue section groups.
::: Results: Compared with none expression in normal controls, APOA1 was exhibited higher level in urologic neoplasm patient’s urine and fresh bladder transitional cell carcinoma tissues (P Conclusions: APOA1 could act as a valuable biomarker for predicting the occurrence and development of urologic neoplasm. | 212,711,501 |
Title:
Determination of Color and Heat Level of Some Resistance Sources and Improved Pepper Genotypes
Abstract:
Background: In this study, the capsaicin content, heat level and color of nine pepper genotypes and varieties belonging to Capsicum annuum and Capsicum chinense were described at different ripening stages.
Heat level and color is a desirable feature for Turkish pepper consumers.
Therefore, knowledge on the heat level and of Turkish pepper genotypes is important for a future breeding project aiming variety development. ::: Methods: Turkish materials (Alata 10, 15 and 111) were improved from the pepper collection of Alata Horticultural Research Institute-Turkey.
The Rwandan variety Pili-Pili is consumed in Rwandan cuisine.
The capsaicin content of the Alata collection and Pili-Pili were identified both at immature and red ripening stages.
In addition, some accessions carrying various resistances to diseases were evaluated: namely Er-Fu-Tou (Cucumber Mosaic Virus), C29 (Phytophthora capsici and Potato Virus Y), PI 260429 (Tobacco Mosaic Virus) and PI 152225 (Tomato spotted wilt virus); for these accessions, sampling was done at red ripening stage.
High-performance liquid chromatography (HPLC) was used for identifying capsaicinoids and extraction was performed by sodium acetate saturated ethanol.
ASTA 20.0 method was applied to measure the extractable color of improved lines.
::: Results: ::: •Results demonstrated that there was considerable variation among genotypes. ::: •The highest capsaicin content and heat level were detected in the genotype PI 152225.
For dihydrocapsaicin content, Er-Fu-Tou variety was the first and followed by PI 260429 and PI 152225. ::: •Heat level in pepper involves the relationship between capsaicin and dihydrocapsaicin and therefore, it is important to convert to the Scoville Heat Unit (SHU).
The most pungent genotype PI 152225 was followed by Pili-Pili variety (red stage), Er-Fu-Tou, Rwandan Pili-Pili variety (immature stage), Alata 111 (red stage) and PI 260429. ::: •The highest ASTA value was detected in mature fruits of Er-Fu-Tou genotype with 217 ASTA color value and it was followed by improved line Alata 111 from Kahramanmaras pepper population with 173 ASTA. ::: Conclusions: At the end of study, Er-Fu-Tou (CMV resistant) and PI 152225 (TSWV resistant) lines were found to be useful to improve varieties having both quality properties and resistance to diseases from the Kahramanmaras red pepper population via short term breeding program while they were not suitable to improve sweet pepper with rapid breeding program.
Rwandan variety Pili-Pili was not found appropriate to improve varieties producing high quality dried pepper. | 212,713,004 |
Title:
Clinical significance of PI3 and HLA-DOB as potential prognostic predicators for ovarian cancer
Abstract:
Background: The outcomes of ovarian cancer patients are very poor, therefore it is necessary to find prognostic biomarkers and explore the potential underlying molecular mechanisms of ovarian cancer.
Methods: In this study, a gene expression microarray data set covering 562 ovarian serous cystadenocarcinomas and 12,042 genes was downloaded from The Cancer Genome Atlas (TCGA) database.
For each candidate gene, samples were allocated into a “high group” or a “low group” according to the expression level.
The overall survival (OS) rates were compared between the two groups.
Then, a univariate analysis and a multivariate Cox proportional hazards test were carried out to examine the associations between genes and multiple clinicopathological parameters.
::: Results: Among all candidate genes, PI3 (peptidase inhibitor 3, often called elafin) and HLA-DOB (major histocompatibility complex, class II, DO beta) were identified as hub genes.
PI3 (P=7.99e-7) and HLA-DOB (P=7.52e-6) showed significant associations with OS, especially in patients with stage III or IV disease.
Both PI3 (HR =1.84, P=3.77e-7) and HLA-DOB (HR =0.68, P=0.001134) were identified as independent predictors of ovarian cancer patients OS.
In addition, IRF1 (interferon regulatory factor 1) (P=1.16e-15) and SPI1 (Spi-1 proto-oncogene) (P=2.03e-6) were identified as the most significant transcription factors.
Conclusions: Our data indicate that PI3 and HLA-DOB are potential biomarkers that could be used to predict the prognosis of ovarian cancer patients, and may play important roles in ovarian cancer progression.
Further experimental and clinical studies with larger sample sizes are needed to confirm these findings. | 212,713,060 |
Title:
Prevalence of premenopausal osteoporosis in hypothyroid patients
Abstract:
Background: Hypothyroidism alone is not a risk factor for osteoporosis but the patient on treatment with levothyroxine in chronic terms have the greater chances of osteoporosis.
This study is to evaluate the role of chronic levo-thyroxine treatment on bone mineral density and the development of osteoporosis.
Methods: A cross sectional descriptive study in which patients with recently diagnosed as hypothyroidism were taken as the first group and the second group as those who were having hypothyroidism for more than 2 years plus on chronic treatment with levothyroxine.
Healthy premenopausal women were the control group.
TSH was measured in all and the T score were used to measure osteoporosis severity.
T score of lumbar vertebra and neck of femur were used for comparison.
The description of qualitative data was done in absolute frequencies and percentages.
The description of quantitative data were done as the, mean standard deviation, median, minimum and maximum.
In the comparison of qualitative data between groups, the Chi-square test and contingency tables was used by rearranging the percentages of several variables (TSH, t-score).
The statistical significance was set p<0.05.
Results: TSH levels in the first group were slightly different from rest of the groups.
T score were significantly lesser in patients in the second group who are diagnosed with hypothyroidism and on treatment with levothyroxine.
Conclusions: The treatment for hypothyroidism with levo thyroxine reduces both TSH and bone mineral density in the study groups.
Proper control of risk factors and avoidance of high dose thyroxine supplements are an effective way in prevention of osteoporosis. | 212,715,929 |
Title:
How asbestos and other fibers cause mesothelioma
Abstract:
Mesothelioma has long been associated with the exposure to asbestos, which was largely used in manufacturing activities.
Toxicology studies in vitro and in vivo demonstrated that asbestos fibers were carcinogenic, and epidemiology studies revealed that asbestos exposure was paralleled by the increase in the incidence of mesothelioma and related mortality rates.
More recently, the role of chronic inflammation and the molecular mechanisms involved in carcinogenesis by mineral fibers were elucidated following the discovery of the roles of HMGB1 and inflammasome.
A change of paradigm was the discovery of a prevalence of mesotheliomas attributable to inherited mutations of cancer susceptibility genes.
The discovery of BAP1 as a predisposition gene for the development of familial mesothelioma and other cancers implemented genome studies in patients with mesothelioma and routine clinical surveys in individuals at risk to identify germline mutations associated with cancers included in the BAP1 syndrome.
A further progress in the approach to asbestos-related malignancy was the adoption of combined genetics and environmental analyses according to the model of gene-environment (GxE) interactions.
This review aims at updating on the most recently discovered mechanisms of tumorigenesis and the pivotal role of GxE interactions. | 212,716,356 |
Title:
Knowledge, attitudes, and practices towards COVID-19 among Chinese residents during the rapid rise period of the COVID-19 outbreak: a quick online cross-sectional survey
Abstract:
Unprecedented measures have been adopted to control the rapid spread of the ongoing COVID-19 epidemic in China.
People's adherence to control measures is affected by their knowledge, attitudes, and practices (KAP) towards COVID-19.
In this study, we investigated Chinese residents' KAP towards COVID-19 during the rapid rise period of the outbreak.
An online sample of Chinese residents was successfully recruited via the authors' networks with residents and popular media in Hubei, China.
A self-developed online KAP questionnaire was completed by the participants.
The knowledge questionnaire consisted of 12 questions regarding the clinical characteristics and prevention of COVID-19.
Assessments on residents' attitudes and practices towards COVID-19 included questions on confidence in winning the battle against COVID-19 and wearing masks when going out in recent days.
Among the survey completers (n=6910), 65.7% were women, 63.5% held a bachelor degree or above, and 56.2% engaged in mental labor.
The overall correct rate of the knowledge questionnaire was 90%.
The majority of the respondents (97.1%) had confidence that China can win the battle against COVID-19.
Nearly all of the participants (98.0%) wore masks when going out in recent days.
In multiple logistic regression analyses, the COVID-19 knowledge score (OR: 0.75-0.90, P<0.001) was significantly associated with a lower likelihood of negative attitudes and preventive practices towards COVID-2019.
Most Chinese residents of a relatively high socioeconomic status, in particular women, are knowledgeable about COVID-19, hold optimistic attitudes, and have appropriate practices towards COVID-19.
Health education programs aimed at improving COVID-19 knowledge are helpful for Chinese residents to hold optimistic attitudes and maintain appropriate practices.
Due to the limited sample representativeness, we must be cautious when generalizing these findings to populations of a low socioeconomic status. | 212,716,487 |
Title:
Zoonotic origins of human coronaviruses
Abstract:
Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years.
Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold.
The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be.
The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well.
Most HCoVs originated from bats where they are non-pathogenic.
The intermediate reservoir hosts of some HCoVs are also known.
Identifying the animal hosts has direct implications in the prevention of human diseases.
Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans.
In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission.
Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination.
The current CoV disease 2019 (COVID-19) epidemic is discussed in this context.
In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted. | 212,716,807 |
Title:
Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study
Abstract:
Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food.
We evaluated CD patients reporting voluntary and occasional transgressions to their GFD.
From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled.
These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake.
Mortality was calculated and compared to the general population.
A group of patients on strict GFD (GFD-adherent) acted as controls.
One thousand three hundred seventy-eight CD patients were evaluated during the study period.
One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten.
The mean gluten intake was 185.2 ± 336.9 g/year, and the duration of their incorrect GFD was 8.6 ± 6.9 years.
Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients.
Seventy percent did not present any alteration at CE.
Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion.
Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers.
Mortality was not different between the groups and the general population.
Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached. | 212,718,891 |
Title:
A two-circular RNA signature of donor circFOXN2 and circNECTIN3 predicts early allograft dysfunction after liver transplantation
Abstract:
Background ::: Early allograft dysfunction (EAD) following liver transplantation is associated with poor recipient and graft survival.
In recent years, circular RNAs (circRNAs) have emerged as important components of endogenous RNAs.
This study aims to explore the expression profile and predictive value of graft circular RNAs for EAD after liver transplantation.
::: ::: ::: Methods ::: RNA sequencing was conducted to identify the circRNA profile in donor liver tissues.
Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify candidate circRNAs.
A novel model combining circular RNA signature was established to predict EAD based on the multivariate analysis.
::: ::: ::: Results ::: A total of 442 circRNAs were differentially expressed between the EAD and non-EAD groups, of which, 223 were significantly upregulated and 219 were downregulated in the EAD group (Fold change >2, P<0.05).
qRT-PCR validation indicated that circFOXN2 and circNECTIN3 levels in the EAD group were significantly lower than those in the non-EAD group (P=0.038, 0.024, respectively; n=115).
Among the 115 recipients, 32 recipients with high circFOXN2 expression were classified as circular RNA signature A and the rest recipients with low circFOXN2 expression were categorized into circular RNA signature B (n=33, high circNECTIN3 expression) and C (n=50, low circNECTIN3 expression).
The incidence rates of EAD in signature A, B and C were significantly different (3.1%, 21.2% and 42.0%, respectively; P=0.000).
According to the multivariate analysis, a novel predictive model for EAD was developed based on CIT (P=0.000) and circular RNA signature (P=0.013).
The novel model displayed a high predictive value for EAD with areas under the curve (AUC) of 0.870 (95% CI: 0.797-0.942). ::: ::: ::: Conclusions ::: Donor circFOXN2 and circNEXTIN3 were associated with the incidence of EAD.
The novel model combing the two-circular RNA signature had a high predictive value for EAD. | 212,728,380 |
Title:
Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals
Abstract:
In December 2019, a novel coronavirus (CoV) epidemic, caused by the severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) emerged from China.
This virus causes the coronavirus disease 2019 (COVID-19).
Since then, there have been anecdotal reports of ocular infection.
The ocular implications of human CoV infections have not been widely studied.
However, CoVs have been known to cause various ocular infections in animals.
Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models.
In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed.
The review article will also highlight animal CoVs and their associated ocular infections.
We hope that this article will serve as a start for further research into the ocular implications of human CoV infections. | 212,729,694 |
Title:
Near-infrared fluorescence in robotic thyroidectomy
Abstract:
New imaging techniques using near-infrared (NIR) fluorescence in combination with remote access thyroidectomy have been studied in endocrine surgery to determine their utility, with the goal of reducing potential complications.
Indocyanine green (ICG) imaging is a safe adjunct to remote access thyroid surgery.
Nevertheless, experience with ICG is limited, and the caveats surrounding the use of ICG imaging in conventional thyroid surgery exist in remote access surgery as well.
This report describes the various remote access techniques and considers the advantages and potential disadvantages of ICG in remote access thyroidectomy. | 212,730,451 |
Title:
The SARS-CoV-2 outbreak: what we know
Abstract:
There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020.
Governments are under increased pressure to stop the outbreak spiraling into a global health emergency.
At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities.
This information should include reports from outbreak site and from laboratories supporting the investigation.
This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus. | 212,731,388 |
Title:
Sepsis therapies: learning from 30 years of failure of translational research to propose new leads
Abstract:
Sepsis has been identified by the World Health Organization (WHO) as a global health priority.
There has been a tremendous effort to decipher underlying mechanisms responsible for organ failure and death, and to develop new treatments.
Despite saving thousands of animals over the last three decades in multiple preclinical studies, no new effective drug has emerged that has clearly improved patient outcomes.
In the present review, we analyze the reasons for this failure, focusing on the inclusion of inappropriate patients and the use of irrelevant animal models.
We advocate against repeating the same mistakes and propose changes to the research paradigm.
We discuss the long-term consequences of surviving sepsis and, finally, list some putative approaches-both old and new-that could help save lives and improve survivorship. | 212,731,396 |
Title:
Avian injury quantification using the Shoreline Deposition Model and model sensitivities
Abstract:
Deposition models, such as the Shoreline Deposition Model (SDM) used to quantify nearshore avian injuries resulting from the 2010 Deepwater Horizon (DWH) oil spill, were developed to improve the estimates of nearshore avian mortality resulting from the release of oil into coastal and marine environments.
Unlike earlier approaches to injury quantification, such as simple counts of carcasses on the shoreline, a modeling approach allows trustees to evaluate the precision of their estimate (i.e., to develop a confidence interval) and can inform decision-making and the likely utility of additional primary data collection activities through sensitivity analyses.
In this paper, we rely on published literature, actual DWH data, and a deposition model simulation to evaluate how different model inputs and assumptions can affect the accuracy and precision of model results.
We find that the precision of deposition models is strongly affected by the length of time between subsequent shoreline searches, the underlying magnitude of carcass deposition, carcass persistence probabilities, and carcass detection probabilities.
In addition, the accuracy of deposition model results may be affected by natural fluctuations in deposition rates.
Given these findings, we recommend that natural resource trustees include an evaluation of future model uncertainty as part of their initial data collection efforts.
This will allow them to deploy resources in a way that maximizes the utility of future deposition model results.
We also identify several factors that do not need to be assessed immediately following a spill event, thereby potentially freeing resources for more time critical data collection efforts. | 212,732,164 |
Title:
Day Level Forecasting for Coronavirus Disease (COVID-19) Spread: Analysis, Modeling and Recommendations
Abstract:
In mid of March 2020, Coronaviruses such as COVID-19 is declared as an international epidemic.
More than 125000 confirmed cases and 4,607 death cases have been recorded around more than 118 countries.
Unfortunately, a coronavirus vaccine is expected to take at least 18 months if it works at all.
Moreover, COVID -19 epidemics can mutate into a more aggressive form.
Day level information about the COVID -19 spread is crucial to measure the behavior of this new virus globally.
Therefore, this study presents a comparison of day level forecasting models on COVID-19 affected cases using time series models and mathematical formulation.
The forecasting models and data strongly suggest that the number of coronavirus cases grows exponentially in countries that do not mandate quarantines, restrictions on travel and public gatherings, and closing of schools, universities, and workplaces (Social Distancing). | 212,736,884 |
Title:
Braitenberg Vehicles as Developmental Neurosimulation
Abstract:
The connection between brain and behavior is a longstanding issue in the areas of behavioral science, artificial intelligence, and neurobiology.
Particularly in artificial intelligence research, behavior is generated by a black box approximating the brain.
As is standard among models of artificial and biological neural networks, an analogue of the fully mature brain is presented as a blank slate.
This model generates outputs and behaviors from a priori associations, yet this does not consider the realities of biological development and developmental learning.
Our purpose is to model the development of an artificial organism that exhibits complex behaviors.
We will introduce our approach, which is to use Braitenberg Vehicles (BVs) to model the development of an artificial nervous system.
The resulting developmental BVs will generate behaviors that range from stimulus responses to group behavior that resembles collective motion.
Next, we will situate this work in the domain of artificial brain networks.
Then we will focus on broader themes such as embodied cognition, feedback, and emergence.
Our perspective will then be exemplified by three software instantiations that demonstrate how a BV-genetic algorithm hybrid model, multisensory Hebbian learning model, and multi-agent approaches can be used to approach BV development.
We introduce use cases such as optimized spatial cognition (vehicle-genetic algorithm hybrid model), hinges connecting behavioral and neural models (multisensory Hebbian learning model), and cumulative classification (multi-agent approaches).
In conclusion, we will revisit concepts related to our approach and how they might guide future development. | 212,736,923 |
Title:
Association of serum ferritin with metabolic syndrome in eight cities in China
Abstract:
Objective ::: This study aims to evaluate the cross-sectional association of serum ferritin (SF) and the risk of metabolic syndrome (MetS) and its components among adults in eight cities in China. ::: ::: ::: Methods ::: Subjects were recruited using a combination of systematic cluster random sampling and purposive sampling in eight cities in China.
The sociodemographic characteristics, data of lifestyle factors, self-reported disease history, and 24-hr dietary intake were obtained using a validated questionnaire.
Anthropometry was performed, and fasting blood was collected to test the SF, fasting blood glucose (FBG), insulin, high-sensitivity C-reactive protein (hs-CRP), triglycerides (TG), and cholesterols.
Logistic and linear regression analyses were conducted to investigate the associations, adjusting for age, city level, smoking, drinking, weekly moderate-to-vigorous activity, dietary factors, hs-CRP, and BMI. ::: ::: ::: Results ::: Serum ferritin level is positively correlated with total cholesterol, TG, FBG, HOMA-IR, and hs-CRP after adjusting for age and BMI.
The odds ratio (OR) for MetS in the highest quartile of SF was 2.23 (1.32, 3.77) after adjusting for men, compared with the lowest quartile.
An elevated ferritin concentration was significantly related to hypertriglyceridemia (p < .001) and elevated glucose (p = .013) among men, but not among women.
Furthermore, compared with Q1, the OR for insulin resistance in the ferritin Q4 group was 3.08 (1.50, 6.32) among men and 1.96 (1.19, 3.24) among women. ::: ::: ::: Conclusion ::: A positive association between elevated SF and MetS and its components including hypertriglyceridemia and elevated glucose was found in multivariate analyses among men, and SF levels are independently associated with IR. | 212,739,457 |
Title:
Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs
Abstract:
The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives.
One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present.
Here, we develop a model of homing mechanisms parameterized by experimental studies.
Our model incorporates several factors affecting drives with multiple gRNAs, including timing of cleavage, reduction in homology-directed repair efficiency due to imperfect homology, Cas9 activity saturation, gRNA activity level variance, and incomplete homology-directed repair.
We find that homing drives have an optimal number of gRNAs, usually between two and eight, depending on the specific drive type and performance parameters.
These results contradict the notion that resistance rates can be reduced to arbitrarily low levels by gRNA multiplexing and highlight the need for combined approaches to counter resistance evolution in CRISPR homing drives. | 212,739,977 |
Title:
Changes in starch structures and in vitro digestion characteristics during maize (Zea mays L.) germination
Abstract:
This study analyzed changes in the starch structures and in vitro digestion profiles of a specific maize cultivar, Jike 728 (JK728), in Jilin, China, after 0-5 days of germination.
The total starch, amylose, and amylopectin contents decreased significantly during germination.
The average molecular weight of the starch compounds also decreased significantly during germination.
The proportion of amylopectin with a degree of polymerization (DP) of 13-24 significantly decreased, while the relative abundance of amylopectin with DP values of 6-12, 25-36, and 37-60 significantly increased.
The X-ray diffraction (XRD) patterns of all samples were characteristic of A-type starch, and the starch relative crystallinity decreased over time.
The proportions of slowly digestible starch and resistant starch decreased significantly, while the proportion of rapidly digestible starch increased significantly during germination.
Germination is an easy, inexpensive, and low-carbon processing method.
This study indicates that germination is an effective way to control the physical properties and digestibility of starch in maize.
The changes observed in the physical properties and digestibility of maize starch after germination provide scientists with a platform to understand starch modification mechanisms that might have potential applications on an industrial scale. | 212,740,747 |
Title:
New Perspectives on Atherogenic Dyslipidaemia and Cardiovascular Disease
Abstract:
Over the past few decades, atherogenic dyslipidaemia has become one of the most common phenotypic presentations of lipid abnormalities, being strongly and unequivocally associated with an increased risk of cardiovascular (CV) disease.
Despite the excellent results achieved from statin and non-statin management of LDL cholesterol and CV events prevention, there still remains a significant residual risk, associated with the prevalence of non-LDL cholesterol lipid patterns characterised by elevated triglyceride levels, low HDL cholesterol, a preponderance of small and dense LDL particles, accumulation of remnant lipoproteins and postprandial hyperlipidaemia.
These qualitative and quantitative lipid modifications are largely associated with insulin resistance, type 2 diabetes and obesity, the prevalence of which has grown to epidemic proportions throughout the world.
In this review, we analyse the pathophysiology of this particular dyslipidaemia, its relationship with the development of atherosclerotic CV disease and, finally, briefly describe the therapeutic approaches, including changes in lifestyle and current pharmacological interventions to manage these lipid alterations aimed at preventing CV events. | 212,741,285 |
Title:
Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia
Abstract:
OBJECTIVE.
The purpose of this study was to investigate early clinical and CT manifestations of coronavirus disease (COVID-19) pneumonia.
MATERIALS AND METHODS.
Patients with COVID-19 pneumonia confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test (reverse transcription-polymerase chain reaction) were enrolled in this retrospective study.
The clinical manifestations, laboratory results, and CT findings were evaluated.
RESULTS.
One hundred eight patients (38 men, 70 women; age range, 21-90 years) were included in the study.
The clinical manifestations were fever in 94 of 108 (87%) patients, dry cough in 65 (60%), and fatigue in 42 (39%).
The laboratory results were normal WBC count in 97 (90%) patients and normal or reduced lymphocyte count in 65 (60%).
High-sensitivity C-reactive protein level was elevated in 107 (99%) patients.
The distribution of involved lobes was one lobe in 38 (35%) patients, two or three lobes in 24 (22%), and four or five lobes in 46 (43%).
The major involvement was peripheral (97 patients [90%]), and the common lesion shape was patchy (93 patients [86%]).
Sixty-five (60%) patients had ground-glass opacity (GGO), and 44 (41%) had GGO with consolidation.
The size of lesions varied from smaller than 1 cm (10 patients [9%]) to larger than 3 cm (56 patients [52%]).
Vascular thickening (86 patients [80%]), crazy paving pattern (43 patients [40%]), air bronchogram sign (52 patients [48%]), and halo sign (69 [64%]) were also observed in this study.
CONCLUSION.
The early clinical and laboratory findings of COVID-19 pneumonia are low to midgrade fever, dry cough, and fatigue with normal WBC count, reduced lymphocyte count, and elevated high-sensitivity C-reactive protein level.
The early CT findings are patchy GGO with or without consolidation involving multiple lobes, mainly in the peripheral zone, accompanied by halo sign, vascular thickening, crazy paving pattern, or air bronchogram sign. | 212,741,586 |
Title:
Pressure Overload Is Associated With Low Levels of Troponin I and Myosin Binding Protein C Phosphorylation in the Hearts of Patients With Aortic Stenosis
Abstract:
In previous studies of septal heart muscle from HCM patients with hypertrophic obstructive cardiomyopathy (HOCM, LVOT gradient 50–120 mmHg) we found that the level of phosphorylation of troponin I (TnI) and myosin binding protein C (MyBP-C) was extremely low yet samples from hearts with HCM or DCM mutations that did not have pressure overload were similar to donor heart controls.
We therefore investigated heart muscle samples taken from patients undergoing valve replacement for aortic stenosis, since they have pressure overload that is unrelated to inherited cardiomyopathy.
Thirteen muscle samples from septum and from free wall were analyzed (LVOT gradients 30–100 mmHg)
The levels of TnI and MyBP-C phosphorylation were determined in muscle myofibrils by separating phosphospecies using phosphate affinity SDS-PAGE and detecting with TnI and MyBP-C specific antibodies.
TnI was predominantly monophosphorylated and total phosphorylation was 0.85 ± 0.03 molsPi/mol TnI. This phosphorylation level was significantly different (p < 0.0001) from both donor heart TnI (1.6 ± 0.06 molsPi/mol TnI) and HOCM heart TnI (0.19 ± 0.04 molsPi/mol TnI).
MyBP-C is phosphorylated at up to four sites.
In donor heart the 4P and 3P species predominate but in the pressure overload samples the 4P species was much reduced and 3P and 1P species predominated.
Total phosphorylation was 2.0 ± 0.2 molsPi/mol MyBP-C (n = 8) compared with 3.4 ± 0.07 (n = 21) in donor heart and 1.1 ± 0.1 (n = 10) in HOCM heart.
We conclude that pressure overload may be associated with substantial dephosphorylation of troponin I and MyBP-C. | 212,748,353 |
Title:
Decoding across sensory modalities reveals common supramodal signatures of conscious perception
Abstract:
Significance An outstanding goal in cognitive neuroscience is to understand the relationship between neurophysiological processes and conscious experiences.
More or less implicitly, it is assumed that common supramodal processes may underlie conscious perception in different sensory modalities.
We tested this idea directly using decoding analysis on brain activity following near-threshold stimulation, investigating common neural correlates of conscious perception between different sensory modalities.
Our results across all tested sensory modalities revealed the specific dynamic of a supramodal brain network interestingly including task-unrelated primary sensory cortices.
Our findings provide direct evidence of a common distributed activation pattern related to conscious access in different sensory modalities.
An increasing number of studies highlight common brain regions and processes in mediating conscious sensory experience.
While most studies have been performed in the visual modality, it is implicitly assumed that similar processes are involved in other sensory modalities.
However, the existence of supramodal neural processes related to conscious perception has not been convincingly shown so far.
Here, we aim to directly address this issue by investigating whether neural correlates of conscious perception in one modality can predict conscious perception in a different modality.
In two separate experiments, we presented participants with successive blocks of near-threshold tasks involving subjective reports of tactile, visual, or auditory stimuli during the same magnetoencephalography (MEG) acquisition.
Using decoding analysis in the poststimulus period between sensory modalities, our first experiment uncovered supramodal spatiotemporal neural activity patterns predicting conscious perception of the feeble stimulation.
Strikingly, these supramodal patterns included activity in primary sensory regions not directly relevant to the task (e.g., neural activity in visual cortex predicting conscious perception of auditory near-threshold stimulation).
We carefully replicate our results in a control experiment that furthermore show that the relevant patterns are independent of the type of report (i.e., whether conscious perception was reported by pressing or withholding a button press).
Using standard paradigms for probing neural correlates of conscious perception, our findings reveal a common signature of conscious access across sensory modalities and illustrate the temporally late and widespread broadcasting of neural representations, even into task-unrelated primary sensory processing regions. | 212,750,418 |
Title:
Transgenerational plasticity of inducible defences: Combined effects of grand‐parental, parental and current environments
Abstract:
Phenotypic plasticity can occur across generations (transgenerational plasticity) when environments experienced by the previous generations influenced offspring phenotype.
The evolutionary importance of transgenerational plasticity, especially regarding within-generational plasticity, is a currently hot topic in the plasticity framework.
How long an environmental effect can persist across generations and whether multigenerational effects are cumulative are primordial-for the evolutionary significance of transgenerational plasticity-but still unresolved questions.
In this study, we investigated how the grand-parental, parental and offspring exposures to predation cues shape the predator-induced defences of offspring in the Physa acuta snail.
We expected that the offspring phenotypes result from a three-way interaction among grand-parental, parental and offspring environments.
We exposed three generations of snails without and with predator cues according to a full factorial design and measured offspring inducible defences.
We found that both grand-parental and parental exposures to predator cues impacted offspring antipredator defences, but their effects were not cumulative and depended on the defences considered.
We also highlighted that the grand-parental environment did alter reaction norms of offspring shell thickness, demonstrating an interaction between the grand-parental transgenerational plasticity and the within-generational plasticity.
We concluded that the effects of multigenerational exposure to predator cues resulted on complex offspring phenotypic patterns which are difficult to relate to adaptive antipredator advantages. | 212,750,532 |
Title:
The Assessment of Overall Hangover Severity
Abstract:
The aim of this study was to critically evaluate and compare the different methods to assess overall hangover severity.
Currently, there are three multi-item hangover scales that are commonly used for this purpose.
All of them comprise a number of hangover symptoms for which an average score is calculated.
These scales were compared to a single, 1-item scale assessing overall hangover severity.
The results showed that the hangover symptom scales significantly underestimate (subjective) hangover severity, as assessed with a 1-item overall hangover severity scale.
A possible reason for this could be that overall hangover severity varies, depending on the frequency of occurrence of individual symptoms included in the respective scale.
In contrast, it can be assumed that, when completing a 1-item overall hangover scale, the rating includes all possible hangover symptoms and their impact on cognitive and physical functioning and mood, thus better reflecting the actually experienced hangover severity.
On the other hand, solely relying on hangover symptom scales may yield false positives in subjects who report not having a hangover.
When the average symptom score is greater than zero, this may lead to non-hungover subjects being categorized as having a hangover, as many of the somatic and psychological hangover symptoms may also be experienced without consuming alcohol (e.g., having a headache).
Taken together, the current analyses suggest that a 1-item overall hangover score is superior to hangover symptom scales in accurately assessing overall hangover severity.
We therefore recommend using a 1-item overall hangover rating as primary endpoint in future hangover studies that aim to assess overall hangover severity. | 212,750,644 |
Title:
Integration of Brain and Behavior Measures for Identification of Data-Driven Groups Cutting Across Children with ASD, ADHD, or OCD
Abstract:
Autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are clinically and biologically heterogeneous neurodevelopmental disorders (NDDs).
The objective of the present study was to integrate brain imaging and behavioral measures to identify new brain-behavior subgroups cutting across these disorders.
A subset of the data from the Province of Ontario Neurodevelopmental Disorder (POND) Network including participants with different NDDs (aged 6-16 years) that underwent cross-sectional T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scanning on the same 3T scanner, and behavioral/cognitive assessments was used.
Similarity Network Fusion was applied to integrate cortical thickness, subcortical volume, white matter fractional anisotropy (FA), and behavioral measures in 176 children with ASD, ADHD or OCD with complete data that passed quality control.
Normalized mutual information (NMI) was used to determine top contributing model features.
Bootstrapping, out-of-model outcome measures and supervised machine learning were each used to examine stability and evaluate the new groups.
Cortical thickness in socio-emotional and attention/executive networks and inattention symptoms comprised the top ten features driving participant similarity and differences between four transdiagnostic groups.
Subcortical volumes (pallidum, nucleus accumbens, thalamus) were also different among groups, although white matter FA showed limited differences.
Features driving participant similarity remained stable across resampling, and the new groups showed significantly different scores on everyday adaptive functioning.
Our findings open the possibility of studying new data-driven groups that represent children with NDDs more similar to each other than others within their own diagnostic group.
Such new groups can be evaluated longitudinally for prognostic utility and could be stratified for clinical trials targeted toward each group’s unique brain and behavioral profiles. | 212,790,591 |
Title:
Scabies: Application of the Novel Identify-Isolate-Inform Tool for Detection and Management
Abstract:
Scabies is a highly contagious, globally prevalent, parasitic skin infestation caused by Sarcoptes scabiei var.
hominis, also known as the itch mite.
There have been outbreaks not only in the developing world, but also in the developed world among refugees and asylum seekers.
Once infested with scabies mites, symptomatic patients, as well as asymptomatic carriers, quickly spread the disease through direct skin-to-skin contact.
Typically, symptoms of scabies are characterized by an erythematous, papular, pruritic rash associated with burrows.
Treatment of scabies involves using topical or systemic scabicides and treating secondary bacterial infections, if present.
Given the prevalence and contagiousness of scabies, measures to prevent its spread are essential.
Through application of the novel Identify-Isolate-Inform (3I) Tool, emergency medical providers can readily identify risk factors for exposure and important symptoms of the disease, thus limiting its spread through prompt scabicide therapy; isolate the patient until after treatment; and inform local public health authorities and hospital infection prevention, when appropriate.
Ultimately, these three actions can aid public health in controlling the transmission of scabies cases, thus ensuring the protection of the general public from this highly contagious skin infestation. | 212,812,865 |
Title:
Single cell epigenomic atlas of the developing human brain and organoids
Abstract:
Dynamic changes in chromatin accessibility coincide with important aspects of neuronal differentiation, such as fate specification and arealization and confer cell type-specific associations to neurodevelopmental disorders.
However, studies of the epigenomic landscape of the developing human brain have yet to be performed at single-cell resolution.
Here, we profiled chromatin accessibility of >75,000 cells from eight distinct areas of developing human forebrain using single cell ATAC-seq (scATACseq).
We identified thousands of loci that undergo extensive cell type-specific changes in accessibility during corticogenesis.
Chromatin state profiling also reveals novel distinctions between neural progenitor cells from different cortical areas not seen in transcriptomic profiles and suggests a role for retinoic acid signaling in cortical arealization.
Comparison of the cell type-specific chromatin landscape of cerebral organoids to primary developing cortex found that organoids establish broad cell type-specific enhancer accessibility patterns similar to the developing cortex, but lack many putative regulatory elements identified in homologous primary cell types.
Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development. | 212,819,403 |
Title:
Quantifying bias of COVID-19 prevalence and severity estimates in Wuhan, China that depend on reported cases in international travelers
Abstract:
Risk of COVID-19 infection in Wuhan has been estimated using imported case counts of international travelers, often under the assumption that all cases in travelers are ascertained.
Recent work indicates variation among countries in detection capacity for imported cases.
Singapore has historically had very strong epidemiological surveillance and contact-tracing capacity and has shown in the COVID-19 epidemic evidence of a high sensitivity of case detection.
We therefore used a Bayesian modeling approach to estimate the relative imported case detection capacity for other countries compared to that of Singapore.
We estimate that the global ability to detect imported cases is 38% (95% HPDI 22% - 64%) of Singapore′s capacity.
Equivalently, an estimate of 2.8 (95% HPDI 1.5 - 4.4) times the current number of imported cases, could have been detected, if all countries had had the same detection capacity as Singapore.
Using the second component of the Global Health Security index to stratify likely case-detection capacities, we found that the ability to detect imported cases relative to Singapore among high surveillance locations is 40% (95% HPDI 22% - 67%), among intermediate surveillance locations it is 37% (95% HPDI 18% - 68%), and among low surveillance locations it is 11% (95% HPDI 0% - 42%).
Using a simple mathematical model, we further find that treating all travelers as if they were residents (rather than accounting for the brief stay of some of these travelers in Wuhan) can modestly contribute to underestimation of prevalence as well.
We conclude that estimates of case counts in Wuhan based on assumptions of perfect detection in travelers may be underestimated by several fold, and severity correspondingly overestimated by several fold.
Undetected cases are likely in countries around the world, with greater risk in countries of low detection capacity and high connectivity to the epicenter of the outbreak. | 212,860,336 |
Title:
Machine intelligence design of 2019-nCoV drugs
Abstract:
Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020.
Currently, there is no effective treatment for this epidemic.
However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target.
Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%.
We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs.
Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC).
The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed. | 212,869,322 |
Title:
Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates
Abstract:
The induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection.
Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates.
In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses.
Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes.
Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies. | 212,901,263 |
Title:
Prefrontal state fluctuations control access to consciousness
Abstract:
In perceptual multistability, the content of consciousness alternates spontaneously between different interpretations of unchanged sensory input.
The source of these internally driven transitions in conscious perception is unknown.
Here we show that transient, low frequency (1-9 Hz) perisynaptic bursts in the macaque lateral prefrontal cortex precede spontaneous perceptual transitions in a no-report binocular motion rivalry task.
These low-frequency transients suppress 20-40 Hz oscillatory bursts that selectively synchronise the discharge activity of neuronal ensembles signalling conscious content.
Similar ongoing state changes, with dynamics resembling the temporal structure of spontaneous perceptual alternations during rivalry, dominate the prefrontal cortex during resting-state, thus pointing to their default, endogenous nature.
Our results suggest that prefrontal state fluctuations control access to consciousness through a reorganisation in the activity of feature-specific neuronal ensembles.
One sentence summary Prefrontal state transitions precede spontaneous transitions in the content of consciousness. | 213,003,653 |
Title:
A simple SIR model with a large set of asymptomatic infectives
Abstract:
There is increasing evidence that one of the most difficult problems in trying to control the ongoing COVID-19 epidemic is the presence of a large cohort of asymptomatic infectives.
We develop a SIR-type model taking into account the presence of asymptomatic, or however undetected, infective, and the substantially long time these spend being infective and not isolated.
In the second part of the note, we apply our model to the COVID-19 epidemics in Northern Italy, by numerical simulations based on estimate of certain parameters on the basisof medical evidence, and on fit of the other parameters from data on the first decade of March; the simulations reproduce quite satisfactorily the developements in the subsequent week, at difference with the standard SIR model.
Our simulations show that if no actions were taken, the estimates based on this model would be about one third of those based on the SIR model as far as the height of the epidemic peak is concerned, and about half for what concerns the time scale of the epidemics.
Moreover, the model suggests that an overwhelming part of the population would be in contact with the virus, most of them with no or very little symptoms.
We also consider the situation in which the restrictive measures are taken into account by a"reduction factor", and discuss on the one hand how a prompt isolation of asymptomatic infectives would change the dynamics in this framework, and on the other what the time-scale could be in this context; this both in the"mitigation"scenario, in which the measures taken only reduce the epidemic, and in the"eradication"one, in which the measures raise sufficiently the epidemc threshold, as it appears to have happened in China. | 213,003,944 |
Title:
Direct RNA sequencing reveals m6A modifications on adenovirus RNA are necessary for efficient splicing
Abstract:
Adenovirus is a nuclear replicating DNA virus reliant on host RNA processing machinery.
Processing and metabolism of cellular RNAs can be regulated by METTL3, which catalyzes the addition of N6-methyladenosine (m6A) to mRNAs.
While m6A-modified adenoviral RNAs have been previously detected, the location and function of this mark within the infectious cycle is unknown.
Since the complex adenovirus transcriptome includes overlapping spliced units that would impede accurate m6A mapping using short-read sequencing, we profiled m6A within the adenovirus transcriptome using a combination of meRIP-seq and direct RNA long-read sequencing to yield both nucleotide and transcript-resolved m6A detection.
Although both early and late viral transcripts contain m6A, depletion of m6A writer METTL3 specifically impacts viral late transcripts by reducing their splicing efficiency.
These data showcase a new technique for m6A discovery within individual transcripts at nucleotide resolution, and highlight the role of m6A in regulating splicing of a viral pathogen. | 213,007,747 |
Title:
A case of spontaneous subarachnoid hemorrhage and intraventricular hemorrhage with negative computed tomography angiography findings
Abstract:
Brain computed tomography angiography (CTA) is a useful tool for detecting subarachnoid hemorrhage (SAH) and cerebral aneurysms, but less reliably when cerebral aneurysms which are smaller than 2 mm.
We present a case of spontaneous SAH and intraventricular hemorrhage (IVH) with negative findings on brain CTA.
Due to the clinical presentation and positive neurologic examination, lumbar puncture was performed and xanthochromia of cerebrospinal fluid (CSF) had been noted.
Cerebral angiography was performed and showed a small unruptured saccular cerebral aneurysm (<2 mm). | 213,023,745 |
Title:
Human ESCRT-III Polymers Assemble on Positively Curved Membranes and Induce Helical Membrane Tube Formation
Abstract:
Endosomal sorting complexes required for transport-III (ESCRT-III) are thought to assemble in vivo inside membrane structures with a negative Gaussian curvature.
How membrane shape influences ESCRT-III polymerization and conversely how ESCRT-III polymers shape membranes is still unclear.
Here, we used human core ESCRT-III proteins, CHMP4B, CHMP2A, CHMP2B and CHMP3 to address this issue in vitro by combining membrane nanotube pulling experiments, cryo-electron microscopy, cryo-electron tomography and high-speed AFM.
We show that CHMP4B filaments bind preferentially to flat membranes or to membrane tubes with a positive mean curvature.
Both CHMP2B and CHMP2A/CHMP3 assemble on positively curved membrane tubes, the latter winding around the tubes.
Although combinations of CHMP4B/CHMP2B and CHMP4B/CHMP2A/CHMP3 are recruited to the neck of pulled membrane tubes, they also reshape large unilamellar vesicles into helical membrane tubes with a pipe surface shape.
Sub-tomogram averaging reveals that the filaments assemble parallel to the tube axis with some local perpendicular connections, highlighting the particular mechanical stresses imposed by ESCRT-III to stabilize the corkscrew-like membrane architecture.
Our results thus underline the versatile membrane remodeling activity of ESCRT-III that may be a general feature of ESCRT-III required for all or selected cellular membrane remodeling processes. | 213,043,635 |
Title:
Intra-Species Differences in Population Size shape Life History and Genome Evolution
Abstract:
The evolutionary forces shaping life history trait divergence within species are largely unknown.
Killifish (oviparous Cyprinodontiformes) evolved an annual life cycle as an exceptional adaptation to life in arid savannah environments characterized by seasonal water availability.
The turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate known to science and displays differences in lifespan among wild populations, representing an ideal natural experiment in the evolution and diversification of life history.
Here, by combining genome sequencing and population genetics, we investigate the evolutionary forces shaping lifespan among turquoise killifish populations.
We generate an improved reference assembly for the turquoise killifish genome, trace the evolutionary origin of the sex chromosome, and identify genes under strong positive and purifying selection, as well as those evolving neutrally.
We find that the shortest-lived turquoise killifish populations, which dwell in fragmented and isolated habitats at the outer margin of the geographical range of the species, are characterized by small effective population size and accumulate throughout the genome several small to large-effect deleterious mutations due to genetic drift.
The genes most affected by drift in the shortest-lived turquoise killifish populations are involved in the WNT signalling pathway, neurodegenerative disorders, cancer and the mTOR pathway.
As the populations under stronger genetic drift are the shortest-lived ones, we propose that limited population size due to habitat fragmentation and repeated population bottlenecks, by causing the genome-wide accumulation of deleterious mutations, cumulatively contribute to the short adult lifespan in turquoise killifish populations. | 213,067,333 |
Title:
Successful pregnancy and delivery achieved following intracytoplasmic sperm injection using teratozoospermic sperm exhibiting marked dysplasia of the fibrous sheath: a case report
Abstract:
A husband and his wife, both 34 years old, consulted our clinic because of primary infertility.
Sperm analysis revealed that the sperm concentration, motility, and progressive motility were (42.8±22.8)×10 6 /mL, 23.3%±12.2%, and 12.9%±6.1%, respectively.
Based on Krugar strict morphology criteria, 100% of the sperm were teratozoospermic, with 7.9% DNA fragmentation index.
Observation of the sperm under a transmission electron microscope revealed that most parts of the fibrous sheath (FS) surrounding the tails of the sperm were missing from midway through the principal piece to the end piece, although the sperm’s heads, necks and midpieces were morphologically normal.
To collect oocytes, the gonadotropin-releasing hormone antagonist protocol was carried out, and 7 oocytes were retrieved.
Intracytoplasmic sperm injection (ICSI) was performed for all the teratozoospermic sperm.
Of the 7 oocytes, 3 were fertilized, and one 8-cell embryo and 2 expanded blastocysts were vitrified.
Although repeated transfers of expanded blastocysts resulted in no implantation, one 8-cell embryo transfer in a hormone replacement therapy cycle led to pregnancy.
The pregnancy using an 8-cell vitrified embryo resulted in the delivery of a healthy female baby at 38 weeks of gestation.
No congenital malformations were found until 28 days after birth.
Our results demonstrated that healthy birth could be achieved following the transfer of an embryo derived from ICSI using teratozoospermic sperm exhibiting the dysplasia of the fibrous sheath (DFS).
Furthermore, while the previous reports on DFS have not investigated male infertility, we evaluated sperms from various aspects such as Kruger sperm function test, chromatin dispersion test, electron microscopy findings, time-lapse images of the obtained embryos, and concluded that ICSI could be desirable as a treatment policy for DFS. | 213,152,376 |
Title:
A database of freshwater fish species of the Amazon Basin
Abstract:
The Amazon Basin is an unquestionable biodiversity hotspot, containing the highest freshwater biodiversity on earth and facing off a recent increase in anthropogenic threats.
The current knowledge on the spatial distribution of the freshwater fish species is greatly deficient in this basin, preventing a comprehensive understanding of this hyper-diverse ecosystem as a whole.
Filling this gap was the priority of a transnational collaborative project, i.e. the AmazonFish project - https://www.amazon-fish.com/. Relying on the outputs of this project, we provide the most complete fish species distribution records covering the whole Amazon drainage.
The database, including 2,406 validated freshwater native fish species, 232,936 georeferenced records, results from an extensive survey of species distribution including 590 different sources (e.g. published articles, grey literature, online biodiversity databases and scientific collections from museums and universities worldwide) and field expeditions conducted during the project.
This database, delivered at both georeferenced localities (21,500 localities) and sub-drainages grains (144 units), represents a highly valuable source of information for further studies on freshwater fish biodiversity, biogeography and conservation. | 213,162,605 |
Title:
Complications after operatively treated distal radius fractures
Abstract:
In the recent years, treatment of distal radius fractures (DRF) has advanced considerably.
Surgical fixation with palmar angular stable plate has gained popularity, due to a reported lower complication rate when compared to dorsal fixation.
The type of trauma or injury, surgical procedure and impaired bone quality are all contributors to complications in DRF.
The main aim of this review is to summarize the most common complications and possible therapeutic solutions.
In addition, strategies for minimizing these complications will be discussed. | 213,169,812 |
Title:
Multidisciplinary database of permeability of fault zones and surrounding protolith rocks at world-wide sites
Abstract:
Brittle faults and fault zones are important fluid flow conduits through the upper part of Earth’s crust that are involved in many well-known phenomena (e.g. earthquakes, thermal water and gas transport, or water leakage to underground tunnels).
The permeability property, or the ability of porous materials to conduct water and gas, is one of the key parameters required in understanding and predicting fluid flow.
Although close to a thousand studies have been done, and permeability tested in parts of fault zones, a sytematic summary and database is lacking.
This data descriptor is for a multi-disciplinary world-wide compilation and review of bulk and matrix permeability of fault zones: 410 datasets, 521 reviewed sites, 379 locations, >10000 publications searched.
The review covers studies of faulting processes, geothermal engineering, radioactive waste repositories, groundwater resources, petroleum reservoirs, and underground engineering projects.
The objectives are to stimulate the cross-disciplinary data sharing and communication about fault zone hydrogeology, document the biases and strategies for testing of fault zones, and provide the basic statistics of permeability values for models that require these parameters.
Measurement(s) permeability Technology Type(s) digital curation Factor Type(s) data source • geographic location Sample Characteristic - Environment geological fault Measurement(s) permeability Technology Type(s) digital curation Factor Type(s) data source • geographic location Sample Characteristic - Environment geological fault Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.11933391 | 213,175,348 |
Title:
Bi-stability of SUDR+K model of epidemics and test kits applied to COVID-19
Abstract:
Motivated with various responses of world governments to COVID-19, here we develop a toy model of the dependence epidemics spreading on the availability of tests for disease.
Our model, that we call SUDR+K, is based on usual SIR model, but it splits the total fraction of infected individuals into two components: those that are undetected and those that are detected through tests.
Moreover, we assume that available tests increase at a constant rate from the beginning of epidemics but are consumed to detect infected individuals.
Strikingly we find a bi-stable behavior between a phase with a giant fraction of infected and a phase with a very small fraction.
We show that the separation between these two regimes is governed by a match between the rate of testing and a rate of infection spread at given time.
We also show that the existence of two phases does not depend on the mathematical choice of the form of the term describing the rate at which undetected individuals are tested and detected.
Presented research implies that a vigorous early testing activity, before the epidemics enters into its giant phase, can potentially keep epidemics under control, and that even a very small change in rate of testing can increase or decrease the size of the whole epidemics of various orders of magnitude.
For the real application of realistic model to ongoing epidemics, we would gladly collaborate with field epidemiologists in order to develop quantitative models of testing process. | 213,175,522 |
Title:
Serial Interval of COVID-19 among Publicly Reported Confirmed Cases
Abstract:
We estimate the distribution of serial intervals for 468 confirmed cases of 2019 novel coronavirus disease reported in China as of February 8, 2020.
The mean interval was 3.96 days (95% CI 3.53-4.39 days), SD 4.75 days (95% CI 4.46-5.07 days); 12.6% of case reports indicated presymptomatic transmission. | 213,186,717 |
Title:
Prognostic impact of D2-plus lymphadenectomy and optimal extent of lymphadenectomy in advanced gastric antral carcinoma: Propensity score matching analysis
Abstract:
Objective ::: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior (No. 8p, No. 12b/p, No. 13, and No. 14v), and para-aortic (No. 16a2, and No. 16b1) lymph nodes (LNs) in subtotal gastrectomy for advanced gastric antral carcinoma. ::: ::: ::: Methods ::: A total of 203 patients with advanced gastric cancer (GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.
Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses.
The therapeutic value index (TVI) was calculate to evaluate the survival benefit of dissecting each LN station.
::: ::: ::: Results ::: Of 102 patients with D2-plus lymphadenectomy, 21 (20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy.
After matching, the overall survival (OS) was significantly better in the D2-plus than the D2 group (P=0.030).
In the multivariate survival analysis, D2-plus lymphadenectomy (hazard ratio, 0.516; P=0.006) was confirmed to significantly improve the survival rate.
In the logistic regression analysis, pN stage [odds ratio (OR), 2.533; 95% confidence interval (95% CI), 1.368-4.691; P=0.003] and extent of LNs metastasis (OR, 5.965; 95% CI, 1.335-26.650; P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy.
The TVI of patient with metastasis to LNs station was 7.1 (No. 8p), 5.7 (No. 12p), 5.1 (No. 13), and 7.1 (both No. 16a2 and No. 16b1), respectively. ::: ::: ::: Conclusions ::: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16. | 213,192,553 |
Title:
Surfactant-enhanced DNA accessibility to nuclease accelerates phenotypic β-lactam antibiotic susceptibility testing of Neisseria gonorrhoeae
Abstract:
Rapid antibiotic susceptibility testing (AST) for Neisseria gonorrhoeae (Ng) is critically needed to counter widespread antibiotic resistance.
Detection of nucleic acids in genotypic AST can be rapid, but it has not been successful for β-lactams (the largest antibiotic class used to treat Ng).
Rapid phenotypic AST for Ng is challenged by the pathogen's slow doubling time and the lack of methods to quickly quantify the pathogen's response to β-lactams.
Here, we asked two questions: (1) Is it possible to use nucleic acid quantification to measure the β-lactam susceptibility phenotype of Ng very rapidly, using antibiotic-exposure times much shorter than the 1- to 2-h doubling time of Ng? (2) Would such short-term antibiotic exposures predict the antibiotic resistance profile of Ng measured by plate growth assays over multiple days?
To answer these questions, we devised an innovative approach for performing a rapid phenotypic AST that measures DNA accessibility to exogenous nucleases after exposure to β-lactams (termed nuclease-accessibility AST [nuc-aAST]).
We showed that DNA in antibiotic-susceptible cells has increased accessibility upon exposure to β-lactams and that a judiciously chosen surfactant permeabilized the outer membrane and enhanced this effect.
We tested penicillin, cefixime, and ceftriaxone and found good agreement between the results of the nuc-aAST after 15-30 min of antibiotic exposure and the results of the gold-standard culture-based AST measured over days.
These results provide a new pathway toward developing a critically needed phenotypic AST for Ng and additional global-health threats. | 213,192,892 |
Title:
Health security capacities in the context of COVID-19 outbreak: an analysis of International Health Regulations annual report data from 182 countries
Abstract:
BACKGROUND: Public health measures to prevent, detect, and respond to events are essential to control public health risks, including infectious disease outbreaks, as highlighted in the International Health Regulations (IHR).
In light of the outbreak of 2019 novel coronavirus disease (COVID-19), we aimed to review existing health security capacities against public health risks and events.
METHODS: We used 18 indicators from the IHR State Party Annual Reporting (SPAR) tool and associated data from national SPAR reports to develop five indices: (1) prevent, (2) detect, (3) respond, (4) enabling function, and (5) operational readiness.
We used SPAR 2018 data for all of the indicators and categorised countries into five levels across the indices, in which level 1 indicated the lowest level of national capacity and level 5 the highest.
We also analysed data at the regional level (using the six geographical WHO regions).
FINDINGS: Of 182 countries, 52 (28%) had prevent capacities at levels 1 or 2, and 60 (33%) had response capacities at levels 1 or 2.
81 (45%) countries had prevent capacities and 78 (43%) had response capacities at levels 4 or 5, indicating that these countries were operationally ready.
138 (76%) countries scored more highly in the detect index than in the other indices.
44 (24%) countries did not have an effective enabling function for public health risks and events, including infectious disease outbreaks (7 [4%] at level 1 and 37 [20%] at level 2).
102 (56%) countries had level 4 or level 5 enabling function capacities in place.
32 (18%) countries had low readiness (2 [1%] at level 1 and 30 [17%] at level 2), and 104 (57%) countries were operationally ready to prevent, detect, and control an outbreak of a novel infectious disease (66 [36%] at level 4 and 38 [21%] at level 5).
INTERPRETATION: Countries vary widely in terms of their capacity to prevent, detect, and respond to outbreaks.
Half of all countries analysed have strong operational readiness capacities in place, which suggests that an effective response to potential health emergencies could be enabled, including to COVID-19.
Findings from local risk assessments are needed to fully understand national readiness capacities in relation to COVID-19.
Capacity building and collaboration between countries are needed to strengthen global readiness for outbreak control.
FUNDING: None. | 213,194,380 |
Title:
Mining Archive.org’s Twitter Stream Grab for Pharmacovigilance Research Gold
Abstract:
In the last few years Twitter has become an important resource for the identification of Adverse Drug Reactions (ADRs), monitoring flu trends, and other pharmacovigilance and general research applications.
Most researchers spend their time crawling Twitter, buying expensive pre-mined datasets, or tediously and slowly building datasets using the limited Twitter API.
However, there are a large number of datasets that are publicly available to researchers which are underutilized or unused.
In this work, we demonstrate how we mined over 9.4 billion Tweets from archive.org’s Twitter stream grab using a drug-term dictionary and plenty of computing power.
Knowing that not everything that shines is gold, we used pre-existing drug-related datasets to build machine learning models to filter our findings for relevance.
In this work we present our methodology and the 3,346,758 identified tweets for public use in future research. | 213,227,515 |
Title:
LRRK2 mutation alters behavioral, synaptic and non-synaptic adaptations to acute social stress
Abstract:
Parkinson’s disease (PD) risk is increased by stress and certain gene mutations, including the most prevalent PD-linked mutation LRRK2-G2019S.
Both PD and stress increase risk for psychiatric symptoms, yet it is unclear how PD-risk genes alter neural circuitry in response to stress that may promote psychopathology.
Here we show significant differences between adult G2019S knockin and wildtype (wt) mice in stress-induced behaviors, with an unexpected uncoupling of depression-like and hedonic-like responses in G2019S mice.
Moreover, mutant spiny projection neurons in nucleus accumbens (NAc) lack an adaptive, stress-induced change in excitability displayed by wt neurons, and instead show stress-induced changes in synaptic properties that wt neurons lack.
Some synaptic alterations in NAc are already evident early in postnatal life.
Thus, G2019S alters the magnitude and direction of behavioral responses to stress that may reflect unique modifications of adaptive plasticity in cells and circuits implicated in psychopathology in humans. | 213,261,076 |
Title:
Dancing bees evaluate agricultural forage resources as inferior to central urban land
Abstract:
Recent evidence suggests that flower-rich areas within cities could play an important role in pollinator conservation, but direct comparison of agricultural and urban areas has proved challenging to perform over large scales.
Here we use the waggle dances of honeybees (Apis mellifera L.) to evaluate floral resource availability over the entire season at deeply urban or agricultural sites.
Through analysis of 3378 dances that were performed over two years by 20 colonies in SE England, we show that foraging trip distance is consistently lower at urban sites across the entire season, implying a higher availability of forage in heavily urbanized areas.
Urban bees also collected nectar with a higher mean sugar content.
From the self-reported perspective of a generalist pollinator, the modern agricultural landscapes that we studied provided insufficient and transient resources relative to heavily urbanised areas, which may represent important refuges within an impoverished landscape. | 213,271,671 |
Title:
A head-fixation system for continuous monitoring of force generated during behavior
Abstract:
Many studies in neuroscience use head-fixed behavioral preparations, which confer a number of advantages, including the ability to limit the behavioral repertoire and use techniques for large-scale monitoring of neural activity.
But traditional studies using this approach use extremely limited behavioral measures, in part because it is difficult to detect the subtle movements and postural adjustments that animals naturally exhibit during head fixation.
Here we report the development of an apparatus that is equipped with analog load cells capable of precisely monitoring the continuous forces exerted by mice.
The load cells reveal the dynamic nature of movements generated not only around the time of task-relevant events, such as the regular presentation of stimuli and rewards, but also during periods of no apparent overt behavior that occur outside of the experimenter-defined events.
It generates a new and rich set of behavioral measures that have been neglected in previous experiments.
We detail the construction of the system, which can be 3D-printed and assembled at low cost (∼$140), show behavioral results collected from head-fixed mice, and demonstrate that neural activity can be highly correlated with the subtle, whole-body movements continuously produced during head restraint. | 213,282,829 |
Title:
Genetic predictors of participation in optional components of UK Biobank
Abstract:
Large studies (e.g. UK Biobank) are increasingly used for GWAS and Mendelian randomization (MR) studies.
Selection into and dropout from studies may bias genetic and phenotypic associations.
We examine genetic factors affecting participation in four optional components in up to 451,306 UK Biobank participants.
We used GWAS to identify genetic variants associated with participation, MR to estimate effects of phenotypes on participation, and genetic correlations to compare participation bias across different studies.
32 variants were associated with participation in one of the optional components (P<6×10-9), including loci with known links to intelligence and Alzheimer’s disease.
Genetic correlations demonstrated that participation bias was common across studies.
MR showed that longer educational duration, older menarche and taller stature increased participation, whilst higher levels of adiposity, dyslipidaemia, neuroticism, Alzheimer’s and schizophrenia reduced participation.
Our effect estimates can be used for sensitivity analysis to account for selective participation biases in genetic or non-genetic analyses. | 213,285,257 |
Title:
Genome-wide transcriptomics identifies an early preclinical signature of prion infection
Abstract:
The clinical course of prion diseases is accurately predictable despite long latency periods, suggesting that prion pathogenesis is driven by precisely timed molecular events.
We constructed a searchable genome-wide atlas of mRNA abundance, splicing and editing alterations during the course of disease in prion-inoculated mice.
Prion infection induced transient changes in mRNA abundance and processing already at eight weeks post inoculation, well ahead of any neuropathological and clinical signs.
In contrast, microglia-enriched genes displayed an increase simultaneous with the appearance of clinical symptoms, whereas neuronal-enriched transcripts remained unchanged until the very terminal stage of disease.
This suggests that glial pathophysiology, rather than neuronal demise, represents the final driver of disease.
The administration of young plasma attenuated the occurrence of early mRNA abundance alterations and delayed symptoms in the terminal phase of the disease.
The early onset of prion-induced molecular changes might thus point to novel biomarkers and potential interventional targets. | 213,295,297 |
Title:
Assessing the performance of index calibration survey methods to monitor populations of wide‐ranging low‐density carnivores
Abstract:
Apex carnivores are wide-ranging, low-density, hard to detect, and declining throughout most of their range, making population monitoring both critical and challenging.
Rapid and inexpensive index calibration survey (ICS) methods have been developed to monitor large African carnivores.
ICS methods assume constant detection probability and a predictable relationship between the index and the actual population of interest.
The precision and utility of the resulting estimates from ICS methods have been questioned.
We assessed the performance of one ICS method for large carnivores-track counts-with data from two long-term studies of African lion populations.
We conducted Monte Carlo simulation of intersections between transects (road segments) and lion movement paths (from GPS collar data) at varying survey intensities.
Then, using the track count method we estimated population size and its confidence limits.
We found that estimates either overstate precision or are too imprecise to be meaningful.
Overstated precision stemmed from discarding the variance from population estimates when developing the method and from treating the conversion from tracks counts to population density as a back-transformation, rather than applying the equation for the variance of a linear function.
To effectively assess the status of species, the IUCN has set guidelines, and these should be integrated in survey designs.
We propose reporting the half relative confidence interval width (HRCIW) as an easily calculable and interpretable measure of precision.
We show that track counts do not adhere to IUCN criteria, and we argue that ICS methods for wide-ranging low-density species are unlikely to meet those criteria.
Established, intensive methods lead to precise estimates, but some new approaches, like short, intensive, (spatial) capture-mark-recapture (CMR/SECR) studies, aided by camera trapping and/or genetic identification of individuals, hold promise.
A handbook of best practices in monitoring populations of apex carnivores is strongly recommended. | 213,325,434 |
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