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Showing papers by "Oregon Health & Science University published in 2021"


Journal ArticleDOI
29 Mar 2021-BMJ
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

16,613 citations


Journal ArticleDOI
29 Mar 2021-BMJ
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) as mentioned in this paper was developed to facilitate transparent and complete reporting of systematic reviews, and has been updated to reflect recent advances in systematic review methodology and terminology.
Abstract: The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.

2,217 citations


Journal ArticleDOI
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

2,192 citations



Journal ArticleDOI
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

1,129 citations


Journal ArticleDOI
TL;DR: In this paper, the authors conducted an online survey of people with confirmed and confirmed COVID-19, distributed via COVID19 support groups and social media (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters).

996 citations


Journal ArticleDOI
TL;DR: In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo.
Abstract: Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failu...

913 citations


Journal ArticleDOI
TL;DR: The PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses, was proposed by Page and colleagues as discussed by the authors, who describe the guidelines as "an updated reporting guidelines for systematic review and meta analysis".
Abstract: Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

824 citations


Journal ArticleDOI
Carole Escartin1, Elena Galea2, Andras Lakatos3, James P. O'Callaghan4, Gabor C. Petzold5, Gabor C. Petzold6, Alberto Serrano-Pozo7, Christian Steinhäuser6, Andrea Volterra8, Giorgio Carmignoto9, Giorgio Carmignoto10, Amit Agarwal11, Nicola J. Allen12, Alfonso Araque13, Luis Barbeito14, Ari Barzilai15, Dwight E. Bergles16, Gilles Bonvento1, Arthur M. Butt17, Wei Ting Chen18, Martine Cohen-Salmon19, Colm Cunningham20, Benjamin Deneen21, Bart De Strooper18, Bart De Strooper22, Blanca Diaz-Castro23, Cinthia Farina, Marc R. Freeman24, Vittorio Gallo25, James E. Goldman26, Steven A. Goldman27, Steven A. Goldman28, Magdalena Götz29, Antonia Gutierrez30, Philip G. Haydon31, Dieter Henrik Heiland32, Elly M. Hol33, Matthew Holt18, Masamitsu Iino34, Ksenia V. Kastanenka7, Helmut Kettenmann35, Baljit S. Khakh36, Schuichi Koizumi37, C. Justin Lee, Shane A. Liddelow38, Brian A. MacVicar39, Pierre J. Magistretti40, Pierre J. Magistretti8, Albee Messing41, Anusha Mishra24, Anna V. Molofsky42, Keith K. Murai43, Christopher M. Norris44, Seiji Okada45, Stéphane H. R. Oliet46, João Filipe Oliveira47, João Filipe Oliveira48, Aude Panatier46, Vladimir Parpura49, Marcela Pekna50, Milos Pekny50, Luc Pellerin51, Gertrudis Perea52, Beatriz G. Pérez-Nievas53, Frank W. Pfrieger54, Kira E. Poskanzer42, Francisco J. Quintana7, Richard M. Ransohoff, Miriam Riquelme-Perez1, Stefanie Robel55, Christine R. Rose56, Jeffrey D. Rothstein16, Nathalie Rouach19, David H. Rowitch3, Alexey Semyanov57, Alexey Semyanov58, Swetlana Sirko29, Harald Sontheimer55, Raymond A. Swanson42, Javier Vitorica59, Ina B. Wanner36, Levi B. Wood60, Jia Qian Wu61, Binhai Zheng62, Eduardo R. Zimmer63, Robert Zorec64, Michael V. Sofroniew36, Alexei Verkhratsky65, Alexei Verkhratsky66 
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, German Center for Neurodegenerative Diseases5, University of Bonn6, Harvard University7, University of Lausanne8, University of Padua9, National Research Council10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Copenhagen27, University of Rochester28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, University of Minho47, Polytechnic Institute of Cávado and Ave48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, I.M. Sechenov First Moscow State Medical University57, Russian Academy of Sciences58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, Ikerbasque65, University of Manchester66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

797 citations


Journal ArticleDOI
TL;DR: In this paper, Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer and remains fatal despite recent advances in medical technology.
Abstract: Background Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-res...

696 citations


Journal ArticleDOI
Arang Rhie1, Shane A. McCarthy2, Shane A. McCarthy3, Olivier Fedrigo4, Joana Damas5, Giulio Formenti4, Sergey Koren1, Marcela Uliano-Silva6, William Chow2, Arkarachai Fungtammasan, J. H. Kim7, Chul Hee Lee7, Byung June Ko7, Mark Chaisson8, Gregory Gedman4, Lindsey J. Cantin4, Françoise Thibaud-Nissen1, Leanne Haggerty9, Iliana Bista3, Iliana Bista2, Michelle Smith2, Bettina Haase4, Jacquelyn Mountcastle4, Sylke Winkler10, Sylke Winkler11, Sadye Paez4, Jason T. Howard, Sonja C. Vernes10, Sonja C. Vernes12, Sonja C. Vernes13, Tanya M. Lama14, Frank Grützner15, Wesley C. Warren16, Christopher N. Balakrishnan17, Dave W Burt18, Jimin George19, Matthew T. Biegler4, David Iorns, Andrew Digby, Daryl Eason, Bruce C. Robertson20, Taylor Edwards21, Mark Wilkinson22, George F. Turner23, Axel Meyer24, Andreas F. Kautt25, Andreas F. Kautt24, Paolo Franchini24, H. William Detrich26, Hannes Svardal27, Hannes Svardal28, Maximilian Wagner29, Gavin J. P. Naylor30, Martin Pippel10, Milan Malinsky2, Milan Malinsky31, Mark Mooney, Maria Simbirsky, Brett T. Hannigan, Trevor Pesout32, Marlys L. Houck33, Ann C Misuraca33, Sarah B. Kingan34, Richard Hall34, Zev N. Kronenberg34, Ivan Sović34, Christopher Dunn34, Zemin Ning2, Alex Hastie, Joyce V. Lee, Siddarth Selvaraj, Richard E. Green32, Nicholas H. Putnam, Ivo Gut35, Jay Ghurye36, Erik Garrison32, Ying Sims2, Joanna Collins2, Sarah Pelan2, James Torrance2, Alan Tracey2, Jonathan Wood2, Robel E. Dagnew8, Dengfeng Guan3, Dengfeng Guan37, Sarah E. London38, David F. Clayton19, Claudio V. Mello39, Samantha R. Friedrich39, Peter V. Lovell39, Ekaterina Osipova10, Farooq O. Al-Ajli40, Farooq O. Al-Ajli41, Simona Secomandi42, Heebal Kim7, Constantina Theofanopoulou4, Michael Hiller43, Yang Zhou, Robert S. Harris44, Kateryna D. Makova44, Paul Medvedev44, Jinna Hoffman1, Patrick Masterson1, Karen Clark1, Fergal J. Martin9, Kevin L. Howe9, Paul Flicek9, Brian P. Walenz1, Woori Kwak, Hiram Clawson32, Mark Diekhans32, Luis R Nassar32, Benedict Paten32, Robert H. S. Kraus24, Robert H. S. Kraus10, Andrew J. Crawford45, M. Thomas P. Gilbert46, M. Thomas P. Gilbert47, Guojie Zhang, Byrappa Venkatesh48, Robert W. Murphy49, Klaus-Peter Koepfli50, Beth Shapiro51, Beth Shapiro32, Warren E. Johnson52, Warren E. Johnson50, Federica Di Palma53, Tomas Marques-Bonet, Emma C. Teeling54, Tandy Warnow55, Jennifer A. Marshall Graves56, Oliver A. Ryder33, Oliver A. Ryder57, David Haussler32, Stephen J. O'Brien58, Jonas Korlach34, Harris A. Lewin5, Kerstin Howe2, Eugene W. Myers10, Eugene W. Myers11, Richard Durbin2, Richard Durbin3, Adam M. Phillippy1, Erich D. Jarvis4, Erich D. Jarvis51 
National Institutes of Health1, Wellcome Trust Sanger Institute2, University of Cambridge3, Rockefeller University4, University of California, Davis5, Leibniz Association6, Seoul National University7, University of Southern California8, European Bioinformatics Institute9, Max Planck Society10, Dresden University of Technology11, University of St Andrews12, Radboud University Nijmegen13, University of Massachusetts Amherst14, University of Adelaide15, University of Missouri16, East Carolina University17, University of Queensland18, Clemson University19, University of Otago20, University of Arizona21, Natural History Museum22, Bangor University23, University of Konstanz24, Harvard University25, Northeastern University26, University of Antwerp27, National Museum of Natural History28, University of Graz29, University of Florida30, University of Basel31, University of California, Santa Cruz32, Zoological Society of San Diego33, Pacific Biosciences34, Pompeu Fabra University35, University of Maryland, College Park36, Harbin Institute of Technology37, University of Chicago38, Oregon Health & Science University39, Monash University Malaysia Campus40, Qatar Airways41, University of Milan42, Goethe University Frankfurt43, Pennsylvania State University44, University of Los Andes45, Norwegian University of Science and Technology46, University of Copenhagen47, Agency for Science, Technology and Research48, Royal Ontario Museum49, Smithsonian Institution50, Howard Hughes Medical Institute51, Walter Reed Army Institute of Research52, University of East Anglia53, University College Dublin54, University of Illinois at Urbana–Champaign55, La Trobe University56, University of California, San Diego57, Nova Southeastern University58
28 Apr 2021-Nature
TL;DR: The Vertebrate Genomes Project (VGP) as mentioned in this paper is an international effort to generate high quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
Abstract: High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.


Journal ArticleDOI
TL;DR: A systematic review evaluating racial/ethnic disparities in SARS-CoV-2 infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them suggests that impacts of CO VID-19 differ among U.S. racial/ ethnic groups.
Abstract: BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. (PROSPERO: CRD42020187078). DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development.

Journal ArticleDOI
09 Mar 2021-JAMA
TL;DR: The US Preventive Services Task Force (USPSTF) concluded with moderate certainty that annual screening for lung cancer with LDCT has a moderate net benefit in persons at high risk of lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking as mentioned in this paper.
Abstract: Importance Lung cancer is the second most common cancer and the leading cause of cancer death in the US. In 2020, an estimated 228 820 persons were diagnosed with lung cancer, and 135 720 persons died of the disease. The most important risk factor for lung cancer is smoking. Increasing age is also a risk factor for lung cancer. Lung cancer has a generally poor prognosis, with an overall 5-year survival rate of 20.5%. However, early-stage lung cancer has a better prognosis and is more amenable to treatment. Objective To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the accuracy of screening for lung cancer with low-dose computed tomography (LDCT) and on the benefits and harms of screening for lung cancer and commissioned a collaborative modeling study to provide information about the optimum age at which to begin and end screening, the optimal screening interval, and the relative benefits and harms of different screening strategies compared with modified versions of multivariate risk prediction models. Population This recommendation statement applies to adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Evidence Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT has a moderate net benefit in persons at high risk of lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. Recommendation The USPSTF recommends annual screening for lung cancer with LDCT in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) This recommendation replaces the 2013 USPSTF statement that recommended annual screening for lung cancer with LDCT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.

Journal ArticleDOI
TL;DR: In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart Failure than placebo but was associated with adverse events.
Abstract: Background The efficacy and safety of sodium–glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney dise...

Journal ArticleDOI
TL;DR: Recent major extensions of the Human Phenotype Ontology for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas are presented and new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease are presented.
Abstract: The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

Journal ArticleDOI
TL;DR: In this article, neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials.
Abstract: Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.

Journal ArticleDOI
07 Jan 2021-PLOS ONE
TL;DR: It was showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously.
Abstract: Background University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general population. Therefore, when the nature of their educational experience radically changes—such as sheltering in place during the COVID-19 pandemic—the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts. Methods Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students. Results Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously. Conclusion Inadequate efforts to recognize and address college students’ mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.

Journal ArticleDOI
TL;DR: The Reactome Knowledgebase as mentioned in this paper provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes, annotated as an ordered network of molecular transformations in a single consistent data model.
Abstract: The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways.


Journal ArticleDOI
TL;DR: New, interim guidance to support the conduct of rapid reviews (RRs) produced within Cochrane and beyond is offered in response to requests for timely evidence syntheses for decision-making purposes including urgent health issues of high priority.

Journal ArticleDOI
23 Nov 2021-JAMA
TL;DR: In this article, the authors evaluated the association between vaccination with mRNA COVID-19 vaccines and hospitalization, and the association with progression to critical disease, using multivariable logistic regression.
Abstract: Importance A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. Objective To evaluate the association between vaccination with mRNA COVID-19 vaccines—mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)—and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. Design, Setting, and Participants A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. Exposures COVID-19 vaccination. Main Outcomes and Measures Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. Results Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P Conclusions and Relevance Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.

Journal ArticleDOI
TL;DR: In this article, the authors developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions to develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Abstract: Objective To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. Methods We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. Results The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). Conclusion This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

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TL;DR: In this article, the authors summarize the current understanding of the connection between copper and cancer and explore how challenges in the field could be addressed by using the framework of cuproplasia, which is defined as regulated copper-dependent cell proliferation and is a representative example of a broad range of metalloplasias.
Abstract: Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient. Indeed, the traditional view of copper as solely an active site metabolic cofactor has been challenged by emerging evidence that copper is also a dynamic signalling metal and metalloallosteric regulator, such as for copper-dependent phosphodiesterase 3B (PDE3B) in lipolysis, mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 in cell growth and proliferation and the kinases ULK1 and ULK2 in autophagy. In this Perspective, we summarize our current understanding of the connection between copper and cancer and explore how challenges in the field could be addressed by using the framework of cuproplasia, which is defined as regulated copper-dependent cell proliferation and is a representative example of a broad range of metalloplasias. Cuproplasia is linked to a diverse array of cellular processes, including mitochondrial respiration, antioxidant defence, redox signalling, kinase signalling, autophagy and protein quality control. Identifying and characterizing new modes of copper-dependent signalling offers translational opportunities that leverage disease vulnerabilities to this metal nutrient.


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TL;DR: In this paper, a case-control analysis was conducted among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021.
Abstract: Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.

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Richard R. Orlandi1, Todd T. Kingdom2, Timothy L. Smith3, Benjamin S. Bleier4, Adam S. DeConde5, Amber U Luong6, David M. Poetker7, Zachary M. Soler8, Kevin C. Welch9, Sarah K. Wise10, Nithin D. Adappa11, Jeremiah A. Alt1, Wilma Terezinha Anselmo-Lima12, Claus Bachert13, Claus Bachert14, Claus Bachert15, Fuad M. Baroody16, Pete S. Batra17, Manuel Bernal-Sprekelsen18, Daniel M. Beswick19, Neil Bhattacharyya4, Rakesh K. Chandra20, Eugene H. Chang21, Alexander G. Chiu22, Naweed I. Chowdhury20, Martin J. Citardi6, Noam A. Cohen11, David B. Conley9, John M. DelGaudio10, Martin Desrosiers23, Richard G. Douglas24, Jean Anderson Eloy25, Wytske Fokkens26, Stacey T. Gray4, David A. Gudis27, Daniel L. Hamilos4, Joseph K. Han28, Richard J. Harvey29, Peter Hellings30, Eric H. Holbrook4, Claire Hopkins31, Peter H. Hwang32, Amin R. Javer33, Rong San Jiang, David N. Kennedy11, Robert C. Kern9, Tanya M. Laidlaw4, Devyani Lal34, Andrew P. Lane35, Heung Man Lee36, Jivianne T. Lee19, Joshua M. Levy10, Sandra Y. Lin35, Valerie J. Lund, Kevin C. McMains37, Ralph Metson4, Joaquim Mullol18, Robert M. Naclerio35, Gretchen M. Oakley1, Nobuyoshi Otori38, James N. Palmer11, Sanjay R. Parikh39, Desiderio Passali40, Zara M. Patel32, Anju T. Peters9, Carl Philpott41, Alkis J. Psaltis42, Vijay R. Ramakrishnan2, Murugappan Ramanathan35, Hwan Jung Roh43, Luke Rudmik44, Raymond Sacks29, Rodney J. Schlosser8, Ahmad R. Sedaghat45, Brent A. Senior46, Raj Sindwani47, Kristine A. Smith48, Kornkiat Snidvongs49, Michael G. Stewart50, Jeffrey D. Suh19, Bruce K. Tan9, Justin H. Turner20, Cornelis M. van Drunen26, Richard Louis Voegels12, De Yun Wang51, Bradford A. Woodworth52, Peter-John Wormald42, Erin D. Wright53, Carol H. Yan5, Luo Zhang54, Bing Zhou54 
University of Utah1, University of Colorado Denver2, Oregon Health & Science University3, Harvard University4, University of California, San Diego5, University of Texas Health Science Center at Houston6, Medical College of Wisconsin7, Medical University of South Carolina8, Northwestern University9, Emory University10, University of Pennsylvania11, University of São Paulo12, Karolinska Institutet13, Ghent University14, Sun Yat-sen University15, University of Chicago16, Rush University Medical Center17, University of Barcelona18, University of California, Los Angeles19, Vanderbilt University20, University of Arizona21, University of Kansas22, Université de Montréal23, University of Auckland24, Rutgers University25, University of Amsterdam26, Columbia University27, Eastern Virginia Medical School28, University of New South Wales29, Katholieke Universiteit Leuven30, Guy's Hospital31, Stanford University32, University of British Columbia33, Mayo Clinic34, Johns Hopkins University35, Korea University36, Uniformed Services University of the Health Sciences37, Jikei University School of Medicine38, University of Washington39, University of Siena40, University of East Anglia41, University of Adelaide42, Pusan National University43, University of Calgary44, University of Cincinnati45, University of North Carolina at Chapel Hill46, Cleveland Clinic47, University of Winnipeg48, Chulalongkorn University49, Cornell University50, National University of Singapore51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in the understanding and treatment of rhinologic disease.
Abstract: I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

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TL;DR: The N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics.

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Stephen V. Faraone1, Tobias Banaschewski2, David Coghill3, Yi Zheng4, Joseph Biederman5, Mark A. Bellgrove6, Jeffrey H. Newcorn7, Martin Gignac8, Nouf M. Al Saud, Iris Manor, Luis Augusto Rohde9, Li Yang10, Samuele Cortese11, Doron Almagor12, Mark A. Stein13, Turki H. Albatti, Haya F. Aljoudi, Mohammed Alqahtani14, Philip Asherson15, Lukoye Atwoli16, Sven Bölte17, Jan K. Buitelaar18, Cleo L. Crunelle19, David Daley20, Søren Dalsgaard21, Manfred Döpfner22, Stacey Espinet, Michael Fitzgerald23, Barbara Franke18, Manfred Gerlach24, Jan Haavik25, Catharina A. Hartman26, Cynthia M. Hartung27, Stephen P. Hinshaw28, Stephen P. Hinshaw29, Pieter J. Hoekstra26, Chris Hollis30, Scott H. Kollins31, J. J. Sandra Kooij32, Jonna Kuntsi15, Henrik Larsson33, Henrik Larsson17, Tingyu Li34, Jing Liu10, Eugene Merzon35, Gregory Mattingly36, Paulo Mattos37, Suzanne McCarthy38, Amori Yee Mikami39, Brooke S. G. Molina40, Joel T. Nigg41, D. Purper-Ouakil42, Olayinka Omigbodun43, Guilherme V. Polanczyk44, Yehuda Pollak45, Alison Poulton46, Ravi Philip Rajkumar47, Andrew Reding, Andreas Reif, Katya Rubia15, Julia J. Rucklidge48, Marcel Romanos, J. Antoni Ramos-Quiroga49, Arnt F. A. Schellekens18, Anouk Scheres18, Renata Schoeman50, Julie B. Schweitzer51, Henal Shah52, Mary V. Solanto53, Edmund J.S. Sonuga-Barke15, Edmund J.S. Sonuga-Barke21, Cesar Soutullo54, Hans-Christoph Steinhausen55, James M. Swanson56, Anita Thapar57, Gail Tripp58, Geurt van de Glind59, Wim van den Brink32, Saskia Van der Oord60, André Venter61, Benedetto Vitiello62, Benedetto Vitiello63, Susanne Walitza64, Yufeng Wang10 
State University of New York Upstate Medical University1, Heidelberg University2, University of Melbourne3, Capital Medical University4, Harvard University5, Monash University, Clayton campus6, Icahn School of Medicine at Mount Sinai7, Montreal Children's Hospital8, Universidade Federal do Rio Grande do Sul9, Peking University10, University of Southampton11, University of Toronto12, University of Washington13, King Khalid University14, King's College London15, Aga Khan University16, Karolinska Institutet17, Radboud University Nijmegen18, Vrije Universiteit Brussel19, University of Nottingham20, Aarhus University21, University of Cologne22, Trinity College, Dublin23, University of Würzburg24, University of Bergen25, University Medical Center Groningen26, University of Wyoming27, University of California, San Francisco28, University of California, Berkeley29, Nottinghamshire Healthcare NHS Foundation Trust30, Duke University31, University of Amsterdam32, Örebro University33, Chongqing Medical University34, Tel Aviv University35, Washington University in St. Louis36, Federal University of Rio de Janeiro37, University College Cork38, University of British Columbia39, University of Pittsburgh40, Oregon Health & Science University41, University of Montpellier42, University of Ibadan43, University of São Paulo44, Hebrew University of Jerusalem45, University of Sydney46, Jawaharlal Institute of Postgraduate Medical Education and Research47, University of Canterbury48, Autonomous University of Barcelona49, Stellenbosch University50, University of California, Davis51, National Medical College52, Hofstra University53, University of Texas Health Science Center at Houston54, University of Southern Denmark55, University of California, Irvine56, Cardiff University57, Okinawa Institute of Science and Technology58, HU University of Applied Sciences Utrecht59, Katholieke Universiteit Leuven60, University of the Free State61, University of Turin62, Johns Hopkins University63, University of Zurich64
TL;DR: In this article, the authors presented 208 empirically supported statements about ADHD using meta-analysis, which allow for firm statements about the nature, course, outcome causes and treatments for disorders that are useful for reducing misconceptions and stigma.

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TL;DR: It is shown that intravenously injected radioiodinated S1 readily crossed the blood-brain barrier (BBB) in male mice, was taken up by brain regions and entered the parenchymal brain space, and I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation.
Abstract: It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood-brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration. APOE genotype and sex did not affect whole-brain I-S1 uptake but had variable effects on uptake by the olfactory bulb, liver, spleen and kidney. I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation. Mechanistic studies indicated that I-S1 crosses the blood-brain barrier by adsorptive transcytosis and that murine angiotensin-converting enzyme 2 is involved in brain and lung uptake, but not in kidney, liver or spleen uptake.