bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association meta-analysis supports genes involved in valve and cardiac development to associate with mitral valve prolapse
Authors: Yu Mengyao , Kyryachenko Sergiy , Debette Stephanie , Amouyel Philippe , Schott Jean-Jacques , Tourneau Thierry Le , Dina Christian , Norris Russell A , Hagège Albert A. , Jeunemaitre Xavier , Bouatia-Naji Nabila 
Published: July 2020

AbstractObjectiveMitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous GWAS have identified six risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding a dataset from the UK Biobank.Approaches and ResultsWe re-analyzed 1,007/1,469 cases and 479/862 controls from the MVP-France study and the MVP-Nantes study, respectively. We re-imputed genotypes using HRC and TOPMed, and found this latter to perform better in terms of accuracy in the lower ranges of minor allele frequency (MAF) below 0.1. We then incorporated 434 MVP cases and 4,527 controls from the UKBiobank and conducted a meta-analysis GWAS including ∼2000 MVP cases and over 6,800 controls for ∼8 million genotyped or imputed common SNPs (MAF>0.01). We replicated the association on chr2 and now provide a finer association map nearTNS1. We identified three suggestive risk loci, all driven by common variants on Chr1 (SYT2), Chr8 (MSRA), and Chr19 (FBXO46). Gene-based association using MAGMA revealed 15 risk genes for MVP includingGLIS1, TGFB2, ID2, TBX5, MSRA, andDMPK. Extensive functional annotation showed that genes associated with MVP are highly expressed in cardiovascular tissues, especially heart, and are involved in cardiac development and potentially aging.ConclusionsWe report an updated meta-analysis GWAS for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.TOC category - basic and population studiesTOC subcategory - Arteriosclerosis, Thrombosis, and Vascular BiologyHighlightsProvide high coverage meta-analysis of GWAS based on TOPMed imputation involving ∼8 million common variants in ∼2000 MVP patients and ∼6800 controls.Low frequency variant contributed little to the association of the genes mentioned, where the associations were driven by common variantsSeveral association loci involve genes related to cardiac development and potentially aging.
Exposure assessment for airborne transmission of SARS-CoV-2 via breathing, speaking, coughing and sneezing
Authors: Schijven Jack , Vermeulen Lucie C. , Swart Arno , Meijer Adam , Duizer Erwin , de Roda Husman Ana Maria 
Published: July 2020

AbstractBackgroundEvidence for indoor airborne transmission of SARS-CoV-2 is accumulating. If SARS-CoV-2 also spreads via aerosols, this has implications for measures taken to limit transmission.ObjectivesThe aim of this study is to assess exposure to airborne SARS-CoV-2 particles from breathing, speaking, coughing and sneezing in an indoor environment.MethodsAn exposure assessment model was developed to estimate numbers of SARS-CoV-2 particles in aerosol droplets, expelled during breathing, speaking, coughing and sneezing by an infected person in an unventilated indoor environment, and subsequent inhalation by one or more persons. Scenarios encompass a range of virus concentrations, room sizes and exposure times.ResultsThe calculated total volume of expelled aerosol droplets was highest for a sneeze, followed by a cough and speaking for 20 minutes, and lastly breathing for 20 minutes. A few to as much as tens of millions of virus particles were expelled. Exposure probability strongly depends on the viral concentration in mucus, as well as on the scenario. Exposure probabilities were generally below 1% at a virus concentration in mucus below 105 per mL for all scenarios, increasing steeply at different higher concentrations. According to nose / throat swab data collected from patients, 75%, 50% and 5% of infected individuals carry an estimated number of SARS-CoV-2 per mL mucus of at least 105, 106 and 108, respectively.DiscussionExposure to SARS-CoV-2 via aerosols generated during breathing, speaking, coughing and sneezing in an unventilated indoor environment is possible. This study forms a basis to estimate probabilities of exposure to SARS-Cov-2 by airborne transmission in indoor spaces. As long as it is uncertain what fraction of the airborne virus particles is infectious and as long as a dose response relation is lacking, it is recommended to be precautious.
The reproduction number R for COVID-19 in England: Why hasn’t “lockdown” been more effective?
Authors: Grant Alastair 
Published: July 2020

AbstractThe reproduction number R, the average number of people that a single individual with a contagious disease infects, is central to understanding the dynamics of the COVID-19 epidemic. Values greater than one correspond to increasing rates of infection, and values less than one indicate that control measures are being effective. Here, we summarise how changes in the behaviour of individuals alter the value of R. We also use matrix models that correctly recreate distributions of times that individuals spend incubating the disease and being infective to demonstrate the accuracy of a simple approximation to estimate R directly from time series of case numbers, hospital admissions or deaths. The largest uncertainty is that the generation time of the infection is not precisely known, but this challenge also affects most of the more complex methods of calculating R. We use this approximation to examine changes in R in response to the introduction of “lockdown” restrictions in England. This suggests that there was a substantial reduction in R before large scale compulsory restrictions on economic and social activity were imposed on 23rd March 2020. From mid-April to mid-June decline of the epidemic at national and regional level has been relatively slow, despite these restrictions (R values clustered around 0.81). However, these estimates of R are consistent with the relatively high average numbers of close contacts reported by confirmed cases combined with directly measured attack rates via close interactions. This implies that a significant portion of transmission is occurring in workplaces; overcrowded housing or through close contacts that are not currently lawful, routes on which nationwide lockdown will have limited impact.
Clinical Characteristics of Recurrent-positive Coronavirus Disease 2019 after Curative Discharge: a retrospective analysis of 15 cases in Wuhan China
Authors: Chen Lan , Zhang Zhen-Yu , Zhang Xiao-Bin , Zhang Su-Zhen , Han Qiu-Ying , Feng Zhi-Peng , Fu Jian-Guo , Xiao Xiong , Chen Hui-Min , Liu Li-Long , Chen Xian-Li , Lan Yu-Pei , Zhong De-Jin , Hu Lan , Wang Jun-Hui , Yin Zhen-Yu 
Published: July 2020

AbstractIn China, the patients with previously negative RT-PCR results again test positive during the post-discharge isolation period. We aimed to determine the clinical characteristics of these “recurrent-positive” patients. We retrospectively reviewed the data of 15 recurrent-positive patients and 107 control patients with non-recurrent, moderate COVID-19 treated in Wuhan, China. Clinical data and laboratory results were comparatively analyzed. We found that recurrent-positive patients had moderate disease. The rate of recurrent-positive disease in our hospital was 1.87%. Recurrent-positive patients were significantly younger (43(35-54) years) than control patients (60(43-69) years) (P=0.011). The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive patients (36(34-45) days) than in control patients (15(7-30) days) (P =0.001). The time required for the first conversion of RT-PCR results from positive to negative was significantly longer in recurrent-positive patients (14(10-17) days) than in control patients (6(3-9) days) (P =0.011). Serum COVID-19 antibody levels were significantly lower in recurrent-positive patients than in control patients (IgM: 13.69 ± 4.38 vs. 68.10 ± 20.85 AU/mL, P = 0.015; IgG: 78.53 ± 9.30 vs. 147.85 ± 13.33 AU/mL, P < 0.0001). Recurrent-positive patients were younger than control patients. The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive group than that in control group. COVID-19 IgM/IgG antibody levels were significantly lower in recurrent-positive group than those in control group, which might explain why the virus RNA RT-PCR was positive after the initial “clinical cure”(with three times of virus RNA RT-PCR negative). The virus might not be fully eliminated because of the lower IgG level and their later replicating might result in recurrent-positive virus RNA RT-PCR.
Curve-fitting approach for COVID-19 data and its physical background
Authors: Nishimoto Yoshiro , Inoue Kenichi 
Published: July 2020

AbstractForecast of the peak-out and settling timing of COVID-19 at an early stage should help the people how to cope with the situation. Curve-fitting method with an asymmetric log-normal function has been applied to daily confirmed cases data in various countries. Most of the curve-fitting could show good forecasts, while the reason has not been clearly shown. The K value has recently been proposed which can provide good reasoning of curve-fitting mechanism by corresponding a long and steep slope on the K curve with fitting stability. Since K can be expressed by a time differential of logarithmic total cases, the physical background of the above correspondence was discussed in terms of the growth rate in epidemic entropy.
Prediction of COVID-19 Active and Total Cases After a Fall and Rise of Cases
Authors: Viswanath Narayanan C. 
Published: July 2020

AbstractDuring the progress of the COVID-19, many countries have observed that their active cases tend to rise again after falling for some time. This may cause some mathematical models like the one discussed in [2] tend to make errors in the future prediction. We discuss a simple method to better the future prediction in such cases. This method is applied on the active and total cases data for the countries USA and Canada. In the case of Canada, the method succeeded in predicting the date when the active cases began to decrease. In the case of USA, a major improvement in prediction was observed when the method was applied: the predicted active and total cases are 1465602 and 2729015 for June 30; whereas the actual values are 1455400 and 2728856. We also give the active and total cases prediction for Canada and the USA for the first week of July 2020.
Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes
Authors: Zacharioudakis Ioannis M. , Prasad Prithiv J. , Zervou Fainareti N. , Basu Atreyee , Inglima Kenneth , Weisenberg Scott A. , Aguero-Rosenfeld Maria E. 
Published: July 2020

AbstractRationaleThe Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.ObjectivesWe explored the SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.MethodsA retrospective cohort study among adult patients admitted to the hospital between March 31st to April 10th, 2020 with COVID-19 pneumonia was conducted. We segregated patients into 3 genomic load groups: low (Cycle threshold (Ct) ≥35), intermediate (25<Ct<35), and high (Ct≤ 25) using real-time polymerase chain reaction.MeasurementsA composite outcome of death, intubation, and/or extracorporeal membrane oxygenation was used. Secondary outcomes included the severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI).Main ResultsOf 457 patients with COVID-19 pneumonia from March 31st to April 10th, 2020, 316 met inclusion criteria. Included patients were followed for a median of 25days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index (p=0.005), transplant recipient status (p<0.001), and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, a high genomic load remained an independent predictor of the primary outcome. Results remained significant in sensitivity analyses.ConclusionsOur findings suggest that a high genomic load of SARS-CoV-2 at the time of admission is an independent predictor of adverse outcomes, that above and beyond age, comorbidity, and severity of illness on presentation, may be used to risk-stratify patients, and call for a quantitative diagnostic assay to become available.
Assessing the burden of COVID-19 amongst healthcare workers in Mexico City: A data-driven call to action
Authors: Antonio-Villa Neftali Eduardo , Bello-Chavolla Omar Yaxmehen , Vargas-Vázquez Arsenio , Fermín-Martínez Carlos A. , Márquez-Salinas Alejandro , Pisanty-Alatorre Julio , Bahena-López Jessica Paola 
Published: July 2020

ABSTRACTBACKGROUNDHealth-care workers (HCWs) could be at increased occupational risk for SARS-CoV-2 infection due to increased exposure. Information regarding the burden of COVID-19 epidemic in HCWs living in Mexico is scarce. Here, we aimed to explore the epidemiology, symptoms, and risk factors associated with adverse outcomes in HCWs in Mexico City.METHODSWe explored data collected by the National Epidemiological Surveillance System in Mexico City, in HCWs who underwent real-time RT-PCR test. We explored COVID-19 outcomes in HCWs and the performance of symptoms to detect SARS-CoV-2 infection.RESULTSAs of September 20th, 2020, 57,758 HCWs were tested for SARS-CoV-2 and 17,531 were confirmed (30.35%); 6,610 were nurses (37.70%), 4,910 physicians (28.0%), 267 dentists (1.52%) and 5,744 laboratory personnel and other HCWs (32.76%). Overall, 2,378 HCWs required hospitalization (4.12%), 2,648 developed severe COVID-19 (4.58%), and 336 required mechanical-ventilatory support (0.58%). Lethality was recorded in 472 (0.82%) cases. We identified 635 asymptomatic SARS-CoV-2 infections (3.62%). Compared with general population, HCWs had higher incidence, testing, asymptomatic and mortality rates. No individual symptom offers adequate performance to detect SARS-CoV2. Older HCWs with chronic non-communicable diseases and severe respiratory symptoms were associated with higher risk for adverse outcome; physicians were at higher risk compared with nurses and other HCWs.CONCLUSIONSWe report a high prevalence of SARS-CoV-2 infection in HCWs in Mexico City. Symptoms as a screening method is not efficient to discern those HCWs with a positive PCR-RT test. Particular attention should focus on HCWs with risk factors to prevent adverse outcomes.
Association of Sickle Cell Trait with Risk and Mortality of COVID-19: Results from the UK Biobank
Authors: Resurreccion W. Kyle , Shi Zhuqing , Wei Jun , Na Rong , Zheng S. Lilly , Hulsizer Joseph , Struve Clay , Helfand Brian T. , Khandekar Janardan , Caplan Michael S. , Xu Jianfeng 
Published: July 2020

AbstractWe tested the hypothesis that patients with sickle cell trait (SCT), a common condition in individuals of African descent, have increased risk and mortality for coronavirus disease (COVID-19) in the UK Biobank. By June 17, 2020, 1,550 of 7,668 (20%) tested subjects were positive for COVID-19, including 298 (19%) deaths. Blacks had higher rates than Whites for COVID-19 infections (79/222=36% vs. 1,342/7,010=19%,P=1.28×10−9). Among Blacks, SCT carriers did not have higher infection rates (5/15=33%) than non-SCT carriers (74/207=36%),P=1.00. However, SCT carriers had a trend of higher death rates (2/5=40%) than non-SCT carriers (12/74=16%), although not statistically significant (P=0.21).
Early COVID-19 Interventions Failed to Replicate 1918 St. Louis vs. Philadelphia Outcomes in the United States
Authors: Jalali Aliea M. , Peterson Brent M. , Galbadage Thushara 
Published: July 2020

ABSTRACTThe Coronavirus disease 2019 (COVID-19) pandemic has elicited an abrupt pause in the United States in multiple sectors of commerce and social activity. As the US faces this health crisis, the magnitude, and rigor of their initial public health response was unprecedented. As a response, the entire nation shutdown at the state-level for the duration of approximately one to three months. These public health interventions, however, were not arbitrarily decided, but rather, implemented as a result of evidence-based practices. These practices were a result of lessons learned during the 1918 influenza pandemic and the city-level non-pharmaceutical interventions (NPIs) taken across the US. During the 1918 pandemic, two model cities, St. Louis, MO, and Philadelphia, PA, carried out two different approaches to address the spreading disease, which resulted in two distinctly different outcomes. Our group has evaluated the state-level public health response adopted by states across the US, with a focus on New York, California, Florida, and Texas, and compared the effectiveness of reducing the spread of COVID-19. Our assessments show that while the states mentioned above benefited from the implementations of early preventative measures, they inadequately replicated the desired outcomes observed in St. Louis during the 1918 crisis. Our study indicates that there are other factors, including health disparities that may influence the effectiveness of public health interventions applied. Identifying more specific health determinants may help implement targeted interventions aimed at preventing the spread of COVID-19 and improving health equity.
COVID-19 associated anxiety enhances tinnitus
Authors: Xia Li , He Gang , Feng Yong , Yu Xiaoxu , Zhao Xiaolong , Chen Zhengnong , Yin Shankai , Wang Jian , Fan Jiangang , Dong Chuan 
Published: July 2020

AbstractObjectivesTo investigate if the anxiety associated with COVID-19 is a promoting factor to tinnitus.MethodsA retrospective research design was used to compare the clinical characteristics of tinnitus between the patients in 2020 under pandemic pressure and those from the matching period in 2019. While anxiety was quantified using the Zung’s Self-rating Anxiety Scale (SAS), tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) questionnaire and the test of minimum masking level (MML). The assessments were repeated after the sound therapy plus educational counselling (STEC) and compared with EC alone therapy.ResultsA large increase in anxiety was evident in 2020 in both case rate and SAS. The treatment of both methods was less effective in 2020. SAS, THI and MML were all deteriorated after the EC alone treatment in 2020, while an improvement was seen in 2019. This suggests that EC alone could not counteract the stress by COVID-19 at all, and the stress, if not managed well, can significantly increase the severity of tinnitus and associated anxiety.ConclusionsBy using the EC subgroup in virtual control, we conclude that anxiety can serve as a promoting factor to tinnitus. We believe that this is the first study report that confirm the causative/promotive role of anxiety on tinnitus.
The potential role of miR-21-3p in coronavirus-host interplay
Authors: Nersisyan Stepan , Engibaryan Narek , Gorbonos Aleksandra , Kirdey Ksenia , Makhonin Alexey , Tonevitsky Alexander 
Published: July 2020

ABSTRACTHost miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses by several possible mechanisms including direct binding the viral RNA. Identification of human miRNAs involved in coronavirus-host interplay is becoming important due to the ongoing COVID-19 pandemic. In this work we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. In order to uncover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV. Further bioinformatic analysis of binding sites revealed high conservativity of miR-21-3p binding regions within RNAs of human coronaviruses and their strains.
BAZ2A association with H3K14ac is required for the transition of prostate cancer cells into a cancer stem-like state
Authors: Peña-Hernández Rodrigo , Aprigliano Rossana , Frommel Sandra , Pietrzak Karolina , Steiger Seraina , Roganowicz Marcin , Bizzarro Juliana , Santoro Raffaella 
Published: July 2020

AbstractProstate cancer (PCa) is one of the most prevalent cancers in men. Cancer stem cells are thought to be associated with PCa relapse. Here we show that BAZ2A is required for the transition of PCa cells into a cancer stem-like state. BAZ2A genomic occupancy in PCa cells coincides with H3K14ac enriched chromatin regions. This association is mediated by BAZ2A-bromodomain (BAZ2A-BRD) that specifically binds H3K14ac. BAZ2A associates with inactive enhancers marked by H3K14ac and repressing transcription of genes frequently silenced in aggressive and poorly differentiated PCa. BAZ2A-mediated repression is also linked to EP300 that acetylates H3K14ac. BAZ2A-BRD mutations or treatment with inhibitors abrogating BAZ2A-BRD/H3K14ac interaction impair the transition of PCa cells into a stem-like state. Furthermore, pharmacological inactivation of BAZ2A-BRD impairsPten-loss oncogenic transformation of prostate organoids. Our findings indicate a role of BAZ2A-BRD in PCa stem cell features and suggest potential epigenetic-reader therapeutic strategies to target BAZ2A in aggressive PCa.
Red-light is an environmental effector for mutualism between begomovirus and its vector whitefly
Authors: Zhao Pingzhi , Zhang Xuan , Gong Yuqing , Xu Dongqing , Wang Ning , Sun Yanwei , Liu Shu-Sheng , Deng Xing-Wang , Kliebenstein Daniel J. , Zhou XuePing , Fang Rong-Xiang , Ye Jian 
Published: July 2020

AbstractEnvironments such as light condition influence the spread of infectious diseases by affecting insect vector behavior. However, whether and how light affects the host defense which further affect insect preference and performance, remains unclear, nor has been demonstrated how pathogens co-adapt light condition to facilitate vector transmission. We previously showed that begomoviral βC1 inhibits MYC2-mediated jasmonate signaling to establish plant-dependent mutualism with its insect vector. Here we show red-light as an environmental catalyzer to promote mutualism of whitefly-begomovirus by stabilizing βC1, which interacts with PHYTOCHROME-INTERACTING FACTORS (PIFs) transcription factors. PIFs positively control plant defenses against whitefly by directly binding to the promoter of terpene synthase genes and promoting their transcription. Moreover, PIFs integrates light and jasmonate signaling by interaction with MYC2, and co-regulation the transcription of terpene synthase genes. However, begomovirus encoded βC1 inhibit PIFs’ and MYC2’ transcriptional activity via disturbing their dimerization, thereby impairing plant defenses against whitefly-transmitted begomoviruses. Our results thus describe how a viral pathogen hijacks host light signaling to enhance the mutualistic relationship with its insect vector.Author summaryClimate change is driving disease rapidly spread, esp. for global distribution of insect-borne diseases. This paper reports red-light as an environmental factor to promote insect vector olfactory orientation behavior and increase viral disease transmission. Plant virus adapts the supplemental red lighting practice in modern agricultural greenhouse production under protection, therefore enhancing disease spreading globally.