Showing papers by "Columbia University published in 2021"
TL;DR: A comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae is provided in this paper, where the authors discuss relevant considerations for the multidisciplinary care of COPD survivors and propose a framework for the identification of those at high risk for COPD and their coordinated management through dedicated COPD clinics.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
2,307 citations
TL;DR: In this paper, the authors show that B.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclanal antibody against the receptor-binding domain.
Abstract: The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1-3, and more treatments are under development4-7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.
1,641 citations
TL;DR: In this paper, the authors provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of the potential therapeutic roles, and its pathological roles, together with a potential for therapeutic targeting.
Abstract: The research field of ferroptosis has seen exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity and metabolism of amino acids, lipids and sugars, in addition to various signalling pathways relevant to disease. Numerous organ injuries and degenerative pathologies are driven by ferroptosis. Intriguingly, therapy-resistant cancer cells, particularly those in the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. As such, pharmacological modulation of ferroptosis, via both its induction and its inhibition, holds great potential for the treatment of drug-resistant cancers, ischaemic organ injuries and other degenerative diseases linked to extensive lipid peroxidation. In this Review, we provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of ferroptosis in tumour suppression and immune surveillance, and its pathological roles, together with a potential for therapeutic targeting. Importantly, as in all rapidly evolving research areas, challenges exist due to misconceptions and inappropriate experimental methods. This Review also aims to address these issues and to provide practical guidelines for enhancing reproducibility and reliability in studies of ferroptosis. Finally, we discuss important concepts and pressing questions that should be the focus of future ferroptosis research.
1,243 citations
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
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
University College London1, International Institute for Applied Systems Analysis2, University of Reading3, United Nations University4, University of London5, University of Colorado Boulder6, Umeå University7, Tsinghua University8, World Health Organization9, Cardiff University10, University of Geneva11, University of New England (United States)12, University of Birmingham13, Yale University14, University of Washington15, Northeastern University16, Virginia Tech17, University of Oxford18, University of York19, International Livestock Research Institute20, Cayetano Heredia University21, Harvard University22, Boston University23, University of Sussex24, Nelson Marlborough Institute of Technology25, Emory University26, Columbia University27, Autonomous University of Barcelona28, Technische Universität München29, University of Melbourne30, Iran University of Medical Sciences31, University of Exeter32, Imperial College London33, University of Sheffield34, European Centre for Disease Prevention and Control35, Universiti Malaysia Terengganu36, University of Santiago de Compostela37
TL;DR: TRANSLATIONS For the Chinese, French, German, and Spanish translations of the abstract see Supplementary Materials section.
886 citations
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, National Research Council9, University of Padua10, 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
TL;DR: In this paper, the authors report that B.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mabs to the receptor-binding domain (RBD).
Abstract: The Covid-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Two monoclonal antibody (mAb) therapeutics have received emergency use authorization, and more are in the pipeline. Furthermore, multiple vaccine constructs have shown promise, including two with ~95% protective efficacy against Covid-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. Considerable viral evolution has occurred since, including variants with a D614G mutation that have become dominant. Viruses with this mutation alone do not appear to be antigenically distinct, however. Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD). It is modestly more resistant to convalescent plasma (~3 fold) and vaccinee sera (~2 fold). Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple potent mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccinee sera (~6.5-8.6 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.
677 citations
TL;DR: In this paper, the authors report that B.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mabs to the receptor-binding domain (RBD).
Abstract: The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1-3, with more in the pipeline4-7. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-199,10. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.
551 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, Columbia University3, National Research University – Higher School of Economics4, Yale University5, University of Lagos6, Institute for Fiscal Studies7, Universidade Nova de Lisboa8, Lahore University of Management Sciences9, University of St Andrews10, Stockholm School of Economics11, Ghent University12, Alternatives13, Trinity College, Dublin14, University of Sierra Leone15, Kathmandu16, Cornell University17, University of Illinois at Chicago18, New York University Abu Dhabi19, Princeton University20, Stockholm University21, Tufts University22, University of Michigan23, Northwestern University24, London School of Economics and Political Science25
TL;DR: In this article, the authors analyzed COVID-19 vaccine acceptance across 15 survey samples covering 10 low and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals.
Abstract: Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
536 citations
University College London1, University of Reading2, University of York3, United Nations University4, University of London5, Tsinghua University6, World Health Organization7, Cardiff University8, Yale University9, University of Birmingham10, University of Greenwich11, University of Washington12, Northeastern University13, Virginia Tech14, International Livestock Research Institute15, National University of Singapore16, Cayetano Heredia University17, Harvard University18, International Institute for Applied Systems Analysis19, Boston University20, University of Sussex21, Nelson Marlborough Institute of Technology22, Emory University23, Columbia University24, Autonomous University of Barcelona25, Technische Universität München26, University of Melbourne27, University of Copenhagen28, Iran University of Medical Sciences29, Technical University of Denmark30, Umeå University31, Max Planck Society32, University of Colorado Boulder33, University of Exeter34, University of Oxford35, Universiti Malaysia Terengganu36, University of Santiago de Compostela37, University of Hong Kong38
TL;DR: The 2021 report of the Lancet Countdown on health and climate change : code red for a healthy future as mentioned in this paper, is the most recent publication of the Countdown on Health and Climate Change, 2019.
491 citations
TL;DR: In this article, the population of 47 compact binary mergers detected with a false-alarm rate of 0.614 were dynamically assembled, and the authors found that the BBH rate likely increases with redshift, but not faster than the star formation rate.
Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.
TL;DR: The P.1 trimer adopts exclusively a conformation in which one of the receptor-binding domains is in the "up" position, which is known to facilitate binding to the entry receptor ACE2.
TL;DR: The literature review focuses primarily on U.S.-based studies of adults with diabetes and on key definitions and SDOH frameworks, and concludes with recommendations for linkages across health care and community sectors from national advisory committees, recommendations for diabetes research, and recommendations for research to inform practice.
Abstract: Decades of research have demonstrated that diabetes affects racial and ethnic minority and low-income adult populations in the U.S. disproportionately, with relatively intractable patterns seen in these populations’ higher risk of diabetes and rates of diabetes complications and mortality (1). With a health care shift toward greater emphasis on population health outcomes and value-based care, social determinants of health (SDOH) have risen to the forefront as essential intervention targets to achieve health equity (2–4). Most recently, the COVID-19 pandemic has highlighted unequal vulnerabilities borne by racial and ethnic minority groups and by disadvantaged communities. In the wake of concurrent pandemic and racial injustice events in the U.S., the American College of Physicians, American Academy of Pediatrics, Society of General Internal Medicine, National Academy of Medicine, and other professional organizations have published statements on SDOH (5–8), and calls to action focus on amelioration of these determinants at individual, organizational, and policy levels (9–11).
In diabetes, understanding and mitigating the impact of SDOH are priorities due to disease prevalence, economic costs, and disproportionate population burden (12–14). In 2013, the American Diabetes Association (ADA) published a scientific statement on socioecological determinants of prediabetes and type 2 diabetes (15). Toward the goal ofunderstanding and advancing opportunities for health improvement among the population with diabetes through addressing SDOH, ADA convened the current SDOH and diabetes writing committee, prepandemic, to review the literature on 1 ) associations of SDOH with diabetes risk and outcomes and 2 ) impact of interventions targeting amelioration of SDOH on diabetes outcomes. This article begins with an overview of key definitions and SDOH frameworks. The literature review focuses primarily on U.S.-based studies of adults with diabetes and on five SDOH: socioeconomic status (education, income, occupation); neighborhood and physical environment (housing, built environment, toxic environmental …
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30 Nov 2021TL;DR: The Sustainable Development Report 2021 as mentioned in this paper presents the SDG Index and Dashboards, the first and widely used tool to assess country performance on the UN Agenda 2030 and the sustainable development goals.
Abstract: The Sustainable Development Report 2021 features the SDG Index and Dashboards, the first and widely used tool to assess country performance on the UN Agenda 2030 and the Sustainable Development Goals. The report analyses and outlines what needs to happen for the Decade of Action and Delivery of the SDGs. In order to build back better following the Covid-19 pandemic, especially low-income countries will need increased fiscal space. The report frames the implementation of the SDGs in terms of six broad transformations. The authors examine country performance on the SDGs for 193 countries using a wide array of indicators, and calculate future trajectories, presenting a number of best practices to achieve the historic Agenda 2030. The views expressed in this report do not reflect the views of any organizations, agency or programme of the United Nations. This title is available as Open Access on Cambridge Core.
TL;DR: Overall, this work provides a genome-scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection.
Centre for Mental Health1, Swansea University2, University of Sydney3, University of Manchester4, Griffith University5, University College Cork6, Stellenbosch University7, Sao Paulo State University8, University of Zagreb9, University of Rochester Medical Center10, University of Udine11, National Taiwan University12, Innsbruck Medical University13, Yale University14, Johns Hopkins University15, Australian National University16, Brigham and Women's Hospital17, University of Auckland18, Hobart Corporation19, Columbia University Medical Center20, University of Oxford21, National Institute for Health Research22, Aga Khan University23, Katholieke Universiteit Leuven24, University of Peradeniya25, University of Bristol26, World Health Organization27, Karolinska Institutet28, First Pavlov State Medical University of St. Peterburg29, Medical University of Vienna30, University of Nottingham31, University of Glasgow32, University of Edinburgh33, Columbia University34, Shanghai Jiao Tong University35, University of Ulm36, University of Oslo37, Goethe University Frankfurt38, Saint Petersburg State University39, University of Toronto40, Sunnybrook Health Sciences Centre41, Waseda University42, Rajarata University of Sri Lanka43, Tel Aviv University44, University Hospitals Bristol NHS Foundation Trust45
TL;DR: In this article, the early effect of the COVID-19 pandemic on suicide rates around the world was assessed using real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature.
TL;DR: In this paper, the recently licensed vaccines for COVID-19 activate innate immune mechanisms to promote immune memory to SARS-CoV-2 and consider the future implications of protecting populations with these vaccines.
Abstract: The new vaccines against SARS-CoV-2 are novel in terms of specificity, their wide dissemination across the global population and the inclusion of newly licensed mRNA platforms. We discuss here how the approved vaccines trigger innate immunity to promote durable immunological memory and consider the future implications of protecting populations with these vaccines. This Comment outlines how the recently licensed vaccines for COVID-19 activate innate immune mechanisms to promote immune memory to SARS-CoV-2. The authors also consider future challenges that could limit vaccine efficacy.
TL;DR: In this paper, the authors show distinct antibody responses in children and adults after SARS-CoV-2 infection, indicating a distinct infection course and immune response in children independent of whether they develop multisystem inflammatory syndrome (MIS-C).
Abstract: Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.
Broad Institute1, Harvard University2, Columbia University3, University of Helsinki4, Beth Israel Deaconess Medical Center5, Brigham and Women's Hospital6, NanoString Technologies7, Stanford University8, University of Southern California9, Massachusetts Institute of Technology10, Duke University11, Wyss Institute for Biologically Inspired Engineering12, Boston Children's Hospital13, Genentech14
TL;DR: In this article, single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe SARS-CoV-2 infection.
Abstract: COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1–4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments. Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.
TL;DR: In this article, the authors reported the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries.
Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.
University of Maryland, College Park1, University of Illinois at Urbana–Champaign2, Columbia University3, Goddard Space Flight Center4, Hoffmann-La Roche5, University of Toulouse6, Haverford College7, Stony Brook University8, University of Alberta9, United States Naval Research Laboratory10, Centre national de la recherche scientifique11, University of Orléans12, Cornell University13, Max Planck Society14, Eötvös Loránd University15, National Radio Astronomy Observatory16, University of British Columbia17
TL;DR: In this article, the authors reported a radius measurement based on fits of rotating hot spot patterns to Neutron Star Interior Composition Explorer (NICER) and X-ray Multi-Mirror (XMM-Newton) observations.
Abstract: PSR J0740$+$6620 has a gravitational mass of $2.08\pm 0.07~M_\odot$, which is the highest reliably determined mass of any neutron star. As a result, a measurement of its radius will provide unique insight into the properties of neutron star core matter at high densities. Here we report a radius measurement based on fits of rotating hot spot patterns to Neutron Star Interior Composition Explorer (NICER) and X-ray Multi-Mirror (XMM-Newton) X-ray observations. We find that the equatorial circumferential radius of PSR J0740$+$6620 is $13.7^{+2.6}_{-1.5}$ km (68%). We apply our measurement, combined with the previous NICER mass and radius measurement of PSR J0030$+$0451, the masses of two other $\sim 2~M_\odot$ pulsars, and the tidal deformability constraints from two gravitational wave events, to three different frameworks for equation of state modeling, and find consistent results at $\sim 1.5-3$ times nuclear saturation density. For a given framework, when all measurements are included the radius of a $1.4~M_\odot$ neutron star is known to $\pm 4$% (68% credibility) and the radius of a $2.08~M_\odot$ neutron star is known to $\pm 5$%. The full radius range that spans the $\pm 1\sigma$ credible intervals of all the radius estimates in the three frameworks is $12.45\pm 0.65$ km for a $1.4~M_\odot$ neutron star and $12.35\pm 0.75$ km for a $2.08~M_\odot$ neutron star.
University of Colorado Boulder1, University of North Carolina at Chapel Hill2, University of Notre Dame3, University of South Florida4, Columbia University5, University of California, Irvine6, Rutgers University7, Stony Brook University8, University of Pittsburgh9, Yale University10, University of Oregon11, University of California, Berkeley12, Boston University13, Vanderbilt University14, University of Miami15, University of Minnesota16, Fordham University17, Harvard University18, Cornell University19, University of Michigan20, University of Central Florida21, University of California, Los Angeles22, University of Virginia23, Brown University24
TL;DR: COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training.
Abstract: COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this article, COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
University of Amsterdam1, United States Naval Research Laboratory2, Columbia University3, University of Toulouse4, Hoffmann-La Roche5, University of Alberta6, ASTRON7, Goddard Space Flight Center8, Los Alamos National Laboratory9, Haverford College10, Stony Brook University11, University of Maryland, College Park12, California Institute of Technology13, University of New Hampshire14, Vassar College15, Cornell University16, Eötvös Loránd University17, National Radio Astronomy Observatory18, Max Planck Society19, University of British Columbia20, Centre national de la recherche scientifique21, University of Orléans22
TL;DR: In this article, the authors estimate the radius, mass, and hot surface regions of the massive millisecond pulsar PSR J0740$+$6620, conditional on pulse profile modeling of Neutron Star Interior Composition Explorer X-ray Timing Instrument (NICER XTI) event data.
Abstract: We report on Bayesian estimation of the radius, mass, and hot surface regions of the massive millisecond pulsar PSR J0740$+$6620, conditional on pulse-profile modeling of Neutron Star Interior Composition Explorer X-ray Timing Instrument (NICER XTI) event data. We condition on informative pulsar mass, distance, and orbital inclination priors derived from the joint NANOGrav and CHIME/Pulsar wideband radio timing measurements of arXiv:2104.00880. We use XMM European Photon Imaging Camera spectroscopic event data to inform our X-ray likelihood function. The prior support of the pulsar radius is truncated at 16 km to ensure coverage of current dense matter models. We assume conservative priors on instrument calibration uncertainty. We constrain the equatorial radius and mass of PSR J0740$+$6620 to be $12.39_{-0.98}^{+1.30}$ km and $2.072_{-0.066}^{+0.067}$ M$_{\odot}$ respectively, each reported as the posterior credible interval bounded by the 16% and 84% quantiles, conditional on surface hot regions that are non-overlapping spherical caps of fully-ionized hydrogen atmosphere with uniform effective temperature; a posteriori, the temperature is $\log_{10}(T$ [K]$)=5.99_{-0.06}^{+0.05}$ for each hot region. All software for the X-ray modeling framework is open-source and all data, model, and sample information is publicly available, including analysis notebooks and model modules in the Python language. Our marginal likelihood function of mass and equatorial radius is proportional to the marginal joint posterior density of those parameters (within the prior support) and can thus be computed from the posterior samples.
TL;DR: In this article, the NTD-directed neutralizing antibody targets a single supersite, formed primarily by a mobile β-hairpin and several flexible loops, and the largest glycan-free surface of NTD facing away from the viral membrane.
14 Jan 2021
TL;DR: This Primer on Bayesian statistics summarizes the most important aspects of determining prior distributions, likelihood functions and posterior distributions, in addition to discussing different applications of the method across disciplines.
Abstract: Bayesian statistics is an approach to data analysis based on Bayes’ theorem, where available knowledge about parameters in a statistical model is updated with the information in observed data. The background knowledge is expressed as a prior distribution and combined with observational data in the form of a likelihood function to determine the posterior distribution. The posterior can also be used for making predictions about future events. This Primer describes the stages involved in Bayesian analysis, from specifying the prior and data models to deriving inference, model checking and refinement. We discuss the importance of prior and posterior predictive checking, selecting a proper technique for sampling from a posterior distribution, variational inference and variable selection. Examples of successful applications of Bayesian analysis across various research fields are provided, including in social sciences, ecology, genetics, medicine and more. We propose strategies for reproducibility and reporting standards, outlining an updated WAMBS (when to Worry and how to Avoid the Misuse of Bayesian Statistics) checklist. Finally, we outline the impact of Bayesian analysis on artificial intelligence, a major goal in the next decade. This Primer on Bayesian statistics summarizes the most important aspects of determining prior distributions, likelihood functions and posterior distributions, in addition to discussing different applications of the method across disciplines.
TL;DR: In this paper, the OPLS4 force field was developed and validated on a drug-like chemical space that includes molecular ions and sulfur-containing moieties, and a novel parametrization strategy for charged species, which can be extended to other systems.
Abstract: We report on the development and validation of the OPLS4 force field. OPLS4 builds upon our previous work with OPLS3e to improve model accuracy on challenging regimes of drug-like chemical space that includes molecular ions and sulfur-containing moieties. A novel parametrization strategy for charged species, which can be extended to other systems, is introduced. OPLS4 leads to improved accuracy on benchmarks that assess small-molecule solvation and protein-ligand binding.
Georgetown University1, Tufts Medical Center2, Anschutz Medical Campus3, Indiana University4, Columbia University5, Emory University6, West Virginia University7, Society of Thoracic Surgeons8, University of Florida9, University of Alabama at Birmingham10, University of Michigan11, Henry Ford Hospital12
TL;DR: The Society of Thoracic Surgeons (STS)-Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 2020 Annual Report reviews outcomes on 25,551 patients undergoing primary isolated continuous-flow left ventricular assist device (LVAD) implantation between 2010 and 2019 as discussed by the authors.
TL;DR: The data recorded by these instruments during their first and second observing runs are described, including the gravitational-wave strain arrays, released as time series sampled at 16384 Hz.
01 Jun 2021
TL;DR: Analysis reveals that PLBART learns program syntax, style, logical flow, and style that are crucial to program semantics and thus excels even with limited annotations, and outperforms or rivals state-of-the-art models.
Abstract: Code summarization and generation empower conversion between programming language (PL) and natural language (NL), while code translation avails the migration of legacy code from one PL to another. This paper introduces PLBART, a sequence-to-sequence model capable of performing a broad spectrum of program and language understanding and generation tasks. PLBART is pre-trained on an extensive collection of Java and Python functions and associated NL text via denoising autoencoding. Experiments on code summarization in the English language, code generation, and code translation in seven programming languages show that PLBART outperforms or rivals state-of-the-art models. Moreover, experiments on discriminative tasks, e.g., program repair, clone detection, and vulnerable code detection, demonstrate PLBART’s effectiveness in program understanding. Furthermore, analysis reveals that PLBART learns program syntax, style (e.g., identifier naming convention), logical flow (e.g., “if“ block inside an “else“ block is equivalent to “else if“ block) that are crucial to program semantics and thus excels even with limited annotations.
Boston Children's Hospital1, University of North Carolina at Chapel Hill2, Columbia University3, Northwestern University4, Ohio State University5, Stanford University6, University of Washington7, University of Toronto8, Broad Institute9, University of Arkansas for Medical Sciences10, Oregon Health & Science University11
TL;DR: Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this statement, and to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.