bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and ethnic determinants of Covid-19 risk
Authors: Lo Chun-Han , Nguyen Long H. , Drew David A. , Graham Mark S. , Warner Erica T. , Joshi Amit D. , Astley Christina M. , Guo Chuan-Guo , Ma Wenjie , Mehta Raaj S. , Kwon Sohee , Song Mingyang , Davies Richard , Capdevila Joan , Lee Karla A. , Lochlainn Mary Ni , Varsavsky Thomas , Sudre Carole H. , Wolf Jonathan , Cozier Yvette C. , Rosenberg Lynn , Wilkens Lynne R. , Haiman Christopher A. , Le Marchand Loïc , Palmer Julie R. , Spector Tim D. , Ourselin Sebastien , Steves Claire J. , Chan Andrew T. 
Published: June 2020

ABSTRACTBackgroundRacial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk.MethodsWe used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups.ResultsWe documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups.ConclusionsOur results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.
Design and clinical validation of a 3D-printed nasopharyngeal swab for COVID-19 testing
Authors: Tay Joshua K , Cross Gail B , Lee Chun Kiat , Yan Benedict , Loh Jerold , Lim Zhen Yu , Ngiam Nicholas , Chee Jeremy , Gan Soo Wah , Saraf Anmol , Eason Chow Wai Tung , Goh Han Lee , Siow Chor Hiang , Lian Derrick WQ , Loh Woei Shyang , Loh Kwok Seng , Chow Vincent TK , Wang De Yun , Fuh Jerry YH , Yen Ching-Chiuan , Wong John EL , Allen David M 
Published: June 2020

AbstractWe describe the development and validation of a novel 3D-printed nasopharyngeal swab for the identification of SARS-CoV-2. We subjected the novel swab to mechanical and fluid absorption testing ex-vivo, and confirmed its ability to retain and release murine coronavirus and SARS-CoV-2. Compared to the Copan FLOQSwab, the novel swab displayed excellent correlation of RT-PCR cycle threshold values on paired clinical testing in COVID-19 patients, at r = 0.918 and 0.943 for the SARS-CoV-2 ORF1/a and sarbecovirus E-gene respectively. Overall positive and negative percent agreement was 90.6% and 100% respectively on a dual-assay RT-PCR platform, with discordant samples observed only at high cycle thresholds. When carefully designed and tested, 3D-printed swabs are a viable alternative to traditional swabs and will help mitigate strained resources in the escalating COVID-19 pandemic.
Epidemiological description and analysis of RdRp, E and N genes dynamic by RT-PCR of SARS-CoV-2 in Moroccan population: Experience of the National Reference Laboratory (LNR)-UM6SS
Authors: Benrahma Houda , Idrissa Diawara , Imane Smyej , Jalila Rahoui , Nida Meskaouni , Rachid Benmessaoud , Khadija Arouro , Khadija Jaras , Zahra Moujid Fatima , Zahra Adam , Salma Nahir , Zineb Aouzal , Hajar Elguezzar , Leila Jeddane , Fadoua Ousti , Jalila EL Bakkouri , Chakib Nejjari 
Published: June 2020

AbstractThe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019. On 2 March 2020, the Moroccan Ministry of Health confirmed the first COVID-19 case in Morocco. The new virus SARS-CoV-2 was identified in the sample of a Moroccan expatriate residing in Italy. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus.This study aims to analyze the epidemiological profile of the SARS-CoV-2 in Moroccan cases and to investigate the dynamic of RdRp, N, and E genes in patients from diagnosis until the recovery.Among 859 COVID-19 RT-PCR tests realized for 376 patients, 187 cases had positive results COVID-19. 4% were positive with the 3 genes RdRp, N, and E, 40 % with N and E genes, 3% with RdRp and N genes, 31% with only the RdRp gene and 22% cases are positives with N gene. The analysis of the Covid-19 genes (RdRp, N, and E) dynamic reveal that more than 6% stay positive with detection of the N and E gene, and 14% with the N gene after 12 days of treatment.The median period from positive to the first negative Covid-19 RT-PCR tests was 6.8±2.24 days for 44% cases, 14.31± 2.4 days for 30%, and 22.67 ± 1.21 days for 4%.This a first description of the Moroccan COVID-19 cases and the analysis of the dynamic of the RdRp, N, and E genes. The analysis of our population can help to improve in the care of patients.
Cell lines of the same anatomic site and histologic type show large variability in radiosensitivity and relative biological effectiveness to protons and carbon ions
Authors: Flint David B. , Bright Scott J. , McFadden Conor H. , Konishi Teruaki , Ohsawa Daisuke , Turner Broderick , Lin Steven H. , Grosshans David R. , Shaitelman Simona F. , Chiu Hua-Sheng , Sumazin Pavel , Sawakuchi Gabriel O. 
Published: June 2020

AbstractPurposeTo show that radiation response across cancer cell lines of the same anatomic site and histologic type varies remarkably for protons and carbon (C) ions.Materials and MethodsWe measured and obtained from the literature clonogenic survival of human cancer cell lines of the lung (n=18), brain (n=10) and pancreas (n=10) exposed to photons, protons, and C-ions to assess their variability in response. We also treated cancer cell lines with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability in response. We quantified the variability in response by calculating the relative range (range/mean) and the coefficient of variation (COV) of the dose at 10% survival fraction (D10%) and relative biological effectiveness (RBE10%).ResultsThe relative range of D10%for lung cancer cell lines varied from 55-92% for photons, protons, and C-ions, with the relative range in RBE varying from 16-45% for protons and C-ions. For brain and pancreatic cancer cell lines, the relative range of D10%varied from 95-112%, and 39-75%, respectively, with the relative range in RBE varying from 27-33% and 25-50%, respectively. However, the COVs in D10%were approximately equal across radiation qualities, varying from 0.24±0.07–0.35±0.10, 0.35±0.09–0.69±0.62 and 0.13±0.03– 0.21±0.04 for lung, brain and pancreatic cancer cell lines, respectively. Greater relative ranges in D10%were observed in the cell lines with inhibited DNA repair, varying from 108%-157% for photons, protons, and C-ions, with relative ranges in RBE varying from 29-67%. The COVs in the D10%were also greater for the cell lines treated with inhibitors of DNA repair, varying from 0.34±0.09–0.41±0.06.ConclusionCell lines of the same anatomic site and histologic type have a remarkable variability in response, not only to photons but also to protons and C-ions. We attributed this variability to differences in DNA repair capacity.CategoryBiological Physics and Response Prediction
Repeatability and reproducibility of thewziHigh Resolution Melting-based clustering analysis forKlebsiella pneumoniaetyping
Authors: Pasala Ajay Ratan , Perini Matteo , Piazza Aurora , Panelli Simona , Di Carlo Domenico , Loretelli Cristian , Cafiso Alessandra , Inglese Sonia , Zuccotti Gian Vincenzo , Comandatore Francesco 
Published: June 2020

AbstractAimsHigh Resolution Melting (HRM) is a fast closed-tube method for nucleotide variant scanning applicable for bacterial species identification or molecular typing. Recently a novel HRM-based method forKlebsiella pneumoniaetyping has been proposed: it consists of an HRM protocol designed on the capsularwzigene and an HRM-based algorithm of strains clustering. In this study, we evaluated the repeatability and reproducibility of this method.Methods and ResultsWe performed HRM typing of a set ofK. pneumoniaestrains, on three different instruments and by two different operators. The results showed that operators do not affect measured melting temperatures while different instruments can. Despite this, we found that strains clustering analysis remains perfectly consistent performing the analysis using the MeltingPlot tool separately on the data from the three instruments.ConclusionsThe HRM protocol under study was highly repeatable and thus reliable for large studies, even when several operators are involved.Significance and Impact of the StudyOur results show that thewzi-HRM protocol forK. pneumoniaetyping is suitable for multicenter studies, even if different instruments are used.
Computationally efficient whole genome regression for quantitative and binary traits
Authors: Mbatchou Joelle , Barnard Leland , Backman Joshua , Marcketta Anthony , Kosmicki Jack A. , Ziyatdinov Andrey , Benner Christian , O’Dushlaine Colm , Barber Mathew , Boutkov Boris , Habegger Lukas , Ferreira Manuel , Baras Aris , Reid Jeffrey , Abecasis Gonçalo , Maxwell Evan , Marchini Jonathan 
Published: June 2020

AbstractGenome-wide association analysis of cohorts with thousands of phenotypes is computationally expensive, particularly when accounting for sample relatedness or population structure. Here we present a novel machine learning method called REGENIE for fitting a whole genome regression model that is orders of magnitude faster than alternatives, while maintaining statistical efficiency. The method naturally accommodates parallel analysis of multiple phenotypes, and only requires local segments of the genotype matrix to be loaded in memory, in contrast to existing alternatives which must load genomewide matrices into memory. This results in substantial savings in compute time and memory usage. The method is applicable to both quantitative and binary phenotypes, including rare variant analysis of binary traits with unbalanced case-control ratios where we introduce a fast, approximate Firth logistic regression test. The method is ideally suited to take advantage of distributed computing frameworks. We demonstrate the accuracy and computational benefits of this approach compared to several existing methods using quantitative and binary traits from the UK Biobank dataset with up to 407,746 individuals.
The enzymatic activity of the nsp14 exoribonuclease is critical for replication of Middle East respiratory syndrome-coronavirus
Authors: Ogando Natacha S. , Zevenhoven-Dobbe Jessika C. , Posthuma Clara C. , Snijder Eric J. 
Published: June 2020

AbstractCoronaviruses (CoVs) stand out for their large RNA genome and complex RNA-synthesizing machinery comprising 16 nonstructural proteins (nsps). The bifunctional nsp14 contains an N-terminal 3’-to-5’ exoribonuclease (ExoN) and a C-terminal N7-methyltransferase (N7-MTase) domain. While the latter presumably operates during viral mRNA capping, ExoN is thought to mediate proofreading during genome replication. In line with such a role, ExoN-knockout mutants of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) were previously found to have a crippled but viable hypermutation phenotype. Remarkably, using an identical reverse genetics approach, an extensive mutagenesis study revealed the corresponding ExoN-knockout mutants of another betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), to be non-viable. This is in agreement with observations previously made for alpha- and gammacoronaviruses. Only a single MERS-CoV ExoN active site mutant could be recovered, likely because the introduced D191E substitution is highly conservative in nature. For 11 other MERS-CoV ExoN active site mutants, not a trace of RNA synthesis could be detected, unless – in some cases – reversion had first occurred. Subsequently, we expressed and purified recombinant MERS-CoV nsp14 and establishedin vitroassays for both its ExoN and N7-MTase activities. All ExoN knockout mutations that were lethal when tested via reverse genetics were found to severely decrease ExoN activity, while not affecting N7-MTase activity. Our study thus reveals an additional function for MERS-CoV nsp14 ExoN, which apparently is critical for primary viral RNA synthesis, thus differentiating it from the proofreading activity thought to boost long-term replication fidelity in MHV and SARS-CoV.ImportanceThe bifunctional nsp14 subunit of the coronavirus replicase contains 3’-to-5’ exoribonuclease (ExoN) and N7-methyltransferase (N7-MTase) domains. For the betacoronaviruses MHV and SARS-CoV, the ExoN domain was reported to promote the fidelity of genome replication, presumably by mediating some form of proofreading. For these viruses, ExoN knockout mutants are alive while displaying an increased mutation frequency. Strikingly, we now established that the equivalent knockout mutants of MERS-CoV ExoN are non-viable and completely deficient in RNA synthesis, thus revealing an additional and more critical function of ExoN in coronavirus replication. Both enzymatic activities of (recombinant) MERS-CoV nsp14 were evaluated using newly developedin vitroassays that can be used to characterize these key replicative enzymes in more detail and explore their potential as target for antiviral drug development.
Clinical practice guidelines and recommendations in the context of the COVID-19 pandemic: systematic review and critical appraisal
Authors: Stamm Tanja A , Andrews Margaret R , Mosor Erika , Ritschl Valentin , Li Linda C , Ma Jasmin K , Arias Adalberto Campo , Baker Sarah , Burton Nicola W , Eghbali Mohammad , Fernandez Natalia , Ferreira Ricardo , Gäbler Gabriele , Makri Souzi , Mintz Sandra , Moe Rikke , Morasso Elizabeth , Murphy Susan L , Ntuli Simiso , Omara Maisa , Simancas Pallares Miguel Angel , Horonieff Jen , Gartlehner Gerald 
Published: June 2020

AbstractBackgroundThe number of published clinical practice guidelines and recommendations related to SARS-CoV-2 infections causing COVID-19 has rapidly increased. However, insufficient consideration of appropriate methodologies in the guideline development could lead to misleading information, uncertainty among professionals, and potentially harmful actions for patients.PurposeRapid systematic review of clinical practice guidelines and recommendations in the context of COVID-19 to explore if basic methodological standards of guideline development have been met.Data sourcesMEDLINE [PubMed], CINAHL [Ebsco], Trip and manual search; from Feb 1st 2020 until April 27th 2020.Study selectionAll types of healthcare workers providing any kind of healthcare to any patient population in any setting.Data extractionAt least two reviewers independently extracted guideline characteristics, conducted critical appraisal according to The Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II) and classified the guidelines using the Association of the Scientific Medical Societies (AWMF) Guidance Manual and Rules for Guideline Development. We plan six-month updates (living review).Data synthesisThere were 1342 titles screened and 188 guidelines included. The highest average AGREE II domain score was 89% for scope and purpose, the lowest for rigor of development (25%). Only eight guidelines (4%) were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality, S3 according to AWMF). Patients were only included in the development of one guideline. A process for regular updates was described in 27 guidelines (14%).LimitationsMethodological focus only.ConclusionsDespite clear scope, most publications fell short of basic methodological standards of guideline development. Future research should monitor the evolving methodological quality of the guidelines and their updates over time.Registration/PublicationThe protocol was published at www.researchgate.net, DOI: 10.13140/RG.2.2.21293.51689. Preliminary results are publicly available on medRxiv.
Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19
Authors: Bramante Carolyn T. , Ingraham Nicholas E. , Murray Thomas A. , Marmor Schelomo , Hovertsen Shane , Gronski Jessica , McNeil Chace , Feng Ruoying , Guzman Gabriel , Abdelwahab Nermine , King Samantha , Meehan Thomas , Pendleton Kathryn M. , Benson Bradley , Vojta Deneen , Tignanelli Christopher J. 
Published: June 2020

AbstractImportanceType 2 diabetes (T2DM) and obesity are significant risk factors for mortality in Covid19. Metformin has sex specific immunomodulatory effects which may elucidate treatment mechanisms in COVID-19.Objective:We sought to identify whether metformin reduced mortality from Covid19 and if sex specific interactions exist.DesignRetrospective review of de-identified claims from UnitedHealth Group’s Clinical Discovery Database. Unadjusted and multivariate models were conducted to assess risk of mortality based on metformin and tumor necrosis factor alpha (TNFα) inhibitors as home medications in individuals with T2DM and obesity, controlling for comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex.SettingThe database includes all 50 states in the United States.Participants:Persons with at least 6 months of continuous coverage from UnitedHealth Group in 2019 who were hospitalized with Covid-19. Persons in the metformin group had > 90 days of metformin claims in the 12 months before hospitalization.Results6,256 persons were included; 52.8% female; mean age 75 years. Metformin was associated with decreased mortality in women by logistic regression, OR 0.792 (0.640, 0.979); mixed effects OR 0.780 (0.631, 0.965); Cox proportional-hazards: HR 0.785 (0.650, 0.951); and propensity matching, OR of 0.759 (0.601, 0.960). There was no significant reduction in mortality among men. TNFα inhibitors were associated with decreased mortality, by propensity matching in a limited model, OR 0.19 (0.0378, 0.983).ConclusionsMetformin was significantly associated with reduced mortality in women with obesity or T2DM in observational analyses of claims data from individuals hospitalized with Covid-19. This sex-specific finding is consistent with metformin’s reduction of TNFα in females over males, and suggests that metformin conveys protection in Covid-19 through TNFα effects. Prospective studies are needed to understand mechanism and causality.Key PointsQuestionMetformin has many anti-inflammatory effects, including sex-specific effects on TNFα. Is metformin protective from the Sars-CoV-2 virus, and does the effect differ by sex?FindingsMetformin was associated with reduced mortality in women who were hospitalized with Covid-19, but not in men who were hospitalized with Covid-19.MeaningThe sex-dependent survival by metformin use points towards TNFα reduction as a key mechanism for protection from Covid-19.
Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis
Authors:   The OpenSAFELY Collaborative, Schultze Anna , Walker Alex J , MacKenna Brian , Morton Caroline E , Bhaskaran Krishnan , Brown Jeremy P , Rentsch Christopher T , Williamson Elizabeth , Drysdale Henry , Croker Richard , Bacon Seb , Hulme William , Bates Chris , Curtis Helen J , Mehrkar Amir , Evans David , Inglesby Peter , Cockburn Jonathan , McDonald Helen I , Tomlinson Laurie , Mathur Rohini , Wing Kevin , Wong Angel YS , Forbes Harriet , Parry John , Hester Frank , Harper Sam , Evans Stephen JW , Quint Jennifer , Smeeth Liam , Douglas Ian J , Goldacre Ben 
Published: June 2020

AbstractBackgroundEarly descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK.MethodsWe conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death.FindingsWe identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 – 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 – 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 – 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations.InterpretationThese results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity.FundingThis work was supported by the Medical Research Council MR/V015737/1.