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Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people

BACKGROUND: Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. METHODS AND FINDINGS: We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%–27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. CONCLUSIONS: Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.

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Pulmonary fibrosis and its related factors in discharged patients with new coronavirus pneumonia: A cohort study

Background: Thousands of the Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals, persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis. Methods: : This study involves 462 laboratory confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 days to 150 days after the onset of the disease, and lung function tests were conducted in about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established. Results: : Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of COVID-19 patients revealed abnormal condition in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups. Conclusions: : Persistent pulmonary fibrosis was more likely to develop in patients with older age, high BMI, severe/critical condition, fever, long time to turn the viral RNA negative, pre-existing disease and delay to admission. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average Area Under the Curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

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Communicating health crisis: a content analysis of global media framing of COVID-19.

Background: This study examines the global media framing of coronavirus disease 2019(COVID-19) to understand the dominant frames and how choice of words compares in the media. Periods of health crisis such as the outbreak of coronavirus pandemic add to the enormous burden of the media in keeping people constantly informed. Extant literature suggests that when a message is released through the media, what matters most is not what is said but how it is said. As such, the media could either mitigate or accentuate the crisis depending on the major frames adopted for the coverage. Methods: The study utilises content analysis. Data were sourced from LexisNexis database and two websites that yielded 6145 items used for the analysis. Nine predetermined frames were used for the coding. Results: Human Interest and fear/scaremongering frames dominated the global media coverage of the pandemic. We align our finding with the constructionist frame perspective which assumes that the media as information processor creates 'interpretative packages' in order to both reflect and add to the 'issue culture' because frames that paradigmatically dominate event coverage also dominate audience response. The language of the coverage of COVID-19 combines gloom, hope, precaution and frustration at varied proportions. Conclusion: We conclude that global media coverage of COVID-19 was high, but the framing lacks coherence and sufficient self-efficacy and this can be associated with media's obsession for breaking news. The preponderance of these frames not only shapes public perception and attitudes towards the pandemic but also risks causing more problems for those with existing health conditions due to fear or panic attack.

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Factors driving availability of COVID-19 convalescent plasma: Insights from a demand, production, and supply model

BACKGROUND: COVID-19 Convalescent Plasma (CCP) is a promising treatment for COVID-19. Blood collectors have rapidly scaled up collection and distribution programs. METHODS: We developed a detailed simulation model of CCP donor recruitment, collection, production, and distribution processes. We ran our model using varying epidemic trajectories from 11 U.S. states and with key input parameters drawn from wide ranges of plausible values to identify key drivers of ability to scale collections capacity and meet demand for CCP. RESULTS: Utilization of available CCP collections capacity followed increases in COVID-19 hospital discharges with a lag. Utilization never exceeded 75% of available capacity in most simulations. Demand was met for most of the simulation period in most simulations, but a substantial portion of demand went unmet during early, sharp increases in hospitalizations. For epidemic trajectories that included multiple epidemic peaks, second wave demand could generally be met due to stockpiles established during the decline from an earlier peak. Apheresis machine capacity (number of machines) and probability that COVID-19 recovered individuals are willing to donate were the most important supply-side drivers of ability to meet demand. Recruitment capacity was important in states with early peaks. CONCLUSIONS: Epidemic trajectory was the most important determinant of ability to meet demand for CCP, although our simulations revealed several contributing operational drivers of CCP program success.

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Geographical Variations in Host Predisposition to COVID-19 Related Anosmia, Ageusia, and Neurological Syndromes

The novel coronavirus disease (COVID-19), has become the most critical global health challenge in recent history. With SARS-CoV-2 infection, there was an unexpectedly high and specific prevalence of olfactory and taste disorders (OTDs). These high rates of hyposmia and hypogeusia, initially reported as up to 89% in European case series, led to the global inclusion of loss of taste and/or smell as a distinctive feature of COVID-19. However, there is emerging evidence that there are striking differences in the rates of OTDs in East Asian countries where the disease first emerged, as compared to Western countries (15.8 vs. 60.9%, p-value < 0.01). This may be driven by either variations in SARS-CoV-2 subtypes presenting to different global populations or genotypic differences in hosts which alter the predisposition of these different populations to the neuroinvasiveness of SARS-CoV-2. We also found that rates of OTDs were significantly higher in objective testing for OTDs as compared to subjective testing (73.6 vs. 60.8%, p-value = 0.03), which is the methodology employed by most studies. Concurrently, it has also become evident that racial minorities across geographically disparate world populations suffer from disproportionately higher rates of COVID-19 infection and mortality. In this mini review, we aim to delineate and explore the varying rates of olfactory and taste disorders amongst COVID-19 patients, by focusing on their underlying geographical, testing, ethnic and socioeconomic differences. We examine the current literature for evidence of differences in the olfactory and gustatory manifestations of COVID-19 and discuss current pathophysiological hypotheses for such differences.

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New dynamical behaviour of the coronavirus (2019-ncov) infection system with non-local operator from reservoirs to people

The mathematical accepts while analysing the evolution of real word problems magnetizes the attention of many scholars In this connection, we analysed and find the solution for nonlinear system exemplifying the most dangerous and deadly virus called coronavirus The six ordinary differential equations of fractional order nurtured the projected mathematical model and they are analysed using q-homotopy analysis transform method (q-HATM) Further, most considered fractional operator is applied to study and capture the more corresponding consequences of the system, known as Caputo operator For different fractional order, the natures of the achieved results are illustrated in plots Lastly, the present investigation may aid us analyse the distinct and diverse classes of models exemplifying real-world problems and helps to envisage their corresponding nature with parameters associated with the models © 2021 NSP Natural Sciences Publishing Cor

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Effectiveness of the ChAdOx1 vaccine in the elderly during SARS-CoV-2 Gamma variant transmission in Brazil

BackgroundA two-dose regimen of ChAdOx1 coronavirus disease 19 (Covid-19) vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of severe acute respiratory syndrome 2 (SARS-CoV-2). MethodsWe conducted a test-negative case-control study to estimate the effectiveness of ChAdOx1 vaccine in adults aged 60 years or older during a Gamma-variant-associated epidemic in Sao Paulo state, Brazil, between 17 January and 2 July 2021. Cases and matched test-negative controls were individuals, identified from surveillance databases, who experienced an acute respiratory illness and underwent SARS-CoV-2 RT-PCR testing. We used conditional logistic regression to estimate the effectiveness by dose against RT-PCR-confirmed Covid-19, Covid-19 hospitalization, and Covid-19-related death. Results61,164 individuals were selected into matched case-control pairs. Starting [≥]28 days after the first dose, adjusted effectiveness of a single dose of ChAdOx1 was 33.4% (95% CI, 26.4 to 39.7) against Covid-19, 55.1% (95% CI, 46.6 to 62.2) against hospitalization, and 61.8% (95% CI, 48.9 to 71.4) against death. Starting [≥]14 days after the second dose, the adjusted effectiveness of the two-dose schedule was 77.9% (95% CI, 69.2 to 84.2) against Covid-19, 87.6% (95% CI, 78.2 to 92.9) against hospitalization, and 93.6% (95% CI, 81.9 to 97.7) against death. ConclusionsCompletion of the ChAdOx1 vaccine schedule afforded significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant transmission.

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Predictors of mortality among long-term care residents with SARS-CoV-2 infection

Background: While individuals living in long-term care (LTC) homes have experienced adverse outcomes of SARS-CoV-2 infection, few studies have examined a broad range of predictors of 30-day mortality in this population. Methods: We studied residents living in LTC homes in Ontario, Canada, who underwent PCR testing for SARS-CoV-2 infection from January 1 to August 31, 2020, and examined predictors of all-cause death within 30 days after a positive test for SARS-CoV-2. We examined a broad range of risk factor categories including demographics, comorbidities, functional status, laboratory tests, and characteristics of the LTC facility and surrounding community were examined. In total, 304 potential predictors were evaluated for their association with mortality using machine learning (Random Forest). Results: A total of 64,733 residents of LTC, median age 86 (78, 91) years (31.8% men), underwent SARS-CoV-2 testing, of whom 5029 (7.8%) tested positive. Thirty-day mortality rates were 28.7% (1442 deaths) after a positive test. Of 59,702 residents who tested negative, 2652 (4.4%) died within 30 days of testing. Predictors of mortality after SARS-CoV-2 infection included age, functional status (e.g., activity of daily living score and pressure ulcer risk), male sex, undernutrition, dehydration risk, prior hospital contacts for respiratory illness, and duration of comorbidities (e.g., heart failure, COPD). Lower GFR, hemoglobin concentration, lymphocyte count, and serum albumin were associated with higher mortality. After combining all covariates to generate a risk index, mortality rate in the highest risk quartile was 48.3% compared with 7% in the first quartile (odds ratio 12.42, 95%CI: 6.67, 22.80, p < 0.001). Deaths continued to increase rapidly for 15 days after the positive test. Conclusions: LTC residents, particularly those with reduced functional status, comorbidities, and abnormalities on routine laboratory tests, are at high risk for mortality after SARS-CoV-2 infection. Recognizing high-risk residents in LTC may enhance institution of appropriate preventative measures. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

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Interleukin-6: obstacles to targeting a complex cytokine in critical illness

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is crucial for the correct interpretation of IL-6 concentrations in the blood or lung, the use of IL-6 as a critical care biomarker, or the design of effective anti-IL-6 strategies. Here, we outline the role of IL-6 in health and disease, explain the different types of IL-6 signalling and their contribution to the net biological effect of the cytokine, describe the approaches to IL-6 inhibition that are currently available, and discuss implications for the future use of treatments such as tocilizumab in the critical care setting.

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Construction and numerical analysis of a fuzzy non-standard computational method for the solution of an SEIQR model of COVID-19 dynamics

This current work presents an SEIQR model with fuzzy parameters. The use of fuzzy theory helps us to solve the problems of quantifying uncertainty in the mathematical modeling of diseases. The fuzzy reproduction number and fuzzy equilibrium points have been derived focusing on a model in a specific group of people having a triangular membership function. Moreover, a fuzzy non-standard finite difference (FNSFD) method for the model is developed. The stability of the proposed method is discussed in a fuzzy sense. A numerical verification for the proposed model is presented. The developed FNSFD scheme is a reliable method and preserves all the essential features of a continuous dynamical system.

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Mobile Health to Improve Adherence and Patient Experience in Heart Transplantation Recipients: The mHeart Trial

Non-adherence after heart transplantation (HTx) is a significant problem. The main objective of this study was to evaluate if a mHealth strategy is more effective than standard care in improving adherence and patients’ experience in heart transplant recipients. Methods: This was a single-center, randomized controlled trial (RCT) in adult recipients >1.5 years post-HTx. Participants were randomized to standard care (control group) or to the mHeart Strategy (intervention group). For patients randomized to the mHeart strategy, multifaceted theory-based interventions were provided during the study period to optimize therapy management using the mHeart mobile application. Patient experience regarding their medication regimens were evaluated in a face-to-face interview. Medication adherence was assessed by performing self-reported questionnaires. A composite adherence score that included the SMAQ questionnaire, the coefficient of variation of drug levels and missing visits was also reported. Results: A total of 134 HTx recipients were randomized (intervention N = 71; control N = 63). Mean follow-up was 1.6 (SD 0.6) years. Improvement in adherence from baseline was significantly higher in the intervention group versus the control group according to the SMAQ questionnaire (85% vs. 46%, OR = 6.7 (2.9; 15.8), p-value < 0.001) and the composite score (51% vs. 23%, OR = 0.3 (0.1; 0.6), p-value = 0.001). Patients’ experiences with their drug therapy including knowledge of their medication timing intakes (p-value = 0.019) and the drug indications or uses that they remembered (p-value = 0.003) significantly improved in the intervention versus the control group. Conclusions: In our study, the mHealth-based strategy significantly improved adherence and patient beliefs regarding their medication regimens among the HTx population. The mHeart mobile application was used as a feasible tool for providing long-term, tailor-made interventions to HTx recipients to improve the goals assessed.

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Carbon dots for virus detection and therapy

Recent experience with the COVID-19 pandemic should be a lesson learnt with respect to the effort we have to invest in the development of new strategies for the treatment of viral diseases, along with their cheap, easy, sensitive, and selective detection. Since we live in a globalized world where just hours can play a crucial role in the spread of a virus, its detection must be as quick as possible. Thanks to their chemical stability, photostability, and superior biocompatibility, carbon dots are a kind of nanomaterial showing great potential in both the detection of various virus strains and a broad-spectrum antiviral therapy. The biosensing and antiviral properties of carbon dots can be tuned by the selection of synthesis precursors as well as by easy post-synthetic functionalization. In this review, we will first summarize current options of virus detection utilizing carbon dots by either electrochemical or optical biosensing approaches. Secondly, we will cover and share the up-to-date knowledge of carbon dots’ antiviral properties, which showed promising activity against various types of viruses including SARS-CoV-2. The mechanisms of their antiviral actions will be further adressed as well. Finally, we will discuss the advantages and distadvantages of the use of carbon dots in the tangled battle against viral infections in order to provide valuable informations for further research and development of new virus biosensors and antiviral therapeutics. [Image: see text]

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Agent’s Optimal Compensation Under Inflation Risk by Using Dynamic Contract Model

This paper studies the problem of principal-agent with moral hazard in continuous time. The firm’s cash flow is described by geometric Brownian motion (hereafter GBM). The agent affects the drift of the firm’s cash flow by her hidden effort. Meanwhile, the firm rewards the agent with corresponding compensation and equity which depend on the output. The model extends dynamic optimal contract theory to an inflation environment. Firstly, the authors obtain the dynamic equation of the firm’s real cash flow under inflation by using the Itô formula. Then, the authors use the martingale representation theorem to obtain agent’s continuation value process. Moreover, the authors derive the Hamilton-Jacobi-Bellman (HJB) equation of investor’s value process, from which the authors derive the investors’ scaled value function by solving the second-order ordinary differential equation. Comparing with He([1]), the authors find that inflation risk affects the agent’s optimal compensation depending on the firm’s position in the market.

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The Role of Media Sources for COVID-19 Information on Engaging in Recommended Preventive Behaviors among Medicare Beneficiaries Aged ≥ 65 Years

OBJECTIVES: The public relies on various media sources and communication platforms for receipt of COVID-19 information. Therefore, identifying the primary sources of COVID-19 information among older adults can be valuable, as it can enable information on life-saving measures to be effectively disseminated to this population. METHODS: We analyzed the Medicare Current Beneficiary Survey COVID-19 Supplement that was administrated from June 2020 through July 2020 (n=8,050). A survey-weighted logistic model was conducted to examine the association between sources of COVID-19 information Medicare beneficiaries most relied on (i.e., traditional news sources, social media, comments/guidance from government officials, other webpages/internet, friends/family members, and health care providers) and engaging in all three recommended preventive behaviors (i.e., mask wearing, social distancing, and handwashing). RESULTS: Among study participants, 89.8% engaged in all three recommended preventive behaviors. Approximately 59.3% of beneficiaries reported that they most relied upon traditional news sources for COVID-19 information; 11.4% reported health care providers; 10.6% reported comments/guidance from government officials; 8.8% reported other webpages/internet, 8.6% reported friends/family members; and 1.3% reported they relied upon social media. Beneficiaries who relied on comments/guidance from government officials for COVID-19 information (vs. traditional news sources) were more likely to engage in preventive behaviors (OR=1.68, 95% CI=1.20,2.35). However, those who relied on COVID-19 information from friends/family members (vs. traditional news sources) were less likely to engage in preventive behaviors (OR=0.56, 95% CI=0.44,0.73). DISCUSSION: Our findings can inform decision making about the effective communication sources to reach Medicare beneficiaries for public health messaging regarding preventive measures, including COVID-19 vaccination.

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Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: A Systematic Review and Meta-Analysis

BACKGROUND: Currently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma. OBJECTIVE: To compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma. METHODS: This systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138). RESULTS: A quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)]. LIMITATIONS: A relatively small number of articles were eligible and there was considerable heterogeneity across the included studies. CONCLUSIONS: Serum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).

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Application and Prospect of a Mobile Hospital in Disaster Response

Disasters such as an earthquake, a flood, and an epidemic usually lead to large numbers of casualties accompanied by disruption of the functioning of local medical institutions. A rapid response of medical assistance and support is required. Mobile hospitals have been deployed by national and international organizations at disaster situations in the past decades, which play an important role in saving casualties and alleviating the shortage of medical resources. In this paper, we briefly introduce the types and characteristics of mobile hospitals used by medical teams in disaster rescue, including the aspects of structural form, organizational form, and mobile transportation. We also review the practices of mobile hospitals in disaster response and summarize the problems and needs of mobile hospitals in disaster rescue. Finally, we propose the development direction of mobile hospitals, especially on the development of intelligence, rapid deployment capabilities, and modularization, which provide suggestions for further research and development of mobile hospitals in the future.

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Secondary bacterial co-infection and mortality risk in intubated patients with critically ill COVID19

Background:Secondary bacterial co-infections are not common in patients with COVID19.However ,the rate of bacterial pneumonia is high in critically ill patients with COVID19 and there is increased risk of joining bacterial infection by increasing of severity of COVID19 and achieving maximal rate in intubated patients.And there is increased rate of overuse of broad-spectrum antibiotics in patients admitted to the intensive care unit(ICU) department.Objective:The aim of our investigation was to evaluate the rate of secondary bacterial co-infection in critically ill patients with COVID19 and its impact to the mortality rate in such patients.Method and measurements:Of 129 COVID-19 patients admitted in our ICU from 21 April 2020 to 15 August 2020,93 have been mechanically ventilated.BALF was performed in 68 patients during ICU stay and all were suspected of bacterial pneumonia.Bacterial cultures of BALF positively defined in case of grew with significant amount of bacteria(ie,&gt;-104 colony-forming units/ml).All pneumonia cases in intubated patients was assessed as Ventilator-associated pneumonia(VAP) and was defined as eraly-onset and late onset as pneumonia diagnosed before and after 5 days of mechanical ventilation, respectively.Results:In 51% (n=35) of 78 patients was obtained bacterial cultires and just in 5(7.4%) of 68 patients was evaluated the early-onset VAP and in remaining 63 patients (92%) of patients was detected late-onset VAP.VAP in patients commonly was associated with ARDS compared to non-VAP patients(OR 3.57[0.89-7.92]CI 95%;p=0.001) and although late-onset VAP in patients significantly often was associated with kidney failure (OR 2.95[075-6.32]CI 95%;p=0.003) and septic shock 3.68[1.05-8.21] CI95%;p=0.001).In all early-onset pneumonia patients ,bacterial pathogens were most commonly gram positive bacteria(100%) and 80%(4/5) were susceptible to cefotaxime, cefepime, piperacillin-tazobactam, and meropenem.Conversely, in late-onset VAP, most bacterial pathogens were gram-negative bacteria(29/30) and muti-drug resistant (MDR)pathogens(14/30).Among MDR gram-negative bacteria causing late-onset VAP, most commonly was obtained Acinotebacter baumannii(9/30),followed Pseudomonas aeruginosa(6/30),folowed Klebsiella pneumoniae (5/30) and Escherichia coli(5/30) and Aspergillus fumigates(5/30).And just 13% of patients with late-onset VAP were susceptible to piperacillin-tazobactam,17% were susceptible to cefepime and 34% were susceptible to meropenem.Late-onset VAP was associated with high mortality rate among intubated compared to early-onset VAP and non-VAP patients ( OR 4.87[1,54-10.32] CI95%;p=0.001;OR 6.33[1.58-14.25] CI 95%;p=0.0008).Conclusions:Secondary bacterial co-infection is common in intubated critically ill patients with COVID19 and most commonly presentation of bacterial infection is late-onset VAP causing by multi-drug resitant pathogens which are associated commonly with ARDS, kidney failure and septic shock.In patients with late-onset VAP MDR pathogens may predict high mortality rate.

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2nd International Conference on Computational Intelligence and Internet of Things (ICCIIoT 2021)

Preface:We are pleased to present this volume of the selected contributed articles, submitted and presented in the 2nd International Conference on Computational Intelligence and Internet of Things (ICCIIoT 2021) which held on February 23-24, 2022 (initially planned on November 22 & 23, 2021 but postponed due to COVID19) at Department of Electronics and Communication Engineering, North Eastern Regional Institute of Science and Technology (NERIST), Arunachal Pradesh, India, in collaboration with International Association of Academicians (IAASSE), USA. (Conference link: http://icciiot.iaasse.org/.)The 2nd International Conference on Computational Intelligence and Internet of Things (ICCIIoT 2021) is the 2nd in the series) is a platform for researchers, engineers, academicians as well as industrial professionals from all over the world to present their research results and development activities in Computational Intelligence and Internet of Things. The event (ICCIIoT 2021) took place in hybrid model and thereby allowing some authors to present their papers virtually because of Covid–19 and the government’s restriction on any gathering. And by that, organizers fulfilled their commitments with researchers and supports the scientific research. The eminent professors and experts in their fields were invited to deliver their speech at ICCIIoT 2021.List of Acknowledgment, Disclaimer, Guest Editors are available in this pdf.

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Twitter and Instagram Use in the Urology Residency Application Process

OBJECTIVE: To define urology applicant attitudes and usage trends of social media (SM) during the 2021 urology match cycle. METHODS: We emailed an anonymous, de-identified 22-question, multiple choice survey to all applicants to our institution for the 2021 Urology Residency Match. We asked participants about use of SM and which aspects they found useful in the application process. Univariate descriptive analyses were conducted based on survey responses. Chi-square analyses were performed to define significant differences in use of social media and resultant match outcomes. RESULTS: Of the 528 students who registered for the 2021 AUA Match, 398 received our survey (75%), and 144 responded (27% of applicants nationwide). Of survey participants, 49% made a new account on Twitter while 30% had a preexisting account. Most participants (71%) had a preexisting Instagram account, while only 3% made a new account. Most participants agreed Twitter was used as a source to gather information about programs (84%) and learn about events (89%). Participants found SM most helpful for announcing event dates (71%) and highlighting resident social life (59%). Applicants did not match more highly on their rank lists if they used Twitter (P = .427) or Instagram (P = .166) and were not more likely to get more interviews if they used Twitter (P = .246) or Instagram (P = .114) CONCLUSION: Applicants found Twitter to be an important source of information through the virtual interview process. Despite the use of SM by most applicants, published content did not impact rank list decisions nor did SM engagement predict match outcomes.

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Defending Density

We have an aversion to density in America. Density is a continual trope in this country, blamed for all of the ills of urban life, from crime and racial unrest in the middle of the 20th century to public health concerns today. In the early stages of the COVID pandemic density was the culprit, even though we’ve subsequently seen outbreaks in rural areas and sprawling cities across the United States. This paper will look into the root of America’s problems with density and argue that density is not the problem but the solution to the challenges of today’s and tomorrow’s cities. As we deplete the resources of the planet, density is our most direct pathway to recover some balance with nature. Dense living is more efficient, less carbon intensive and more environmentally sustainable. As geospatial differentiations matter less due to advances in communication technology, it's the density of people and ideas that will continue to fuel innovation. Finally, in a world that is increasingly dominated by pluralism, denser living promotes openness, tolerance and diversity.

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A Prospective Study of Mental Health, Well-Being, and Substance Use During the Initial COVID-19 Pandemic Surge.

The COVID-19 pandemic has dramatically altered everyday life worldwide, and some individuals may be at increased risk for pandemic-related distress. In a U.S. community sample (N = 236, 64% female; 78% White; M age = 30.3) assessed prior to COVID-19 and during the initial surge, we examined, prospectively, whether pandemic disruptions and a history of adverse childhood experiences (ACEs) were associated with changes in depressive symptoms, stress, sleep, relationship satisfaction, and substance use over time, and with concurrent anxiety and peritraumatic distress. Negative pandemic-related events were associated with significantly higher depressive symptoms and stress and lower satisfaction over time, as well as higher concurrent anxiety and peritraumatic distress. ACEs were associated with more negative pandemic-related events, which in turn associated with higher peri-pandemic depressive symptoms, stress, anxiety, and peritraumatic distress. Findings underscore that COVID-19 disruptions are associated with greater distress, and that childhood trauma is a key axis of differential risk.

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Perceptions, feelings, and the routine of older adults during the isolation period caused by the COVID-19 pandemic: a qualitative study in four countries.

OBJECTIVE To evaluate the knowledge, routine, and perception of older adults from four countries about dealing with COVID-19 in the social isolation period. METHODS Qualitative study with semistructured interviews. Older persons (≥60 years old), who lived in the urban centers of four different countries (Brazil, United States, Italy, and Portugal), were asked about the changes experienced during the pandemic, new habits or restrictions during isolation, sources of social and emotional support, and their knowledge about COVID-19 pandemic. Data was transcribed, codified, and submitted to content analysis. RESULTS Twenty-five older persons (10 from Brazil, 5 from Italy, 5 from Portugal, and 5 from the United States) were interviewed. Participants reported feeling restricted in their daily life activities and emotional instability. Described adaptations in habits, coping strategies, and greater understanding of the diseased based on information available in the media. There was homogeneity in the statements of the elderly, showing that the pandemic affected them in a similar way, even though they lived in different cultures and contexts. CONCLUSION The social isolation caused by the COVID-19 pandemic changed the structure for the performance of many occupations, having an impact in the perception social participation and wellbeing of elders. This data can aid health professionals to outline strategies to deal with the impact of the social isolation in older persons.

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Pastoral Care at the Time of Lockdown: An Exploratory Study of the Catholic Church in South Tyrol (Italy)

In order to assess the impact of COVID-19 on catholic pastoral care, an exploratory study was conducted in South Tyrol (Italy) by administering an online survey to parish priests and laypeople with an office within the local Diocese. With reference to the lockdown period, the research aimed to investigate: (1) how pastoral care was delivered;(2) changes in the use of ICT within religious activities;and (3) the vision of the future for the Church in a mediatized world. Respondents believe that: (1) pastoral activities have slowed down, even though contact with the faithful was kept up through phone or the Internet;(2) the level of digitalization of the parishes has increased;however, the communication was mostly one-way and top-down. Finally, results show that (3) attitudes towards digital media are divergent: they are perceived as having the potential to either strengthen or weaken the relationship between the Church and the faithful.

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Disparities in case frequency and mortality of coronavirus disease 2019 (COVID-19) among various states in the United States

OBJECTIVE: To utilize publicly reported, state-level data to identify factors associated with the frequency of cases, tests, and mortality in the USA. MATERIALS AND METHODS: Retrospective study using publicly reported data collected included the number of COVID-19 cases, tests and mortality from March 14th through April 30th. Publicly available state-level data was collected which included: demographics comorbidities, state characteristics and environmental factors. Univariate and multivariate regression analyses were performed to identify the significantly associated factors with percent mortality, case and testing frequency. All analyses were state-level analyses and not patient-level analyses. RESULTS: A total of 1,090,500 COVID-19 cases were reported during the study period. The calculated case and testing frequency were 3332 and 19,193 per 1,000,000 patients. There were 63,642 deaths during this period which resulted in a mortality of 5.8%. Factors including to but not limited to population density (beta coefficient 7.5, p < .01), transportation volume (beta coefficient 0.1, p < .01), tourism index (beta coefficient −0.1, p = .02) and older age (beta coefficient 0.2, p = .01) are associated with case frequency and percent mortality. CONCLUSIONS: KEY MESSAGES: There were wide variations in testing and case frequencies of COVID-19 among different states in the USA. States with higher population density had a higher case and testing rate. States with larger population of elderly and higher tourism had a higher mortality.

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Validation of Fabric-Based Thigh-Wearable EMG Sensors and Oximetry for Monitoring Quadriceps Activity during Strength and Endurance Exercises

Muscle oximetry based on near-infrared spectroscopy (NIRS) and electromyography (EMG) techniques in adherent clothing might be used to monitor the muscular activity of selected muscle groups while exercising. The fusion of these wearable technologies in sporting garments can allow the objective assessment of the quality and the quantity of the muscle activity as well as the continuous monitoring of exercise programs. Several prototypes integrating EMG and NIRS have been developed previously; however, most devices presented the limitations of not measuring regional muscle oxyhemoglobin saturation and did not embed textile sensors for EMG. The purpose of this study was to compare regional muscle oxyhemoglobin saturation and surface EMG data, measured under resting and dynamic conditions (treadmill run and strength exercises) by a recently developed wearable integrated quadriceps muscle oximetry/EMG system adopting smart textiles for EMG, with those obtained by using two "gold standard" commercial instrumentations for EMG and muscle oximetry. The validity and agreement between the wearable integrated muscle oximetry/EMG system and the "gold standard" instrumentations were assessed by using the Bland-Altman agreement plots to determine the bias. The results support the validity of the data provided by the wearable electronic garment developed purposely for the quadriceps muscle group and suggest the potential of using such device to measure strength and endurance exercises in vivo in various populations.

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The predictors of high titer of anti-SARS-CoV-2 antibody of convalescent plasma donors

Background: Recent evidence suggested that the higher titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody from convalescent plasma donors contributed to the clinical improvement in coronavirus disease 2019 (COVID-19) patients. However, the titers of anti-SARS-CoV-2 antibodies varied in each individual, and the precise factors that might govern such variation have not been elucidated. Objectives: To assess the factors associated with high titers of anti-SARS-CoV-2 antibody among COVID-19 convalescent plasma (CCP) donors. Methods: A cross-sectional study was conducted in Saiful Anwar General Hospital, Malang, Indonesia. Information of interest including demographic characteristics, clinical symptoms, comorbidities, laboratory findings, and the titers of anti-SARS-CoV-2 antibody among COVID-19 CCP donors were collected. The correlation was assessed using multiple logistic regression. Results: A total of 50 COVID-19 CCP donors with the titers of anti-SARS-CoV-2 antibody of more than 1:320 and 33 donors with the titers of less than 1:320 were analyzed. Our analysis revealed that CCP donors with history of cough, fever, dyspnea, and pneumonia significantly had higher titers of anti-SARS-CoV-2 antibody compared to asymptomatic donors. Moreover, CCP donors with elevated levels of eosinophils and immature granulocytes and low levels of albumins had higher levels of anti-SARS-CoV-2 antibody. The titer of antibody was not affected by comorbidities of donors. Conclusions: CPP donors who had experience of symptomatic COVID-19 with high eosinophils level, high immature granulocytes and low albumin level have higher titers of anti-SARS-COV-2 antibody than those who experienced asymptomatic COVID-19. Our current findings may be used as the additional baseline criteria for selecting the donors of CCP for the management of COVID-19.

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Les symptômes du bas appareil urinaire et pneumopathie COVID-19 : quels liens ?

Introduction Les pneumopathies infectieuses liées au COVID-19 présentent actuellement un motif fréquent d’hospitalisation aux services de pneumologie. Il s’agit d’une pathologie potentiellement grave notamment sur le plan respiratoire. Par ailleurs, plusieurs autres atteintes peuvent être associées pouvant altérer la qualité de vie des patients. Peu d’études se sont intéressées à décrire les symptômes du bas appareil urinaire au cours de l’infection à COVID-19. L’objectif de notre travail était de dépister les symptômes urinaires associés à l’infection COVID-19 et de déterminer leur prévalence en fonction de la sévérité du tableau clinique. Méthodes Nous avons mené une étude descriptive faisant inclure 51 patients hospitalisés au service de pneumologie de l’hôpital militaire de Tunis entre mars et août 2021. Le recueil des données clinicobiologiques et radiologiques a été rétrospectif. Le dépistage des signes urinaires a été réalisé en utilisant le Questionnaire de Symptômes Urinaires USP (Urinary Symptom Profile), à travers un entretien téléphonique. Les données ont été saisies et analysées à l’aide du logiciel SPSS version 25. Résultats Notre population comportait 22 femmes (41,5 %) et 29 hommes (54,7 %), avec un âge moyen de 54,86±16 ans. Aucun de nos patients n’avait un antécédent urinaire antérieur à l’infection COVID-19. Les signes du bas appareil urinaires retrouvés chez nos patients étaient : une incontinence urinaire (58 %), une hyperactivité vésicale (68,3 %) et une dysurie (14,6 %). L’étendue des lésions pulmonaires scanographiques étaient réparties comme suit : étendue légère (10–25 %) : 13,5 % ; étendue modérée (25–50 %) : 11,5 % et étendue sévère (>50 %) : 69,2 %. Sur le plan clinique l’hyperactivité vésicale, la dysurie et l’incontinence urinaire étaient significativement corrélées à une prévalence plus importante de formes sévères (p =0,003, p =0,03 et p =0,01 respectivement). L’hyperactivité vésicale a été significativement associée à une atteinte scanographique étendue (p =0,003), à une procalcitonine positive (p =0,001) et à une hyperfibrinogénémie (p =0,03). Aucune corrélation n’a été retrouvée entre l’hyperactivité vésicale et l’augmentation de la C reactive protein (CRP). Conclusion Notre étude a mis l’accent sur la prévalence des symptômes du bas appareil urinaire chez les sujets atteints de pneumopathie type COVID-19. D’autres travaux prospectifs sont nécessaires afin de déterminer le mécanisme physiopathologique et la valeur pronostique des atteintes urinaires.

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A dry lab for medical engineers?

INTRODUCTION We describe a teaching and training method with objective evaluation to improve medical engineering students' knowledge and analysis skills about Minimally Invasive Surgery (MIS) instrumentation and techniques through hands-on experience. Training has been scheduled during a three-month course. METHODS Twenty medical engineering students were trained to perform three times on a pelvic trainer a sequence of standardized drills connected with the selected MIS techniques, in order to improve their dexterity. The time required to perform each dexterity drill was recorded in seconds.Then, the participants were divided into groups and asked to write an essay about an instrument they chose, analyzing and criticizing the instrument itself. RESULTS All the trainees showed steady improvement in skill acquisition on the laparoscopic simulator and discussed their essays, making proposals in order to improve the instrument they tested. CONCLUSION Significant improvement in performance with increasing skillness has been measured; during the course and during their discussion the participants showed deep knowledge of the instrument, ability to analyze and criticize it and ability to make improvement proposals.Dry lab experience for medical engineering students is useful for teaching and improving analysis and management of laparoscopic devices, allowing identification of problems and developing better devices.

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Vitamin D, zinc and glutamine: Synergistic action with OncoTherad immunomodulator in interferon signaling and COVID­19 (Review)

Coronavirus disease 2019 (COVID­19), caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), was identified in December, 2019 in Wuhan, China. Since then, it has continued to spread rapidly in numerous countries, while the search for effective therapeutic options persists. Coronaviruses, including SARS­CoV­2, are known to suppress and evade the antiviral responses of the host organism mediated by interferon (IFN), a family of cytokines that plays an important role in antiviral defenses associated with innate immunity, and has been used therapeutically for chronic viral diseases and cancer. On the other hand, OncoTherad, a safe and effective immunotherapeutic agent in the treatment of non­muscle invasive bladder cancer (NMIBC), increases IFN signaling and has been shown to be a promising therapeutic approach for COVID­19 in a case report that described the rapid recovery of a 78­year­old patient with NMIBC with comorbidities. The present review discusses the possible synergistic action of OncoTherad with vitamin D, zinc and glutamine, nutrients that have been shown to facilitate immune responses mediated by IFN signaling, as well as the potential of this combination as a therapeutic option for COVID­19.

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Arterio-ureteral fistula: a nationwide cross-sectional questionnaire analysis

PURPOSE: Arterio-ureteral fistula (AUF) is an uncommon diagnosis, but potentially lethal. Although the number of reports has increased over the past two decades, the true incidence and contemporary urologists’ experience and approach in clinical practice remains unknown. This research is conducted to provide insight in the incidence of AUF in The Netherlands, and the applied diagnostic tests and therapeutic approaches in modern practice. METHODS: A nationwide cross-sectional questionnaire analysis was performed by sending a survey to all registered Dutch urologists. Data collection included information on experience with patients with AUF; and their medical history, diagnostics, treatment, and follow-up, and were captured in a standardized template by two independent reviewers. Descriptive statistics were used. RESULTS: Response rate was 62% and 56 AUFs in 53 patients were reported between 2003 and 2018. The estimated incidence of AUF in The Netherlands in this time period is 3.5 AUFs per year. Hematuria was observed in all patients; 9% intermittent microhematuria, and 91% presenting with, or building up to massive hematuria. For the final diagnosis, angiography was the most efficient modality, confirming diagnosis in 58%. Treatment comprised predominantly endovascular intervention. CONCLUSION: The diagnosis AUF should be considered in patients with persistent intermittent or massive hematuria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00345-021-03910-3.

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IoT PULSE OXIMETRY STATUS MONITORING FOR HOME QUARANTINED COVID-19 PATIENTS

This article represents a prototype experiment regarding the practical implementation of an affordable, wireless, and online monitoring pulse oximetry device, for a Covid-19 infected patient that is quarantined at home By using an Arduino based IoT (Internet of Things) embedded platform and a free online API (Application Programming Interface) live data stream server, the family physician can remotely monitor the patient's pulse and blood oxygen level, by using a mobile phone, a tablet or a computer, without any contamination risk or contact, with the infected patient

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The influence of HLA genotype on the severity of COVID-19 infection

The impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID-19 infection. Forty-nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P = .003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01-DQB1*05:01-DRB1*01:01 in the asymptomatic group compared to the background population (P = .007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID-19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities.

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LY6E impairs coronavirus fusion and confers immune control of viral disease

Zoonotic coronaviruses (CoVs) are substantial threats to global health, as exemplified by the emergence of two severe acute respiratory syndrome CoVs (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV) within two decades1-3. Host immune responses to CoVs are complex and regulated in part through antiviral interferons. However, interferon-stimulated gene products that inhibit CoVs are not well characterized4. Here, we show that lymphocyte antigen 6 complex, locus E (LY6E) potently restricts infection by multiple CoVs, including SARS-CoV, SARS-CoV-2 and MERS-CoV. Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in immune cells were highly susceptible to a murine CoV-mouse hepatitis virus. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic immune cells, higher splenic viral burden and reduction in global antiviral gene pathways. Accordingly, we found that constitutive Ly6e directly protects primary B cells from murine CoV infection. Our results show that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo-knowledge that could help inform strategies to combat infection by emerging CoVs.

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A review on Remdesivir: A broad-spectrum antiviral molecule for possible COVID-19 treatment.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was identified to have emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering has led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials researchers worldwide are currently using available conventional therapeutic drugs with potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to show promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID-19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.

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12-month randomised trial of 360° and 180° Schlemm's canal incisions in suture trabeculotomy ab interno for open-angle glaucoma.

BACKGROUND/AIMS To perform a 12-month comparison between the different extents and locations of Schlemm's canal incisions during suture trabeculotomy ab interno for open-angle glaucoma (OAG). METHODS This is a prospective, single-centre, three-arm randomised trial. A total of 99 eyes of 99 patients were randomly assigned to one of three groups: the 360° incision group (n=34), the upper-180° incision group (n=34) and the lower-180° incision group (n=31). Intraocular pressure (IOP), number of medications and complications were evaluated until 12 months after surgery. Surgical success (with or without medication) was defined as IOP ≤21 mmHg and ≥20% IOP reduction (criterion A) or IOP ≤15 mmHg and ≥20% IOP reduction (criterion B). RESULTS The mean IOP (±SD) in all eyes was reduced from 18.6 (5.9) mmHg with 3.1 (1.1) medications to 13.7 (3.4) mmHg (20.8% reduction; p<0.001) with 1.4 (1.3) medications (p<0.001) at postoperative 12-month. Each group produced comparable mean reductions in both IOP and the number of medications throughout 12 months of follow-up. Kaplan-Meier cumulative survival analyses showed no significance among these three groups for criterion A and criterion B. Postoperative hyphema with niveau formation occurred significantly more in the 360° group than in the lower-180° group (p=0.031). CONCLUSIONS The different extents and locations of Schlemm's canal incisions during suture trabeculotomy ab interno for OAG, including the 360° incision, the upper-180° incision and the lower-180° incision, do not affect both the IOP reduction and the medications throughout 12 months of follow-up. TRIAL REGISTRATION NUMBER UMIN000021169.

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Strategies for mitochondrial gene editing

Mitochondria, as the energy factory of cells, participate in metabolism processes and play a critical role in the maintenance of human life activities. Mitochondria belong to semi-automatic organelles, which have their own genome different from nuclear genome. Mitochondrial DNA (mtDNA) mutations can cause a series of diseases and threaten human health. However, an effective approach to edit mitochondrial DNA, though long-desired, is lacking. In recent years, gene editing technologies, represented by restriction endonucleases (RE) technology, zinc finger nuclease (ZFN) technology, transcription activator-like effector nuclease (TALEN) technology, CRISPR system and pAgo-based system have been comprehensively explored, but the application of these technologies in mitochondrial gene editing is still to be explored and optimized. The present study highlights the progress and limitations of current mitochondrial gene editing technologies and approaches, and provides insights for development of novel strategies for future attempts.

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Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations

The neonatal fragment crystallizable (Fc) receptor (FcRn) functions as a recycling mechanism to prevent degradation and extend the half-life of IgG and albumin in the circulation. Several FcRn inhibitors selectively targeting IgG recycling are now moving rapidly toward clinical practice in neurology and hematology. These molecules accelerate the destruction of IgG, reducing pathogenic IgG and IgG immune complexes, with no anticipated effects on IgA, IgM, IgE, complement, plasma cells, B cells, or other cells of the innate or adaptive immune systems. FcRn inhibitors have potential for future use in a much wider variety of antibody-mediated autoimmune diseases. Given the imminent clinical use, potential for broader utility, and novel mechanism of action of FcRn inhibitors, here we review data from 4 main sources: (a) currently available activity, safety, and mechanism-of-action data from clinical trials of FcRn inhibitors; (b) other procedures and treatments that also remove IgG (plasma donation, plasma exchange, immunoadsorption); (c) diseases resulting in loss of IgG; and (d) primary immunodeficiencies with potential mechanistic similarities to those induced by FcRn inhibitors. These data have been evaluated to provide practical considerations for the assessment, monitoring, and reduction of any potential infection risk associated with FcRn inhibition, in addition to highlighting areas for future research.

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The impact of Post-COVID-Syndrome on functioning – results from a community survey in patients after mild and moderate SARS-CoV-2-infections in Germany

BACKGROUND: In COVID-19 survivors a relatively high number of long-term symptoms have been observed. Besides impact on quality of life, these symptoms (now called Post-COVID-Syndrome) may have an impact on functioning and may also hinder to participation in social life in affected people. However, little is known about developing such syndrome a for patients with mild and moderate COVID-19 who did not need hospitalization or intensive care. METHODS: A cross-sectional study in 1027 patients with mild or moderate COVID-19 was performed in two communities in Bavaria, Germany. The Rehabilitation-Needs-Survey (RehabNeS) including the Short Form 36 Health Survey (SF-36) on health-related quality of life, was used. Descriptive statistics were calculated. RESULTS: In all, 97.5% of patients reported one symptom in the infection stage, such as fatigue, respiratory problems, limitations of the senses of taste and smell, fear and anxiety and other symptoms. In this time period, 84.1% of the participants experienced activity limitations and participation restrictions such as carrying out daily routines, handling stress, getting household tasks done, caring for/supporting others, and relaxing and leisure concerns. In all, 61.9% of participants reported persisting symptoms more than 3 months after infection. These were fatigue, sleep disturbances, respiratory problems, pain, fear and anxiety, and restrictions in movement; 49% of the participants reported activity limitations and participation restrictions. Predominately, these were handling stress, carrying out daily routines, looking after one’s health, relaxing and leisure activities and doing house work. The impacts on quality of life and vocational performance were rather low. CONCLUSION: The results show that long-term symptoms after mild and moderate COVID-19 are common and lead to limitations of activities and participation. However, it seems that in most cases they are not severe and do not lead to frequent or serious issues with quality of life or work ability.

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Ribavirin therapy for severe COVID-19: a retrospective cohort study

The aim of this study was to compare ribavirin therapy versus supportive therapy only for patients with severe coronavirus disease 2019 (COVID-19). A total of 115 patients with laboratory-confirmed COVID-19 were retrospectively analysed. All patients received supportive care as well as regular laboratory and clinical monitoring. The 115 patients comprised 44 patients who received intravenous ribavirin (treatment group) and 71 who did not (control group). Baseline laboratory and clinical characteristics were similar between the two groups. The negative conversion time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR in the ribavirin group was 12.8 ± 4.1 days compared with 14.1 ± 3.5 days in the control group (P = 0.314). Moreover, 7/41 patients (17.1%) in the ribavirin group died compared with 17/69 (24.6%) in the control group (P = 0.475). Adverse effects were similar between the two groups. In conclusion, in patients with severe COVID-19, ribavirin therapy is not associated with improved negative conversion time for SARS-CoV-2 test and is not associated with an improved mortality rate. Further assessment in designed randomised controlled trials is recommended.

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“Alternative” Endocytic Mechanisms Exploited by Pathogens: New Avenues for Therapeutic Delivery?

Some pathogens utilize unique routes to enter cells that may evade the intracellular barriers encountered by the typical clathrin-mediated endocytic pathway. Retrograde transport and caveolar uptake are among the better characterized pathways, as alternatives to clathrin-mediated endocytosis, that are known to facilitate entry of pathogens and potential delivery agents. Recent characterization of the trafficking mechanisms of prion proteins and certain bacteria may present new paradigms for strategizing improvements in therapeutic spread and retention of therapy. This review will provide an overview of such endocytic pathways, and discuss current and future possibilities in using these routes as a means to improve therapeutic delivery.

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Study on Factors of People’s Wearing Masks Based on Two Online Surveys: Cross-Sectional Evidence from China

(1) Background: To analyze factors of people’s wearing masks based on two online surveys, and to explore whether living area factor or quarantine status could have an impact on mask-wearing. (2) Methods: Chi-square test and logistic regression analysis were used to explore the influence of different factors on people’s behavior of mask-wearing in the present study. R3.6.2 was used for data cleaning, SPSS 26.0 was used to conduct corresponding statistical analysis, and a two-sided p-value less than 0.05 was considered to be statistically significant. (3) Results: According to our study, the proportion of participants who wore face masks was higher than 90.0% in both surveys. Single factor analysis showed that the proportion of people wearing face masks raised with the increase of people’s education, age, and monthly income (Yuan) in both surveys. People who lived in rural areas were less likely to wear masks. Mask-wearing rate was lower in the isolated individuals than in the non-isolated ones. (4) Conclusions: Masks-wearing is one of the effective measures for COVID-19 pandemic prevention and control. After the Chinese government made wearing face masks mandatory in public places, most residents in China had developed the habit of wearing masks, contributing to the high rate of masks-wearing in China. However, people in rural areas need to raise their awareness of wearing masks. Meanwhile, the mask-wearing of the isolated individuals needs to be enhanced.

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Active pulmonary tuberculosis and coronavirus disease 2019: A systematic review and meta-analysis

OBJECTIVE: The proportion of COVID-19 patients having active pulmonary tuberculosis, and its impact on COVID-19 related patient outcomes, is not clear. We conducted this systematic review to evaluate the proportion of patients with active pulmonary tuberculosis among COVID-19 patients, and to assess if comorbid pulmonary tuberculosis worsens clinical outcomes in these patients. METHODS: We queried the PubMed and Embase databases for studies providing data on (a) proportion of COVID-19 patients with active pulmonary tuberculosis or (b) severe disease, hospitalization, or mortality among COVID-19 patients with and without active pulmonary tuberculosis. We calculated the proportion of tuberculosis patients, and the relative risk (RR) for each reported outcome of interest. We used random-effects models to summarize our data. RESULTS: We retrieved 3,375 citations, and included 43 studies, in our review. The pooled estimate for proportion of active pulmonary tuberculosis was 1.07% (95% CI 0.81%-1.36%). COVID-19 patients with tuberculosis had a higher risk of mortality (summary RR 1.93, 95% CI 1.56–2.39, from 17 studies) and for severe COVID-19 disease (summary RR 1.46, 95% CI 1.05–2.02, from 20 studies), but not for hospitalization (summary RR 1.86, 95% CI 0.91–3.81, from four studies), as compared to COVID-19 patients without tuberculosis. CONCLUSION: Active pulmonary tuberculosis is relatively common among COVID-19 patients and increases the risk of severe COVID-19 and COVID-19-related mortality.

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COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning

To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane (M) protein, have been tested for vaccine development against SARS and MERS. However, these vaccine candidates might lack the induction of complete protection and have safety concerns. We then applied the Vaxign and the newly developed machine learning-based Vaxign-ML reverse vaccinology tools to predict COVID-19 vaccine candidates. Our Vaxign analysis found that the SARS-CoV-2 N protein sequence is conserved with SARS-CoV and MERS-CoV but not from the other four human coronaviruses causing mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10), were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and the predicted linear B-cell epitopes were found to be localized on the surface of the protein. Our predicted vaccine targets have the potential for effective and safe COVID-19 vaccine development. We also propose that an "Sp/Nsp cocktail vaccine" containing a structural protein(s) (Sp) and a non-structural protein(s) (Nsp) would stimulate effective complementary immune responses.

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441 Cutaneous findings in COVID-19 patients hospitalized at a large urban academic medical center

Background: Cutaneous manifestations have been associated with COVID-19 infection and their clinical significance in hospitalized patients remains unclear Methods: A retrospective chart review of 1216 patients older than 18 years of age hospitalized with laboratory-confirmed SARS-CoV-2 infection from March 12, 2020 to May 31, 2020 at a large urban academic medical center A keyword search query of patient records combined with manual chart review by at least two dermatologists identified a study group having cutaneous manifestations concurrent with COVID-19 infection, specifically between 14 days prior to admission and up to discharge Results: 122 patients with 195 skin lesions concurrent with COVID-19 hospitalization were identified Dermatology reviewers evaluated clinical photographs for 116 lesions (59 5%) and inpatient dermatology consultations for 42 lesions (21 5%) The most common cutaneous findings in patients with COVID-19 hospitalization were pressure injuries (n=118;60 5%) and morbilliform eruptions (n=33;16 9%) A very small number of patients (0 6%;n=7/1216) had exanthems occurring within 2 weeks of COVID-19 symptom onset The majority of exanthems developed within 14 days of exposure to possible culprit drugs and beyond the 14-day window of COVID-19 symptom onset, making viral association unlikely Conclusion: Skin lesions concurrent with COVID-19 hospitalization were most frequently linked to hospitalization-related factors, such as pressure injuries or drug-related exanthems, rather than due to novel pathologies related to SARS-CoV-2 itself

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Preventing the Transmission of COVID-19 in Older Adults Aged 60 Years and Above Living in Long-Term Care: Rapid Review Update

Objectives: The objective of this study was to examine the effect of measures of control and management of COVID-19, Middle East Respiratory Syndrome (MERS), and severe acute respiratory syndrome (SARS) in adults 60 years or above living in long-term care facilities. This is an update of previous work done by Rios et al. Methods: A rapid review was conducted in accordance with the Rapid Review Guide for Health Policy and Systems Research. Literature search of databases MEDLINE, Cochrane library, and pre-print servers (biorxiv/medrxiv) was conducted from July 31, 2020 to October 9, 2020. EMBASE was searched from July 31, 2020 until October 18, 2020. Titles and abstracts from public archives were identified for screening using Gordon V. Cormack and Maura R. Grossmans Continuous Active Learning (CAL) tool, which uses supervised machine learning. Results: Five observational studies and one clinical practice guideline were identified. Infection prevention measures identified in this rapid review included: social distancing and isolation, personal protective equipment (PPE) use and hygiene practices, screening, training and staffing policies. The use of PPE, laboratory screening tests, sick pay to staff, self-confinement of staff within the LTCFs for 7 or more days, maintaining maximum resident occupancy, training and social distancing significantly reduced the prevalence of COVID-19 infection among residents and/or staff of LTCFs (p<0.05). Practices such as hiring of temporary staff, not assigning staff to care separately for infected and uninfected residents, inability to isolate sick residents and infrequent cleaning of communal areas significantly increased the prevalence of infection among residents and/or staff of LTCFs (p<0.05). Conclusion: The available studies are limited to only three countries despite the global nature of the disease. The majority of these studies showed that infection control measures such as favourable staffing policies, training, screening, social distancing, isolation and use of PPE significantly improved residents and staff related outcomes. More studies exploring the effects infection prevention and control practices in long term care facilities are required.

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Dr.supER: Intubation and ventilator troubleshooting VR simulation

This paper presents Virtual Reality 3D interaction and simulation techniques in the context of the 2021 3DUI contest of the IEEE VR conference In our implementation, by taking into consideration the current COVID-19 pandemic situation, we developed a VR gamified simulation regarding the intubation and ventilator troubleshooting procedures, taking place in an Emergency Room (E R ) In this paper, we present the design and development of the overall experience, aiming to train the end-user on these actions to enhance their possibilities of achieving optimal performance under stressful situations By gamifying the above education system, we also expect to empathize the layman regarding the daily challenges that the medical staff is experiencing in an Intensive Care Unit © 2021 IEEE

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Artificial Intelligence and Blockchain Integration in Business: Trends from a Bibliometric-Content Analysis

Artificial intelligence (AI) and blockchain are the two disruptive technologies emerging from the Fourth Industrial Revolution (IR4.0) that have introduced radical shifts in the industry. The amalgamation of AI and blockchain holds tremendous potential to create new business models enabled through digitalization. Although research on the application and convergence of AI and blockchain exists, our understanding of the utility of its integration for business remains fragmented. To address this gap, this study aims to characterize the applications and benefits of integrated AI and blockchain platforms across different verticals of business. Using bibliometric analysis, this study reveals the most influential articles on the subject based on their publications, citations, and importance in the intellectual network. Using content analysis, this study sheds light on the subject’s intellectual structure, which is underpinned by four major thematic clusters focusing on supply chains, healthcare, secure transactions, and finance and accounting. The study concludes with 10 application areas in business that can benefit from these technologies.

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"We will be in touch". A neuroscientific assessment of remote vs. face-to-face job interviews via EEG hyperscanning.

In the last decades, improving remote communications in companies has been a compelling issue. With the outspread of SARS-CoV-2 pandemic, this phenomenon has undergone an acceleration. Despite this, little to no research, considering neurocognitive and emotional systems, was conducted on job interview, a critical organizational phase which significantly contributes to a company long-term success.In this study, we aimed at exploring the emotional and cognitive processes related to different phases of a job interview (introductory, attitudinal, technical and conclusion), when considering two conditions: face-to-face and remote, by simultaneously gathering EEG (frequency bands: alpha, beta, delta, and theta) and autonomic data (skin-conductance-level, SCL, skin-conductance-response, SCR, and heart rate, HR) in both candidates and recruiters. Data highlighted a generalized alpha desynchronization during the job interview interaction. Recruiters showed increased frontal theta activity, which is connected to socio-emotional situations and emotional processing. In addition, results showed how face-to-face condition is related to increased SCL and theta power in the central-brain area, associated with learning processes, via the mid-brain dopamine system and the anterior cingulate cortex. Furthermore, we found higher HR in the candidates. Present results call to re-examine the impact of information-technology in the organization, opening to translational opportunities.

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Planning for the Post-COVID Syndrome: How Payers Can Mitigate Long-Term Complications of the Pandemic

As the COVID-19 pandemic continues to unfold, payers across the USA have stepped up to alleviate patients’ financial burden by waiving cost-sharing for COVID-19 testing and treatment. However, there has been no substantive discussion of potential long-term effects of COVID-19 on patient health or their financial and policy implications. After recovery, patients remain at risk for lung disease, heart disease, frailty, and mental health disorders. There may also be long-term sequelae of adverse events that develop in the course of COVID-19 and its treatment. These complications are likely to place additional medical, psychological, and economic burdens on all patients, with lower-income individuals, the uninsured and underinsured, and individuals experiencing homelessness being most vulnerable. Thus, there needs to be a comprehensive plan for preventing and managing post-COVID-19 complications to quell their clinical, economic, and public health consequences and to support patients experiencing delayed morbidity and disability as a result.

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The 501Y.V2 SARS-CoV-2 variant has an intermediate viral load between the 501Y.V1 and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients

The 501Y.V2 and the 501Y.V1 SARS-CoV-2 variants emerged and spread rapidly into the world. We analysed the RT-PCR cycle threshold values of 643 nasopharyngeal samples of COVID-19 patients at diagnosis and found that the 501Y.V2 variant presented an intermediate viral load between the 501Y.V1 and the historical variants.

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Critical Care Response to the Outbreak of COVID-19: The Experience From Guangdong Province, China

In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was confirmed in Wuhan, China, and spread rapidly beyond Wuhan and around the world. By 7 May 2020, a total of 84,409 patients were infected in mainland China, with 4,643 deaths, according to a Chinese Center for Disease Control and Prevention report. Recent studies reported that critically ill patients were presented with high mortality. However, the clinical experiences of patients with coronavirus disease 2019 (COVID-19) have not been described in Guangdong Province, where by 7 May 2020, 1,589 people had been confirmed as having COVID-19 but with a very low mortality of 8 death (0.5%). Here, we describe the experience of critical care response to the outbreak of SARS-CoV-2 in Guangdong Province in the following points: Early intervention by the government, Establishment of a Multidisciplinary Working Group, Prompt intensive care interventions, Adequate ICU beds and Human resource in ICU, Infection control practices.

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New adaptation of neurosurgical practice and residency programs during the Covid-19 pandemic and their effects on neurosurgery resident satisfaction and welfare at the National General Hospital, Jakarta, Indonesia

INTRODUCTION: Many institutions in numerous countries have made changes in their health care services during the COVID-19 pandemic. One change has been to reduce elective neurosurgery cases, which has impacted neurosurgery education. Published literature is lacking about the healthcare services, education, and residents’ well-being during adaptation to the pandemic, especially in national referral hospitals in developing countries. METHODS: We conducted a cross-sectional study on current neurosurgical services during 2020. We evaluated 34 neurosurgery residents in Cipto Mangunkusumo National General Hospital using a self-made questionnaire to determine the effects of the COVID-19 pandemic on their surroundings, education process, and satisfaction with the currently adapted education program. We used the modified Maslach Burnout Inventory to assess burnout in the residents before and during the pandemic. RESULTS: Neurosurgical residents spent more time studying neurosurgical theory (Mode 1–1.5h/day, p < 0.05) but spent less time learning neurosurgical skills (Mode 30 min–1 h/day, p < 0.05) compared to before the pandemic. The resident satisfaction mean score (scale 0–10) was 7.58 for live surgery and 8.53 for the microsurgical skills lab training program. On a scale of 1–10, the residents’ stress level increased after the pandemic but the change was not statistically significant (6.61 ± 1.87, p > 0.05). The Modified Maslach Burnout inventory score was 3.02 ± 3.74 during the pandemic, and increased from before the pandemic (2.41 ± 3.18), but the difference was not statistically significant. CONCLUSION: The COVID-19 pandemics have reduced the working hours and the clinical exposure of neurosurgical residents. Fortunately, this pandemic has led to a new opportunity to find many suitable learning methods which may decrease the risk of burnout. The psychological burden of residents is still worrisome, and planned management is necessary to sustain resident performance.

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High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.

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Risk of COVID-19 infection in patients with rheumatic disease taking disease-modifying anti-rheumatic drugs

BACKGROUND AND OBJECTIVE: Patients with rheumatic disease taking long-term disease-modifying anti-rheumatic drugs (DMARDs) are expected to have a higher risk of infection due to the alterations in cellular immunity associated with these medications. However, the potential risks associated with these drugs remain unclear. This study aimed to estimate the risk of COVID-19 infection in patients with rheumatic disease taking disease-modifying anti-rheumatic drugs. METHODS: Patients with autoimmune rheumatic disease taking DMARDs with or without long-term (> 6 months) HCQ treatment prior to the COVID-19 outbreak were selected consecutively. The diagnosis of COVID-19 was made based on the history of symptoms suggestive of the disease and/or serum IgG positivity. During statistical analysis, the risk of COVID-19 infection was calculated in rheumatic patients taking DMARDs versus controls, as well as in patients taking HCQ versus those who are not. The ORs and 95% CIs were also calculated. The participants in the control group were selected from individuals without RD. RESULTS: A total of 800 patients with RD and 449 controls were analyzed. COVID-19 infection was detected in 16.8% of rheumatic patients versus 17.6% of controls (OR 0.95; 95% CI 0.7-1.28). The proportions of COVID-19 infection in HCQ users versus non-users were 15.3% and 18.1%, respectively (OR 0.87; 95% CI 0.61-1.26). These results remained unchanged after adjusting for all covariates using logistic regression analysis. CONCLUSION: These findings indicate that rheumatic patients taking DMARDs are not at a higher risk of COVID-19 infection, and that HCQ therapy has no influence on the risk of COVID-19 infection. Key points • The risk of COVID-19 infection is not higher in patients with RD on DMARD therapy. • The prevalence of COVID-19 infection in HCQ users has not significant difference relative to non-users. • Significant percent of RD patients taking DMARDs had asymptomatic infection. • There was a positive association between leflunamide therapy and the risk of COVID-19 infection.

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Efficacy of porcine acellular dermal matrix in the management of lower eyelid retraction: case series and review of the literature.

PURPOSE To investigate the efficacy of Permacol™, a decellularized porcine dermal-derived membrane, as a spacer in the management of lower eyelid retraction. The efficacy of sizing and insertion was investigated, as well as complications. The literature was also reviewed to compare this material with other porcine-derived grafts in use for the management of lower eyelid retraction. METHODS This was a retrospective case series observing all patients who received lower eyelid Permacol implants by the two senior authors (AAM, TGH) for the management of lower eyelid retraction. Patient demographics, indications for surgery, graft size, degree of postoperative lid advancement, and complications were reviewed. RESULTS A total of 12 patients (16 eyelids) received Permacol implants for correction of lower eyelid retraction during the study period of 18 months (January 2015 to July 2017). Ten procedures were related to thyroid eye disease, 3 for reconstruction, 2 postcosmetic lower lid blepharoplasty, and one acquired anophthalmic socket. The average preoperative inferior scleral show (ISS) was 1.74 mm, and the average postoperative ISS was 0.82 mm. There was a mean lower eyelid elevation of 0.91 mm (p < 0.005, Wilcoxon signed rank test) and mean ratio of graft height:preoperative ISS was 3.8:1 over a median of 8 months follow-up. CONCLUSIONS Permacol is a safe and effective alternative to autologous tissues for use as a spacer in patients with lower eyelid retraction of varying etiologies. It does undergo some resorption with time, however this can be predicted and incorporated into surgical planning; we recommend an implant height:ISS ratio of 4:1.

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The Combined Value of Type2 Inflammatory Markers in Chronic Obstructive Pulmonary Disease

The roles of type2 inflammatory markers in chronic airway diseases have been assessed in previous studies. However, the relationship between the combined value of these biomarkers and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. We aimed to investigate the roles of the combined value of the fraction of exhaled nitric oxide (FeNO) level and blood eosinophil count in COPD and the predictive capability of these biomarkers. In total, 266 patients were included in our analysis. When the two type2 biomarkers were assessed separately, there were limited correlations between either increased FeNO level or blood eosinophil count and decreased incidence of total exacerbation or frequency of mild exacerbation. Combining these two biomarkers strengthened their association with both incidence and frequency of acute exacerbation. In addition, during further assessment, simultaneously increased FeNO level and blood eosinophil count were associated with both mild and moderate acute exacerbation. Among the subjects included in this analysis, although the predictive capability was improved when these two biomarkers were combined, the improvement was not statistically significant, indicating the need to increase the sample size. The combination of FeNO level and blood eosinophil count exhibited strong and independent additive value in the assessment of acute exacerbation in COPD; simultaneously increased FeNO level and blood eosinophil count played a protective role in progression of COPD.

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Covid-19: factors associated with emotional distress and psychological morbidity in spanish population./ COVID-19: Factores asociados al malestar emocional y morbilidad psiquica en poblacion espanola

OBJECTIVE: The socio-health emergency caused by COVID-19 may have a significant psychological impact on the population For this reason, it is necessary to identify especially vulnerable social groups and protective factors that may reduce this impact, which was the objective of this study METHODS: Using snowball sampling approach, 1,596 people residing in Spain during the lockdown answered an online questionnaire that included information on sociodemographic variables, symptoms, and contact with the disease, risk perception, precautionary measures to prevent infection and coping strategies during lockdown Psychological impact was assessed using the Impact of Event Scale-Revised (IES-R), and mental health status with the Goldberg's General Health Questionnaire (GHQ-12) Simple linear regression models were performed to analyze the associations between the study variables and the psychological impact of the pandemic and the mental health of the participants RESULTS: Of all respondents, 24 7% reported a moderate or severe psychological impact, and 48 8% showed mental health problems Women, students and the population with a lower level of economic income, in addition to those having less available space per person in the household presented a more significant psychological impact and worse mental health Living with someone from the high-risk vulnerable group, and anticipating the adverse economic effects of social-health crisis raised the emotional distress and psychological morbidity Precautionary measures to prevent infection did not present a connection to the psychological impact of the pandemic;however, several coping strategies did help to reduce it CONCLUSIONS: These findings outline the existence of especially vulnerable social groups to the impact of the pandemic, and suggest lines of action that help reduce the psychosocial consequences of COVID-19 OBJETIVO: La emergencia socio-sanitaria provocada por la COVID-19 puede tener un importante impacto psicologico en la poblacion Por este motivo, resulta necesario identificar los grupos sociales especialmente vulnerables al impacto de la pandemia y los factores de proteccion que pueden reducirlo, lo que constituyo el objetivo de este estudio METODOS: Mediante muestreo tipo bola de nieve, 1 596 personas residentes en Espana durante la cuarentena contestaron un cuestionario online que incluyo informacion sobre variables sociodemograficas, sintomas y contacto con la enfermedad, percepcion del riesgo, conductas para prevenir el contagio y estrategias para afrontar la cuarentena El impacto psicologico se evaluo mediante la Escala de Impacto de Evento-Revisada (IES-R), y el estado de salud mental con el Cuestionario de Salud General de Goldberg (GHQ-12) Mediante diferentes modelos de regresion lineal simple se analizo la relacion de las variables del estudio con el impacto psicologico de la pandemia y la salud mental de los participantes RESULTADOS: El 24,7% de los participantes presento un impacto psicologico moderado o severo y el 48,8% mostro deterioro de la salud mental Las mujeres, los estudiantes y la poblacion con menor nivel de ingresos economicos, ademas de con menos espacio disponible por persona en la vivienda, presentaron mayor impacto psicologico y peor salud mental Convivir con personas de riesgo y prever los efectos economicos negativos de la crisis socio-sanitaria elevaron el malestar emocional y la morbilidad psiquica Aunque las medidas para prevenir el contagio no se relacionaron con el impacto psicologico, determinadas estrategias de afrontamiento si ayudaron a reducirlo CONCLUSIONES: Estos hallazgos perfilan la existencia de determinados grupos sociales especialmente sensibles al impacto de la pandemia, y sugieren lineas de accion que ayuden a reducir las secuelas psicosociales de la COVID-19

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Current status of COVID-19 pandemic; characteristics, diagnosis, prevention, and treatment

Humans have always been encountered to big infectious diseases outbreak throughout the history. In December 2019, novel coronavirus (COVID-19) was first noticed as an agent causing insidious pneumonia in Wuhan, China. COVID-19 was spread rapidly from Wuhan to the rest of the world. Until late June 2020, it infected more than 10,000,000 people and caused more than 500,000 deaths in almost all of countries in the world, creating a global crisis worse than all previous epidemics and pandemics. In the current review, we gathered and summarized the results of various studies on characteristics, diagnosis, treatment, and prevention of this pandemic crisis.

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A high-throughput approach to profile RNA structure

Here we introduce the Computational Recognition of Secondary Structure (CROSS) method to calculate the structural profile of an RNA sequence (single- or double-stranded state) at single-nucleotide resolution and without sequence length restrictions. We trained CROSS using data from high-throughput experiments such as Selective 2΄-Hydroxyl Acylation analyzed by Primer Extension (SHAPE; Mouse and HIV transcriptomes) and Parallel Analysis of RNA Structure (PARS; Human and Yeast transcriptomes) as well as high-quality NMR/X-ray structures (PDB database). The algorithm uses primary structure information alone to predict experimental structural profiles with >80% accuracy, showing high performances on large RNAs such as Xist (17 900 nucleotides; Area Under the ROC Curve AUC of 0.75 on dimethyl sulfate (DMS) experiments). We integrated CROSS in thermodynamics-based methods to predict secondary structure and observed an increase in their predictive power by up to 30%.

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Cell-penetrating peptides as transporters for morpholino oligomers: effects of amino acid composition on intracellular delivery and cytotoxicity

Arginine-rich cell-penetrating peptides (CPPs) are promising transporters for intracellular delivery of antisense morpholino oligomers (PMO). Here, we determined the effect of L-arginine, D-arginine and non-α amino acids on cellular uptake, splice-correction activity, cellular toxicity and serum binding for 24 CPP−PMOs. Insertion of 6-aminohexanoic acid (X) or β-alanine (B) residues into oligoarginine R(8) decreased the cellular uptake but increased the splice-correction activity of the resulting compound, with a greater increase for the sequences containing more X residues. Cellular toxicity was not observed for any of the conjugates up to 10 μM. Up to 60 μM, only the conjugates with ⩾ 5 Xs exhibited time- and concentration-dependent toxicity. Substitution of L-arginine with D-arginine did not increase uptake or splice-correction activity. High concentration of serum significantly decreased the uptake and splice-correction activity of oligoarginine conjugates, but had much less effect on the conjugates containing X or B. In summary, incorporation of X/B into oligoarginine enhanced the antisense activity and serum-binding profile of CPP−PMO. Toxicity of X/B-containing conjugates was affected by the number of Xs, treatment time and concentration. More active, stable and less toxic CPPs can be designed by optimizing the position and number of R, D-R, X and B residues.

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The public health emergency management system in China: trends from 2002 to 2012

BACKGROUND: Public health emergencies have challenged the public health emergency management systems (PHEMSs) of many countries critically and frequently since this century. As the world’s most populated country and the second biggest economy in the world, China used to have a fragile PHEMS; however, the government took forceful actions to build PHEMS after the 2003 SARS outbreak. After more than one decade’s efforts, we tried to assess the improvements and problems of China’s PHEMS between 2002 and 2012. METHODS: We conducted two rounds of national surveys and collected the data of the year 2002 and 2012, including all 32 provincial, 139 municipal, and 489 county CDCs. The municipal and county CDCs were selected by systematic random sampling. Twenty-one indicators of four stages (preparation, readiness, response and recovery) from the National Assessment Criteria for CDC Performance were chosen to assess the ten-year trends. RESULTS: At the preparation stage, organization, mechanisms, workforce, and stockpile across all levels and regions were significantly improved after one decade’s efforts. At the readiness stage, the capability for formulating an emergency plan was also significantly improved during the same period. At the response stage, internet-based direct reporting was 98.8%, and coping scores were nearly full points of ten in 2012. At the recovery stage, the capabilities were generally lower than expected. CONCLUSIONS: Due to forceful leadership, sounder regulations, and intensive resources, China’s PHEMS has been improved at the preparation, readiness, and response stages; however, the recovery stage was still weak and could not meet the requirements of crisis management and preventive governance. In addition, CDCs in the Western region and counties lagged behind in performance on most indicators. Future priorities should include developing the recovery stage, establishing a closed feedback loop, and strengthening the capabilities of CDCs in Western region and counties.

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Emergency management of nursing human resources and supplies to respond to coronavirus disease 2019 epidemic

Objective: To introduce the emergency management of nursing human resources and material resources of a large general hospitals when facing the outbreak of the coronavirus disease 2019(COVID-19). Method: The Nursing Department of the hospital fully executed its functional authority to establish a three-level echelon of sustainable support, allocate human recourses dynamically, organize pre-service training, supervise the key working steps, formulate positive incentive methods, and deploy medical supplies scientifically. Result: By taking these strategies, the hospital effectively improved the coping capacity of the nursing team and played a positive role in the prevention and treatment of COVID-19. Conclusion: The emergency management of nursing human resources and material resources for COVID-19 of the hospital is successful. But several deficiencies were identified as well, which indicated that the hospital needs to establish an efficient emergency management system, and pay attention to the practice of nursing emergency plans to enhance coping capacities in public health emergencies.

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Polyoxovanadates with emerging biomedical activities

Polyoxovanadates (POVs) are a subclass of a larger family of polyanionic group V and VI metal-oxo clusters that are known as polyoxometalates (POMs). POMs have been found to have antidiabetic, antibacterial, antiprotozoal, antiviral and anticancer activities, which have sparked interest in their use as bioinorganic drugs. Among POVs, decavanadate ([V10O28]6−;V10) is an isopolyoxovanadate recently described to have several medicinal applications. In the present review, recent insights into POVs with emergent anticancer, antimicrobial and antiviral applications are described. Additionally, POVs’ stability and speciation under experimental biological conditions as well as POVs (in particular, V10) in vivo and ex-vivo effects are highlighted. Finally, we report the most important 21st century studies of POVs’ effects and/or targets against cancer, bacteria and viruses including: apoptosis, cell cycle arrest, interference with ions transport system, inhibition of mRNA synthesis, cell morphology changes, changes in metabolic pathways, phosphorylase enzyme inhibition and cell signaling, formation of reactive oxygen species, lipid peroxidation, inhibition of viral mRNA polymerase, inhibition of virus binding to the host cell, penetration and interaction with virus protein cages.

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A data driven agent-based model that recommends non-pharmaceutical interventions to suppress Coronavirus disease 2019 resurgence in megacities

Before herd immunity against Coronavirus disease 2019 (COVID-19) is achieved by mass vaccination, science-based guidelines for non-pharmaceutical interventions are urgently needed to reopen megacities. This study integrated massive mobile phone tracking records, census data and building characteristics into a spatially explicit agent-based model to simulate COVID-19 spread among 11.2 million individuals living in Shenzhen City, China. After validation by local epidemiological observations, the model was used to assess the probability of COVID-19 resurgence if sporadic cases occurred in a fully reopened city. Combined scenarios of three critical non-pharmaceutical interventions (contact tracing, mask wearing and prompt testing) were assessed at various levels of public compliance. Our results show a greater than 50% chance of disease resurgence if the city reopened without contact tracing. However, tracing household contacts, in combination with mandatory mask use and prompt testing, could suppress the probability of resurgence under 5% within four weeks. If household contact tracing could be expanded to work/class group members, the COVID resurgence could be avoided if 80% of the population wear facemasks and 40% comply with prompt testing. Our assessment, including modelling for different scenarios, helps public health practitioners tailor interventions within Shenzhen City and other world megacities under a variety of suppression timelines, risk tolerance, healthcare capacity and public compliance.

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Inclusive purchasing and supply chain resilience capabilities: Lessons for social sustainability

In the face of unexpected changes in their dynamic business environment, purchasing and supply chain (SC) managers have been challenged to boost SC resilience while maintaining their sustainability concerns. In this changing environment, this paper aims to explore: (1) how (social) sustainability affects SC resilience and (2) what the role of purchasing is for SC resilience. Through a dynamic capability view as the theoretical lens, we investigate whether and how an inclusive purchasing programme could enhance SC resilience capabilities to cope with the Covid-19 outbreak. We developed a Case study with various SC members of a multinational cosmetics company that, despite suffering from a sudden demand disruption during the outbreak, maintained its sustainability actions. The results show that four operational SC resilience capabilities were amplified: ‘visibility’, ‘adaptability’, ‘collaboration’ and ‘financial strength’. In addition, a new capability entitled ‘empowerment’ was mobilised during this period. These factors helped the inclusive purchasing maintenance and were essential to supporting social sustainability. In addition, our results show that sustainable PSM, which is overlooked in the literature, is key for SC resilience. This article contributes to theory and practice because it demonstrates the role and relevance of (inclusive) purchasing in a company's ability to cope with SC disruptions, such as those resulting from the outbreak.

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Does health securitization affect the role of global surgery?

Aim: More and more frequently outbreaks of infectious diseases force the international community to urgent health action and lead to an increasing security focus on global health. Considering the limiting character of resource allocation, all other medical conditions must compete with the top spot of health security matters, as we currently see with the outbreak of COVID-19. Surgery is an integral part of universal health offering life-saving therapy for a variety of illnesses. Amidst the increasing nexus of infectious diseases and health security and in the view of Public Health Emergencies of International Concern (PHEIC), is there a risk of global surgery falling behind? Subject and Methods: While the global undersupply of surgical care is well recorded, contextual explanations are absent. Our research introduces the constructivist concept of securitization according to the Copenhagen School to explain the structural handicap of global surgery and by that presents a structural explanation. We investigate the securitizing potential of surgical diseases in comparison to infectious diseases. Results: Surgical conditions are non-contagious without the risk for disease outbreaks, hardly preventable and their treatment is often infrastructurally demanding. These key features mark their low securitizing potential. Additionally, as PHEIC is the only securitizing institution in the realm of health, infectious diseases have a privileged role in health security. Conclusion: Surgery substantially lacks securitizing potential in comparison to communicable diseases and by that is structurally given an inferior position in a securitized health order.

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Reply to: Comment on Predicting In‐Hospital Mortality in COVID‐19 Older Patients with Specifically Developed Scores

This letter comments on the letter by Alain Putot

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Key dimer interface residues impact the catalytic activity of 3CLpro, the main protease of SARS-CoV-2

3C-like protease (3CLpro) is one of two proteases that process and liberate functional viral proteins essential for the maturation and infectivity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. It has been suggested that 3CLpro is catalytically active as a dimer, making the dimerization interface a target for antiviral development. Guided by structural analysis, here we introduced single amino acid substitutions at nine residues at three key sites of the dimer interface to assess their impact on dimerization and activity. We show that at site 1, alanine substitution of S1 or E166 increased by 2-fold or reduced relative activity, respectively. At site 2, alanine substitution of S10 or E14 eliminated activity, whereas K12A exhibited ∼60% relative activity. At site 3, alanine substitution of R4, E290, or Q299 eliminated activity, whereas S139A exhibited 46% relative activity. We further found the oligomerization states of the dimer interface mutants varied;the inactive mutants R4A, R4Q, S10A/C, E14A/D/Q/S, E290A, and Q299A/E were present as dimers, demonstrating that dimerization is not an indication of catalytically active 3CLpro. In addition, present mostly as monomers, K12A displayed residual activity, which could be attributed to the conspicuous amount of dimer present. Finally, differential scanning calorimetry did not reveal a direct relationship between the thermodynamic stability of mutants with oligomerization or catalytic activity. These results provide insights on two allosteric sites, R4/E290 and S10/E14, that may promote the design of antiviral compounds that target the dimer interface rather than the active site of SARS-CoV-2 3CLpro.

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SARS-like coronaviruses in horseshoe bats (Rhinolophus spp.) in Russia, 2020

We found and genetically described two novel SARS-like coronaviruses in feces and oral swabs of the great (R. ferrumequinum) and the lesser (R. hipposideros) horseshoe bats in southern region of Russia. The viruses, named Khosta-1 and Khosta-2, together with related viruses from Bulgaria and Kenya, form a separate phylogenetic lineage. We found an evidence of recombination events in evolutionary history of Khosta-1, which involved the acquisition of structural proteins S, E, and M as well as nonstructural genes ORF3, ORF6, ORF7a, and ORF7b from a virus that is closely related to Kenyan isolate BtKY72. Examination of bats by RT-PCR revealed that 62,5% of great horseshoe bats in one of the caves were positive for Khosta-1 virus while its overall prevalence was 14%. The prevalence of Khosta-2 was 1,75%. Our results show that SARS-like coronaviruses circulate in horseshoe bats in the region and provide a new data on their genetic diversity.

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Evaluation of Student Core Drives on e-Learning during the Covid-19 with Octalysis Gamification Framework

Learning activities during the Covid-19 pandemic were carried out with an online system even though in reality many institutions had not prepared their systems and infrastructure properly Some e-learning media that are generally used based on survey results include 53 81% google classrooms combined with other applications that are not integrated with the institution’s Learning Management System This condition provides research opportunities to evaluate the effectiveness of online learning, especially how students are motivated to learn the method, where the results can be used as a reference in developing and refining the method Based on many studies, that the gamification model can increase individual motivation in carrying out activities, this study uses a gamification octalysis framework to analyze the extent of the role of gamification in the learning process and measure the amount of student motivation in online learning activities The evaluation results show that the conclusion of the Likert scale results in a “High” level, while the highest score is “Very High” As for the octalysis test scale, the average score of 6 5 on a scale of 1 to 10 The conclusion from the results of this evaluation is that the motivation to learn e-learning during the Covid-19 period is quite high and has the potential to be developed While the results of the Octalysis framework with 8 core drives are still average, for that we need innovation in E-learning which aims to increase student motivation based on Octalysis’s 8 core drives The results of this study recommend that gamification is needed to increase student learning motivation in order to improve learning outcomes © 2020 All Rights Reserved

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Data-Driven Modeling Reveals the Impact of Stay-at-Home Orders on Human Mobility during the COVID-19 Pandemic in the U.S

One approach to delay the spread of the novel coronavirus (COVID-19) is to reduce human travel by imposing travel restriction policies. It is yet unclear how effective those policies are on suppressing the mobility trend due to the lack of ground truth and large-scale dataset describing human mobility during the pandemic. This study uses real-world location-based service data collected from anonymized mobile devices to uncover mobility changes during COVID-19 and under the 'Stay-at-home' state orders in the U.S. The study measures human mobility with two important metrics: daily average number of trips per person and daily average person-miles traveled. The data-driven analysis and modeling attribute less than 5% of the reduction in the number of trips and person-miles traveled to the effect of the policy. The models developed in the study exhibit high prediction accuracy and can be applied to inform epidemics modeling with empirically verified mobility trends and to support time-sensitive decision-making processes.

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Postoperative fever in the time of COVID-19

Summary: Postoperative fever is common following orthopedic trauma surgery. As the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases in the community, migration into the acute care hospital setting intensifies, creating confusion when fever develops postoperatively. The transmission dynamics of SARS-CoV-2 make it difficult to adequately gauge and pinpoint risk groups with questionnaires at the time of hospital admission. This is particularly problematic when asymptomatic or presymptomatic patients infected with SARS-CoV-2 require urgent surgery and cannot be screened effectively. One approach is to treat every patient as though they were SARS-CoV-2-positive in preparation for surgery, but doing so could exacerbate shortages of personal protective equipment and staffing limitations. Uncertainty regarding the etiology of postoperative fever could be significantly reduced by universal SARS-CoV-2 testing of all surgical patients at the time of hospital admission in addition to routine screening, but testing capacity and a rapid turnaround time would be required.

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Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India

BACKGROUND: ZyCoV-D, a DNA-based vaccine, showed promising safety and immunogenicity in a phase 1/2 trial. We now report the interim efficacy results of phase 3 clinical trial with ZyCoV-D vaccine in India. METHODS: We conducted an interim analysis of a multicentre, double-blind, randomised, placebo-controlled phase 3 trial at 49 centres in India. Healthy participants aged at least 12 years were enrolled and randomly assigned (1:1) to receive either ZyCov-D vaccine (Cadila Healthcare; 2 mg per dose) or placebo. An interactive web response system was used for randomisation (blocks of four) of participants as well as to enrol those aged 60 years and older with or without comorbid conditions, and those aged 12–17 years. It was also used to identify 600 participants for immunogenicity (blocks of six). Participants, investigators, and outcome assessors were masked to treatment assignment. Three doses of vaccine or placebo were administered intradermally via a needle-free injection system 28 days apart. The primary outcome was the number of participants with first occurrence of symptomatic RT-PCR-positive COVID-19 28 days after the third dose, until the targeted number of cases (interim analysis n=79, full analysis n=158) have been achieved. The analysis was done in the per-protocol population, which consisted of all participants with negative baseline SARS-CoV-2 status who received three doses of vaccine or placebo. Assessment of safety and tolerability was based on the safety population, which consisted of all enrolled participants who were known to have received at least one dose of study vaccine or placebo. This trial is registered with Clinical Trial Registry India, CTRI/2021/01/030416, and is ongoing. FINDINGS: Between Jan 16, and June 23, 2021 (data cutoff), 33 194 individuals were screened, of whom 5241 did not meet screening criteria and 27 703 were enrolled and randomly assigned to receive ZyCoV-D (n=13 851) or placebo (n=13 852). Per-protocol, 81 cases were eligible and included in efficacy analysis (20 of 12 350 in the ZyCoV-D group and 61 of 12 320 in placebo group). The ZyCoV-D vaccine efficacy was found to be 66·6% (95% CI 47·6–80·7). The occurrence of solicited adverse events was similar between the treatment groups (623 [4·49%] in the ZyCoV-D group vs 620 [4·47%] in the placebo group). There were two deaths (one in each group) reported at the data cutoff, neither of which was considered related to the study treatments. INTERPRETATION: In this interim analysis, ZyCoV-D vaccine was found to be efficacious, safe, and immunogenic in a phase 3 trial. FUNDING: National Biopharma Mission, Department of Biotechnology, Government of India and Cadila Healthcare, Ahmedabad, Gujarat India.

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Reduction in Long-term Mortality after Sleeve Gastrectomy and Gastric Bypass Compared to Non-surgical Patients with Severe Obesity

OBJECTIVE: To separately compare the long-term risk of mortality among bariatric surgical patients undergoing either RYGB or SG to large, matched, population-based cohorts of patients with severe obesity who did not undergo surgery. BACKGROUND: Bariatric surgery has been associated with reduced long-term mortality compared to usual care for severe obesity which is particularly relevant in the COVID-19 era. Most prior studies involved the Roux-en-Y gastric bypass (RYGB) operation and there is less long-term data on the sleeve gastrectomy (SG). METHODS: In this retrospective, matched cohort study, patients with a body mass index ≥35 kg/m2 who underwent bariatric surgery from January 2005 to September 2015 in three integrated health systems in the United States were matched to nonsurgical patients on site, age, sex, body mass index, diabetes status, insulin use, race/ethnicity, combined Charlson/Elixhauser comorbidity score, and prior health care utilization, with follow-up through September 2015. Each procedure (RYGB, SG) was compared to its own control group and the two surgical procedures were not directly compared to each other. Multivariable-adjusted Cox regression analysis investigated time to all-cause mortality (primary outcome) comparing each of the bariatric procedures to usual care. Secondary outcomes separately examined the incidence of cardiovascular-related death, cancer related-death, and diabetes related-death. RESULTS: Among 13,900 SG, 17,258 RYGB, and 87,965 nonsurgical patients, the 5-year follow-up rate was 70.9%, 72.0%, and 64.5%, respectively. RYGB and SG were each associated with a significantly lower risk of all-cause mortality compared to nonsurgical patients at 5-years of follow-up (RYGB: HR = 0.43; 95% CI: 0.35,0.54; SG: HR = 0.28; 95% CI: 0.13,0.57) Similarly, RYGB was associated with a significantly lower 5-year risk of cardiovascular- (HR = 0.27; 95% CI: 0.20, 0.37), cancer- (HR = 0.54; 95% CI: 0.39, 0.76), and diabetes-related mortality (HR = 0.23; 95% CI:0.15, 0.36). There was not enough follow-up time to assess 5-year cause-specific mortality in SG patients, but at 3-years follow up, there was significantly lower risk of cardiovascular- (HR = 0.33; 95% CI:0.19, 0.58), cancer- (HR = 0.26; 95% CI:0.11, 0.59), and diabetes-related (HR = 0.15; 95% CI:0.04, 0.53) mortality for SG patients. CONCLUSION: This study confirms and extends prior findings of an association with better survival following bariatric surgery in RYGB patients compared to controls and separately demonstrates that the SG operation also appears to be associated with lower mortality compared to matched control patients with severe obesity that received usual care. These results help to inform the trade-offs between long-term benefits and risks of bariatric surgery.

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Machine Learning and Image Analysis Applications in the Fight against COVID-19 Pandemic: Datasets, Research Directions, Challenges and Opportunities

COVID-19 pandemic has become the most devastating disease of the current century and spread over 216 countries around the world. The disease is spreading through outbreaks despite the availability of modern sophisticated medical treatment. Machine Learning and Image Analysis research has been making great progress in many directions in the healthcare field for providing support to subsequent medical diagnosis. In this paper, we have propose three research directions with methodologies in the fight against the pandemic namely: Chest X-Ray (CXR) images classification using deep convolution neural networks with transfer learning to assist diagnosis; Patient Risk prediction of pandemic based on risk factors such as patient characteristics, comorbidities, initial symptoms, vital signs for prognosis of disease; and forecasting of disease spread & case fatality rate using deep neural networks. Further, some of the challenges, open datasets and opportunities are discussed for researchers.

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We, who haven't been diagnosed, are sort of out of the pictureâ?' breathless without a diagnosis: The UK covid-19 lockdown experience

Aim To describe experiences during the COVID-19 pandemic of people living with chronic breathlessness without a diagnosis Methods As part of a wider mixed methods study (Breathlessness-DiagnosE Early in Primary care: Breathe-DEEP), semistructured interviews were undertaken with people referred for investigation of chronic breathlessness across ten GP practices The interview guide included questions around experiences of breathlessness, healthcare interactions and the impact of COVID-19 pandemic Telephone interviews were audiorecorded, transcribed, coded and reviewed by the study team using thematic analysis Results Over six weeks during the UK lockdown for the COVID-19 pandemic, 20 participants were interviewed (12 female, mean age 65 yrs) Five participants lived alone, two were working and three recently received a confirmed diagnosis for their breathlessness None of the participants experienced COVID-19 Three key themes were identified 1 Unintentional de-prioritisation of diagnosis by patients The COVID-19 pandemic has led to a reduction in seeking healthcare for this group Some described their breathlessness as a 'non-urgent' problem, and others felt worried about burdening their GP and the National Health Service (NHS) at this time 2 Following UK 'lockdown' guidance for the general population, is this enough? This group are not identified as vulnerable but have a clear perception that they are at increased risk if they were to contract COVID-19 3 Impact of lockdown on coping strategies for managing breathlessness People have expressed modified behaviour to help them cope with lockdown Some people are obliged by the nature of lockdown to use disengaged coping strategies which has a negative impact on managing their breathlessness and mental health Conclusion The existing unpredictable pathway to diagnosis for people living with chronic breathlessness has been further interrupted during the COVID-19 pandemic People expressed concern about only following general population advice, rather than shielding, due to not having a diagnosis Patients and clinicians need to re-engage with the pathway to diagnosis and management of chronic breathlessness

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Feasibility of a new approach for creating a preperitoneal space in transabdominal preperitoneal repair inguinal hernia repair: using a sandwich approach.

PURPOSE In Japan, transabdominal preperitoneal (TAPP) inguinal hernia repair is performed by firmly pulling the peritoneum inwards to lift it from the underlying deep layer of subperitoneal fascia. It decreases the postoperative pain and discomfort in the inguinal area. The aim of this study was to evaluate the feasibility of the sandwich approach, which is a new technique for creating a preperitoneal space. METHODS The operation was performed via the sandwich approach. We made sure to protect the preperitoneal fascia areolar layer when making the preperitoneal space. RESULTS We performed TAPP in 745 patients (876 hernias) treated between October 2006 and April 2015 at Himeji Medical Center and Kurashiki Central Hospital. Before October 2010, we did not use the sandwich approach, and recurrence was observed in three patients. From October 2010, we always used the sandwich approach and never experienced any cases of recurrence. Clavien-Dindo classification Grade 3 or higher postoperative complications occurred in 6 patients (0.8%) between October 2006 and April 2015. Mesh-related ileus was the most frequently observed morbidity. There were no cases of vas differentia or spermatic vessel injury, postoperative chronic pain, or urinary retention. CONCLUSION The sandwich approach is feasible as another standard dissective procedure for TAPP.

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Grief: The Epidemic Within an Epidemic

COVID-19 has not only dramatically changed the way we live, it has also impacted how we die and how we grieve. With more and more Americans dying in ICU settings, away from family, and more funerals being held virtually, the pandemic has seriously curtailed normal expressions of grief and cultural mourning. Given the CDC guidelines for funerals and social distancing, simple human touch is no longer a mitigating force against prolonged grief. So, while one epidemic has a face and a name, we point to a second, more silent yet potentially equally devastating one, unacknowledged grief, and emphasize how policy can be a current therapeutic. We can wait for a vaccine, but we can also act now through thoughtful policymaking that acknowledges this second epidemic.

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Allosteric inhibition induces an open WPD-loop: a new avenue towards glioblastoma therapy

The mobility of loops around the catalytic site of a protein remains crucial to its activity. Dynamics of the WPD-loop is an essential determinant of the catalytic activity of tyrosine-protein phosphatase zeta, an implicated protein in glioblastoma cells. The WPD-loop assumes a closed conformation upon substrate binding in order to position its catalytic aspartate to participate in catalysis. Herein, we explore the impact of NAZ2329, a recently identified allosteric inhibitor of tyrosine-protein phosphatase zeta, on the atomic flexibility of the WPD-loop. The druglikeness of NAZ2329 was assessed using the SwissADME online tool. The enzymatic complex was then subjected to conformational simulations using the AMBER molecular dynamics software. Structural analysis revealed that NAZ2329 induced an open conformation of the crucial WPD-loop, consequently impeding enzyme activity even upon substrate binding. Based on the molecular interactions between NAZ2329 and tyrosine-protein phosphatase zeta, a pharmacophore model was generated to exhibit the important functional moieties of NAZ2329. These findings provide an insightful molecular and structural mechanism in targeting tyrosine-protein phosphatase zeta as a therapeutic intervention for glioblastoma. We believe that this optimized pharmacophoric model will aid in the design of improved anti-tyrosine phosphatase agents, thus allowing for increased patient adherence.

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Covid-19 Pandemic- Pits and falls of major states of India.

Covid-19, just like SARS and MERS before it, is a disease caused by corona virus and can lead to severe respiratory diseases in humans. With the outbreak of novel corona virus, WHO on 30th January 2020 declared it a Public Health Emergency and further on 11th March 2020, Covid-19 disease was declared a pandemic. India in the initial stages of the pandemic dealt with it in a very effective manner. With timely implementation of lockdown, India was able to contain the spread of Covid-19 to some extent. However with the recently announced Unlock 1.0, the SARS CoV-2 is expected to spread. This study aims to track and analyze the Covid-19 situation in major states that constitute of 70 percent of the total cases. Thus the states selected for the study are: Maharashtra, Delhi, Tamil Nadu, Gujarat, Uttar Pradesh and Rajasthan. These are the states which had more than ten thousand Covid-19 patients as/on June 10th 2020. The analysis period is from March 25th to June 10th and the data source is India Covid-19 tracker. To assess the previous and current Covid-19 situations in these states indicators such as Active rates, Recovery rate, Case fatality rate, Test positivity rate, tests per million, cases per million, test per confirmed case has been used. The study finds that although the absolute number of active cases may be rising, however it is showing a decreasing trend with an increase in recovery rates. With increasing number of Covid-19 cases, testing also has increased however not in the similar proportion and thus by developed nation standard we are lagging. With increasing TPR and cases per million, Delhi is well on its way to surpass even Mumbai which till now has proven to be worst hit in this pandemic. An interesting finding is that of test per confirmed case which shows that every 6th person in Maharashtra and every 8th in Delhi is showing positive result of Covid-19 test. Given such an increase and unlocked India, Delhi might soon enter into the third stage of community transmission where source of 50 percent or more cases would be unknown. There has been an increase in the Covid-19 related health infrastructure with the public-private partnership which involved both private hospitals and lab joining hands to battle Covid-19, however, affordability still remains an issue. If experts are to be believed, pandemic is not over because we have unlocked. The worst is yet to come as Covid-19 is predicted to peak in mid-July to August in India. Thus, it would be advisable to not venture out unnecessarily just because restrictions have been lifted. Also, following the guidelines- hand-washing, avoiding public gathering, social distancing and covering nose and mouth has now become imperative.

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High Mobility Group Box 1 and Interleukin 6 at Intensive Care Unit Admission as Biomarkers in Critically Ill COVID-19 Patients

Exuberant inflammation manifesting as a “cytokine storm” has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO(2)/FiO(2) < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.

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The influence of awareness campaigns on the spread of an infectious disease: a qualitative analysis of a fractional epidemic model

Mass-media coverage is one of the most widely used government strategies on influencing public opinion in times of crisis. Awareness campaigns are highly influential tools to expand healthy behavior practices among individuals during epidemics and pandemics. Mathematical modeling has become an important tool in analyzing the effects of media awareness on the spread of infectious diseases. In this paper, a fractional-order epidemic model incorporating media coverage is presented and analyzed. The problem is formulated using susceptible, infectious and recovered compartmental model. A long-term memory effect modeled by a Caputo fractional derivative is included in each compartment to describe the evolution related to the individuals’ experiences. The well-posedness of the model is investigated in terms of global existence, positivity, and boundedness of solutions. Moreover, the disease-free equilibrium and the endemic equilibrium points are given alongside their local stabilities. By constructing suitable Lyapunov functions, the global stability of the disease-free and endemic equilibria is proven according to the basic reproduction number [Formula: see text] . Finally, numerical simulations are performed to support our analytical findings. It was found out that the long-term memory has no effect on the stability of the equilibrium points. However, for increased values of the fractional derivative order parameter, each solution reaches its equilibrium state more rapidly. Furthermore, it was observed that an increase of the media awareness parameter, decreases the magnitude of infected individuals, and consequently, the height of the epidemic peak.

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Challenges to agile project management during COVID-19 pandemic: an emerging economy perspective

Globally, COVID-19 pandemic has affected more than 214 countries across the world, creating uncertainty and affecting every institution and individual. The organisations recognise the need of agile projects that may offer several benefits including faster deployments, adaptability and best fit alignment to fulfill the customer needs. Implementing agile projects is the key to survive in the post pandemic situation, but emerging economies have limited scope for implementation. The present study determines the critical factors that restricts implementation of agile projects in emerging economies. The critical factors are identified from literature and validated by experts. The validated critical factors are further assessed to identify the cause-and-effect relationship using Fuzzy Decision-Making Trial and Laboratory (F-DEMATEL) method. The results of the study posit ‘Skepticism towards the new way of working’ is the most significant causal factor affecting other factors. This study is an attempt to help project managers to consider the significant factors for agile project implementation in post pandemic situation. The project managers may be benefitted from this study by considering these factors to manage challenges for agile project implementation in emerging economies. This study contributes to assess the influencing and the influenced challenging factors for agile project implementation.

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Arrhythmias in patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: Incidences and implications

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to impact populations around the globe. Information regarding the incidences and implications of arrhythmias in COVID-19 is limited. METHODS: A total of 463 patients with COVID-19 and who had at least one electrocardiogram recording from February 1 to March 19, 2020, in Wuhan Union Hospital were enrolled in the study. RESULTS: Arrhythmias occurred in 85 of 463 (18.4%) patients: atrial arrhythmias in 10.2%, junctional arrhythmias in 0.2%, ventricular arrhythmias in 3.5%, and conduction block in 7.3%. Compared with patients without arrhythmias, those with arrhythmias had higher mortality, both during the time from symptom onset (p < 0.001) and from admission to follow-up (p < 0.001). The frequencies of severe COVID-19 (44.7% vs. 21.2%; p < 0.001) and death (25.9% vs. 10.1%; p < 0.001) were higher in patients with arrhythmias than in those without arrhythmias. Atrial arrhythmias and ventricular arrhythmias could predict severity and mortality, their odds ratios (OR) were 4.45 (95% confidence interval [CI] 2.35 to 8.40), 5.80 (95% CI 1.89 to 17.76) respectively for severity, and were 3.51 (95% CI 1.74 to 7.08), 3.41 (95% CI 1.13 to 10.24) respectively for mortality. High levels of interleukin-6 (IL-6) and IL-10 were associated with the occurrence of arrhythmias (all p < 0.05). CONCLUSION: Arrhythmias were significantly associated with COVID-19 severity and mortality. Atrial arrhythmia was the most frequent arrhythmia type. IL-6 and IL-10 levels can predict the risk of arrhythmias in COVID-19 patients.

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Determinants of Face Mask Utilization to Prevent Covid-19 Pandemic among Quarantined Adults in Tigrai Region, Northern Ethiopia, 2020

A face mask is a vital component of personal protective equipment to prevent potentially contagious respiratory infections. There was a lack of evidence showing the proportion and determinants of face mask use in Ethiopia. Therefore, this study aimed to identify face mask utilization determinants to prevent spread of the Covid-19 pandemic among quarantined adults in Tigrai region, northern Ethiopia. A total of 331 participants selected using a systematic random sampling method were included in the study. An interviewer-administered questionnaire was employed. After describing the variables using frequencies, means, and standard deviations, multivariable logistic regression determined factors associated with face mask utilization to prevent COVID-19 spread. The study participants were primarily males (70%) and mean age was 30.5 (SD = 11) years. Nearly half of the participants reported they did not wear a face mask when leaving home. Face mask utilization was significantly associated with knowledge score, employment status, gender, age, and educational status of the study participants.

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Simplified and Improved Separations Between Regular and General Resolution by Lifting

We give a significantly simplified proof of the exponential separation between regular and general resolution of Alekhnovich et al. (2007) as a consequence of a general theorem lifting proof depth to regular proof length in resolution. This simpler proof then allows us to strengthen the separation further, and to construct families of theoretically very easy benchmarks that are surprisingly hard for SAT solvers in practice.

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The cleft palate candidate gene BAG6 supports FoxO1 acetylation to promote FasL-mediated apoptosis during palate fusion.

BACKGROUND Cleft palate is a common craniofacial defect, which occurs when the palate fails to fuse during development. During fusion, the palatal shelves migrate towards the embryonic midline to form a seam. Apoptotic elimination of medial edge epithelium (MEE) cells along this seam is required for the completion of palate fusion. METHODS Whole exome sequencing (WES) of six Chinese cleft palate families was applied to identify novel cleft palate-associated gene variants. Palatal fusion and immunofluorescence studies were performed in a murine palatal shelf organ culture model. Gene and protein expression were analyzed by qPCR and immunoblotting in murine MEE cells during seam formation in vivo. Mechanistic immunoprecipitation studies were performed in murine MEE cells in vitro. RESULTS WES identified Bcl-2 associated anthanogene 6 (BAG6) as a novel cleft palate-associated gene. In murine MEE cells, we discovered upregulation of Bag6 and the transcription factor forkhead box protein O1 (FoxO1) during seam formation in vivo. Using a palatal shelf organ culture model, we demonstrate that nuclear-localized Bag6 enhances MEE cell apoptosis by promoting p300's acetylation of FoxO1, thereby promoting transcription of the pro-apoptotic Fas ligand (FasL). Subsequent gain- and loss-of-function studies in the organ culture model demonstrated that FasL is required for Bag6/acFoxO1-mediated activation of pro-apoptotic Bax/caspase-3 signaling, MEE apoptosis, and palate fusion. Palatal shelf contact was shown to enhance Bag6 nuclear localization and upregulate nuclear acFoxO1 in MEE cells. CONCLUSIONS These findings demonstrate that nuclear-localized Bag6 and p300 co-operatively enhance FoxO1 acetylation to promote FasL-mediated MEE apoptosis during palate fusion.

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Application of Needleman-Wunch Algorithm to identify mutation in DNA sequences of Corona virus

—Corona virus is a virus capable of mutating very quickly and many other viruses that arise due to mutations of this virus. To find out the location of corona virus mutations of one type to another, DNA sequences can be aligned using the Needleman-Wunsch algorithm. Corona virus data was taken from Genbank National Center for Biotechnology Information from 1985-1992. The Needleman-Wunsch algorithm is a global alignment algorithm in which alignment is performed to all sequences with the complexity of O (mn) and is capable of producing optimal alignment. An important step in this reserach is the sequence alignment of two corona viruses using the Needleman-Wunsch algorithm. Second, identification of the location of mutations from the DNA of the virus. The result of this reserach is an alignment and the location of mutations of both sequences. The results of identification DNA mutation can be used to find out other viruses mutation corona virus as well as can be used in the field of health as a reference for the manufacture of drugs for corona virus mutation outcome.

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Comparison of novel stabilisation device with various stabilisation approaches: A finite element based biomechanical analysis

The treatment of spinal failure requires suitable instrumentation, which is based on numerous concepts such as rigid fixation, semi-rigid and dynamic stabilisation. In the present work, the biomechanical investigation of various fixation systems on the lumbar segment L2-L3 was performed employing finite element analysis. Different devices were considered: novel stabilisation device (NSD), rigid implant (RI) and existing dynamic stabilisation device (EDSD). All instrumented models were loaded with a condition of 400 N compressive force with a moment of 10Nm during flexion, extension, lateral bending and axial rotation. The results of range of motion change (RMC), von-Mises stress and strain were compared. The spinal biomechanics post instrumentation resulted significantly sensitive to the geometrical feature of the implant. The obtained results showed that NSD has intermediate motion characteristics in between dynamic stabilisation and rigid fixation. However, the optimum features of a novel stabilisation device for the treatment of spinal failure still need to be verified employing in-vivo, in-vitro studies.

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The promise of direct-to-consumer COVID-19 testing: ethical and regulatory issues

Widespread diagnostic and serological (antibody) testing is one key to mitigating the COVID-19 pandemic While at first, the majority of COVID-19 diagnostic testing in the USA took place in healthcare settings, quickly a direct-to-consumer (DTC) testing market also emerged In these DTC provision models, the test is initiated by a consumer and the sample collection occurs at home or in a commercial laboratory Although the provision of DTC tests has potential benefits—such as expanding access to testing and reducing the risk of exposure for consumers and medical personnel—it also raises significant ethical and regulatory concerns This article reviews these challenges and shows how they parallel and also diverge from prior concerns raised in the DTC health testing arena The first part of this paper provides an overview of the landscape of diagnostic and serological tests for COVID-19, anticipating how provision models are likely to evolve in the future The second part discusses five primary issues for DTC COVID-19 tests: test accuracy;potential misinterpretation of results;misleading claims and other misinformation;privacy concerns;and fair allocation of scarce resources We conclude with recommendations for regulators and companies that aim to ensure ethically marketed DTC COVID-19 tests

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Influenza season 2020–2021 did not begin in Finland despite the looser social restrictions during the second wave of COVID‐19: A nationwide register study

The nationwide lockdowns ended influenza seasons rapidly in Northern Hemisphere in Spring 2020. The strategy during the second wave was to minimize the restrictions set for children. Children spread influenza and therefore simultaneous influenza and COVID‐19 surges were feared. The aim of this report is to analyze the epidemiology of influenza season 2020–2021 in Finland. Data for this retrospective register‐based study were gathered from the National Infectious Disease Register, all laboratory‐confirmed influenza cases from August 2017 to March 2021 were included. The positive influenza findings were stratified by age, and incidences per 100 000 persons were calculated. Only 41 influenza A and B cases have been reported in this season from August 2020 to March 2021, which adds up to an incidence of 0.9 per 100 000 person‐years. In the three preceding years, the numbers and corresponding incidences from August to March were 12 461 (282 per 100 000 person‐years) in 2019–2020, 15 276 (346 per 100 000 person‐years) in 2018–2019, and 33 659 (761 per 100 000 person‐years) in 2017–2018. Nonpharmaceutical interventions combined with the lockdown measures interrupted the influenza season in Finland in March 2020. Despite looser restrictions, alongside traveling restrictions and facial masks, failing to prevent the spread of the severe acute respiratory syndrome coronavirus 2 virus, these restrictions have proved to be effective against seasonal influenza.

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Genetic and epigenetic analyses of panic disorder in the post-GWAS era

Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.

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Early phase of COVID-19 quarantine impacted insomnia symptoms in Turkish families

Quarantine and isolation are the most important public health measures used to prevent the transmission of infectious diseases among individuals. Quarantine and social isolation cause some health problems, such as depressive symptoms, sleep disturbances, anxiety, irritability, feeling of loneliness, helplessness, and trauma and post-traumatic stress symptoms. In this study, we aimed to examine early phase of COVID-19 quarantine impacted insomnia symptoms in Turkish families. The population of the study comprised students attending the Department of Healthcare Services of Eldivan Health Vocational School at Çankırı Karatekin University and their families. In total, 564 students and their families completed online surveys. Data was collected with Google forms. Snowball sampling was used as the data collection method. Female participants, those who gained weight during home quarantine, those who put their phones under their pillow or at the bedside and in another room, and those who used a phone or tablet before sleeping were found to have significantly more insomnia compared to others. The mean day of uninterrupted home quarantine was higher for participants experiencing insomnia (p<0.05). This study showed that individuals experienced sleep problems during the home quarantine.

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Essential role of STAT5a in DCIS formation and invasion following estrogen treatment

Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment of this pre-invasive disease could benefit from better understanding the pathways involved. While a decreased expression of Caveolin-1 (Cav-1) in the tumor microenvironment of patients with DCIS breast cancer was linked to progression to invasive breast cancer (IBC), the downstream effector(s) contributing to this process remain elusive. The current report shows elevated expression of Signal Transducer and Activator of Transcription 5a (STAT5a) within the DCIS-like lesions in Cav-1 KO mice following estrogen treatment and inhibition of STAT5a expression prevented the formation of these mammary lesions. In addition, STAT5a overexpression in a human DCIS cell line (MCF10DCIS.com) promoted their invasion, a process accelerated by estrogen treatment and associated with increased levels of the matrix metalloproteinase-9 (MMP-9) precursor. In sum, our results demonstrate a novel regulatory axis (Cav-1♦STAT5a♦MMP-9) in DCIS that is fully activated by the presence of estrogen. Our studies suggest to further study phosphorylated STAT5a (Y694) as a potential biomarker to guide and predict outcome of DCIS patient population.

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Epidemic Dynamics via Wavelet Theory and Machine Learning, with Applications to Covid-19

We introduce the concept of epidemic-fitted wavelets which comprise, in particular, as special cases the number $I(t)$ of infectious individuals at time $t$ in classical SIR models and their derivatives. We present a novel method for modelling epidemic dynamics by a model selection method using wavelet theory and, for its applications, machine learning based curve fitting techniques. Our universal models are functions that are finite linear combinations of epidemic-fitted wavelets. We apply our method by modelling and forecasting, based on the John Hopkins University dataset, the spread of the current Covid-19 (SARS-CoV-2) epidemic in France, Germany, Italy and the Czech Republic, as well as in the US federal states New York and Florida.

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Did the SARS-CoV-2 effect pregnancy complications?

OBJECTIVES This study aimed to evaluate the effect of SARS-CoV-2 on pregnancy complications, which increased compared to the same period before the pandemic. MATERIAL AND METHODS This prospective study was conducted at Etlik Zübeyde HanımWomen'sHealthPractices &Research Center between June 2020 and July 2020. The asymptomatic term PROM and miscarriage pregnant women were screened for SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) positivity by using IgM and IgG antibody tests. All the positive cases were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). All the patients answered 12 questions to determine their approach to COVID-19. RESULT Four of the 205 (2%) term PROM patients had positive anti-SARS-CoV-2 IgM antibody tests, one of the 205 (0.5%) term PROM patients had a positive anti-SARS-CoV-2 IgG antibody test, and one of the 205 (% 0.5) term PROM patients had positive anti-SARS-CoV-2 IgM and IgG antibody tests. All 230 miscarriage patients had negative IgM/IgG antibody tests. Four of the positive antibody cases had positive RT-PCR tests (2%) and were referred to a pandemic hospital. The patients thought that 93.2% and 95.6% of pregnant women with term PROM and miscarriage, respectively, SARS-CoV-2 would infect themselves, and 89.8% and 92.6%, respectively, would infect their children. The number of patients who would not consider pregnancy if they were not pregnant during this period was significantly higher in the term PROM (48.3%) compared to the miscarriage (27.8%) patients (p < 0.005). CONCLUSIONS No COVID-19 cases were determined in the asymptomatic miscarriage patients. In the asymptomatic term PROM patients, the effects of COVID were not observed.

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Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection

Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses.

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Mechanisms and consequences of COVID-19 associated liver injury: What can we affirm?

Since the first reports of coronavirus disease 2019 (COVID-19) cases in December 2019 in China, numerous papers have been published describing a high frequency of liver injury associated with severe acute respiratory syndrome coronavirus 2 infection, many of them proposing a link between these findings and patient outcomes. Increases in serum aminotransferase levels (ranging from 16% to 62%) and bilirubin levels (ranging from 5% to 21%) have been reported and seem to be more often observed in patients with severe forms of COVID-19. Although absolute changes in these parameters are frequently seen, other variables, such as the ratio above the upper limit of normal, the onset of liver injury as a complication in severe cases and histopathological findings, reinforce that liver changes are of dubious clinical relevance in the course of this disease. Other factors must also be considered in these analyses, such as the repercussions of hemodynamic changes, the presence of thrombotic events, and, mainly, the possible drug-induced liver injury with the current, yet off-label, treatment. This paper aimed to analyze the currently available data on liver injury in patients with COVID-19.

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Can pulse steroid therapy increase the risk of infection by COVID-19 in patients with multiple sclerosis?

BACKGROUND: Iran is one of the countries with a high prevalence of multiple sclerosis (MS) and COVID-19.MS patients receiving the immunomodulatory or immunosuppressive therapy have a higher risk of infection. Due to the significance of determining the risk factors for getting COVID-19 among MS patients, the present study was designed to assess the risk of infection following the pulse steroid therapy. METHODS: This cross-sectional study included all MS patients that received corticosteroids in Tehran from December 2019 to August 2020 during the COVID-19 pandemic spread. The subjects’ clinical records including their sex, age, the type of MS, the type of medication, the number of days using corticosteroids, the status of prednisolone intake, and the number of days receiving prednisolone after the corticosteroid therapy were obtained. Moreover, main outcomes such as COVID-19 infection and the occurrence of death were recorded by patient’s visits and follow-up phone calls. COVID-19 infection was confirmed by physicians according to the clinical performance of RT-PCR, chest CT scan, and antibody tests. RESULTS: Totally, 133 MS cases participated in the study, and the pulse therapy was completed for 104 (78.2%) patients up to 5−7 days. 89 (66.9%) cases used the prednisolone tablet following the pulse therapy. Overall, the infection by Covid-19 was observed in 8 (6%) cases, among whom 5 (71.4%) cases received the pulse therapy for 5−7 days and 4 (57.1%) cases had a history of taking the prednisolone tablet. The age of less than 40 years (OR = 1.03; 95% CI (0.23−4.51)), male sex (OR = 0.35; 95% CI (0.03−3.34)), and the RRMS type (OR = 2.87; 95% CI (0.52−15.72)) had no effect on the risk of Covid-19 infection. In addition, there was not statistically significant difference between subjects with the short-term pulse therapy duration (3−4 days) (OR 0.68 (0.12–3.74) and those with the long-term pulse therapy duration (5−7 days). Similarly, no statistically significant difference was observed between subjects taking prednisolone (OR = 1.62 (0.34–7.61) and those not taking prednisolone. Furthermore, there was no significant association between different medication groups and the risk of Covid-19 infection (p < 0.05). No death occurred due to Covid-19 infection among the subjects. CONCLUSION: COVID-19 infection was more common among female and younger patients as well as patients with a longer duration of the pulse therapy and prednisolone intake. There was no significant association between the pulse steroid therapy in MS patients and the risk of infection by COVID-19 in the Iranian population.

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Correction: Inhibition of NLRP3 inflammasome activation and pyroptosis with the ethyl acetate fraction of Bungeanum ameliorated cognitive dysfunction in aged mice

Correction for 'Inhibition of NLRP3 inflammasome activation and pyroptosis with the ethyl acetate fraction of Bungeanum ameliorated cognitive dysfunction in aged mice' by Meihuan Zhao et al., Food Funct., 2021, DOI: 10.1039/D1FO00876E.

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