Showing papers by "Cornell University published in 2021"
University of Southern California1, French Institute for Research in Computer Science and Automation2, University of Oulu3, Princeton University4, University of Warwick5, Georgia Institute of Technology6, Rutgers University7, University of Virginia8, University of Washington9, Carnegie Mellon University10, École Polytechnique Fédérale de Lausanne11, University of Pittsburgh12, University of Wisconsin-Madison13, University of California, San Diego14, University of Illinois at Urbana–Champaign15, Nanyang Technological University16, Australian National University17, Stanford University18, IT University of Copenhagen19, Massachusetts Institute of Technology20, University of California, Berkeley21, Cornell University22, Emory University23, Hong Kong University of Science and Technology24
TL;DR: In this article, the authors describe the state-of-the-art in the field of federated learning from the perspective of distributed optimization, cryptography, security, differential privacy, fairness, compressed sensing, systems, information theory, and statistics.
Abstract: The term Federated Learning was coined as recently as 2016 to describe a machine learning setting where multiple entities collaborate in solving a machine learning problem, under the coordination of a central server or service provider. Each client’s raw data is stored locally and not exchanged or transferred; instead, focused updates intended for immediate aggregation are used to achieve the learning objective. Since then, the topic has gathered much interest across many different disciplines and the realization that solving many of these interdisciplinary problems likely requires not just machine learning but techniques from distributed optimization, cryptography, security, differential privacy, fairness, compressed sensing, systems, information theory, statistics, and more. This monograph has contributions from leading experts across the disciplines, who describe the latest state-of-the art from their perspective. These contributions have been carefully curated into a comprehensive treatment that enables the reader to understand the work that has been done and get pointers to where effort is required to solve many of the problems before Federated Learning can become a reality in practical systems. Researchers working in the area of distributed systems will find this monograph an enlightening read that may inspire them to work on the many challenging issues that are outlined. This monograph will get the reader up to speed quickly and easily on what is likely to become an increasingly important topic: Federated Learning.
2,144 citations
TL;DR: In this article, the authors report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
1,163 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
TL;DR: In this article, a systematic review and meta-analysis aimed to identify studies assessing the long-term effects of COVID-19, which can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery.
Abstract: COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17–87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.
969 citations
Memorial Sloan Kettering Cancer Center1, Cornell University2, University of Mainz3, Peking University4, Japanese Foundation for Cancer Research5, Medical University of Lublin6, Fudan University7, University of La Frontera8, Université de Montréal9, National and Kapodistrian University of Athens10, St John of God Murdoch Hospital11, Harvard University12, Bristol-Myers Squibb13, University of Texas MD Anderson Cancer Center14
TL;DR: The CheckMate 649 trial as discussed by the authors evaluated first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophage alogaryal adenocarcinoma.
858 citations
Ben-Gurion University of the Negev1, Population Health Research Institute2, McMaster University3, University of North Carolina at Chapel Hill4, Sanjay Gandhi Post Graduate Institute of Medical Sciences5, University of Gothenburg6, Katholieke Universiteit Leuven7, Iuliu Hațieganu University of Medicine and Pharmacy8, Peking Union Medical College Hospital9, Tohoku University10, University of Sydney11, University of Jos12, Cornell University13, National Autonomous University of Mexico14, University of Manchester15, University of Ghana16, Isfahan University of Medical Sciences17, University of Amsterdam18, Ege University19, Wonkwang University20, Universidade Federal do Rio Grande do Sul21, Pontifical Xavierian University22, Moscow State University of Medicine and Dentistry23, Universiti Sains Malaysia24, Wrocław Medical University25, Dhaka Medical College and Hospital26, Autonomous University of Barcelona27, University of Cape Town28, University of Indonesia29, Queen's University30, National University of Singapore31, Rabin Medical Center32, University of Alberta33, Mazandaran University of Medical Sciences34, Université de Montréal35
TL;DR: It is found that more than 40% of persons worldwide have FGIDs, which affect quality of life and healthcare use, and similar trends and relative distributions were found in people who completed internet vs personal interviews.
763 citations
TL;DR: Efficacy of the BNT162b2 mRNA Vaccine in Qatar As of March 31, 2021, more than 265,000 people in Qatar had received both doses of the vaccine as mentioned in this paper.
Abstract: Efficacy of the BNT162b2 mRNA Vaccine in Qatar As of March 31, 2021, more than 265,000 people in Qatar had received both doses of the BNT162b2 vaccine. Viral sequencing indicated that 50.0% of infe...
746 citations
Cornell University1, National University of Singapore2, University of New South Wales3, University of Lausanne4, University of Michigan5, Erasmus University Rotterdam6, Tel Aviv University7, University of Melbourne8, Singapore Management University9, University of Maryland, College Park10, University of Pennsylvania11, Eindhoven University of Technology12, Stanford University13, Concordia University14, London Business School15, Baylor University16, University College London17, California State University, Sacramento18, INSEAD19, Saint Louis University20, Nanyang Technological University21, University of Minnesota22, Harvard University23, University of Arkansas24, VU University Amsterdam25
TL;DR: A broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions.
Abstract: The impacts of COVID-19 on workers and workplaces across the globe have been dramatic. This broad review of prior research rooted in work and organizational psychology, and related fields, is intended to make sense of the implications for employees, teams, and work organizations. This review and preview of relevant literatures focuses on (a) emergent changes in work practices (e.g., working from home, virtual teamwork) and (b) emergent changes for workers (e.g., social distancing, stress, and unemployment). In addition, potential moderating factors (demographic characteristics, individual differences, and organizational norms) are examined given the likelihood that COVID-19 will generate disparate effects. This broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
654 citations
University of Texas MD Anderson Cancer Center1, Cornell University2, Roswell Park Cancer Institute3, University of Adelaide4, Sarah Cannon Research Institute5, University of Cologne6, University of Duisburg-Essen7, German Cancer Research Center8, Fox Chase Cancer Center9, Institut Gustave Roussy10, University of Zurich11, Princess Margaret Cancer Centre12, Johns Hopkins University13, Emory University14, Amgen15, New York University16, Washington University in St. Louis17
TL;DR: Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study as discussed by the authors, and particularly promising anti-cancer activity was observed i...
Abstract: Background Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed i...
571 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, Columbia University3, National Research University – Higher School of Economics4, Yale University5, University of Lagos6, Universidade Nova de Lisboa7, Institute for Fiscal Studies8, 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
Novo Nordisk1, German Cancer Research Center2, University of Zurich3, University of Barcelona4, Newcastle University5, Medical University of Vienna6, University of Tübingen7, University Hospital Heidelberg8, Weizmann Institute of Science9, Technische Universität München10, Max Planck Society11, Heidelberg University12, Icahn School of Medicine at Mount Sinai13, National and Kapodistrian University of Athens14, University of Turin15, University of Cambridge16, University of Florence17, Paris Diderot University18, Humanitas University19, Hannover Medical School20, University of Hamburg21, University of Mainz22, University of Düsseldorf23, Cornell University24, Memorial Sloan Kettering Cancer Center25, Harvard University26, University of Cologne27, Leibniz Association28, University of Bern29, Mount Sinai Hospital30, University of Texas MD Anderson Cancer Center31, Kindai University32, National Yang-Ming University33, Taipei Veterans General Hospital34, French Institute of Health and Medical Research35, University of Grenoble36, Imperial College London37, Catalan Institution for Research and Advanced Studies38
TL;DR: The progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers provides a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
Abstract: Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
TL;DR: In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection.
Abstract: More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals2,5–8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants. Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.
University of London1, University of Glasgow2, University of Edinburgh3, Lawrence Berkeley National Laboratory4, Memorial Sloan Kettering Cancer Center5, Cornell University6, University of Cambridge7, University of Lugano8, University of Zurich9, Maynooth University10, University of New South Wales11, ETH Zurich12, University of Liverpool13, Boston Children's Hospital14, National Institutes of Health15, Washington University in St. Louis16
TL;DR: In this paper, the authors demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K.
TL;DR: In this article, the authors investigated the persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale.
Abstract: BACKGROUND Waning of vaccine protection against SARS-CoV-2 infection or COVID-19 disease is a concern. This study investigated persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale. METHODS A matched test-negative, case-control study design was used to estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease, between January 1, 2021 to August 15, 2021. RESULTS Estimated BNT162b2 effectiveness against any infection, asymptomatic or symptomatic, was negligible for the first two weeks after the first dose, increased to 36.5% (95% CI: 33.1-39.8) in the third week after the first dose, and reached its peak at 72.1% (95% CI: 70.9-73.2) in the first five weeks after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating ≥15 weeks after the second dose, reaching diminished levels of protection by the 20th week. Effectiveness against symptomatic infection was higher than against asymptomatic infection, but still waned in the same fashion. Effectiveness against any severe, critical, or fatal disease increased rapidly to 67.7% (95% CI: 59.1-74.7) by the third week after the first dose, and reached 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose, where it persisted at about this level for six months. CONCLUSIONS BNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.
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.
Samsung Medical Center1, Peking University2, Cornell University3, Harvard University4, University of Montpellier5, Shanghai Jiao Tong University6, University of Ulsan7, Yonsei University8, Chang Gung University9, Prince of Songkla University10, Universidade Federal de Santa Maria11, Roswell Park Cancer Institute12, Kagawa University13, Merck & Co.14
TL;DR: In this paper, the authors compared pembrolizumab plus chemotherapy versus chemotherapy alone as a first-line treatment for advanced oesophageal cancer and Siewert type 1 gastro-oesophagesphageal junction cancer.
01 Mar 2021
TL;DR: In this article, the authors provide a review of federated learning in the biomedical space, and summarize the general solutions to the statistical challenges, system challenges, and privacy issues in federated Learning, and point out the implications and potentials in healthcare.
Abstract: With the rapid development of computer software and hardware technologies, more and more healthcare data are becoming readily available from clinical institutions, patients, insurance companies, and pharmaceutical industries, among others. This access provides an unprecedented opportunity for data science technologies to derive data-driven insights and improve the quality of care delivery. Healthcare data, however, are usually fragmented and private making it difficult to generate robust results across populations. For example, different hospitals own the electronic health records (EHR) of different patient populations and these records are difficult to share across hospitals because of their sensitive nature. This creates a big barrier for developing effective analytical approaches that are generalizable, which need diverse, "big data." Federated learning, a mechanism of training a shared global model with a central server while keeping all the sensitive data in local institutions where the data belong, provides great promise to connect the fragmented healthcare data sources with privacy-preservation. The goal of this survey is to provide a review for federated learning technologies, particularly within the biomedical space. In particular, we summarize the general solutions to the statistical challenges, system challenges, and privacy issues in federated learning, and point out the implications and potentials in healthcare.
University of California, San Francisco1, University of Michigan2, University of California, Davis3, University of Puerto Rico4, Cornell University5, University of Southern California6, Ponce Health Sciences University7, Cedars-Sinai Medical Center8, Georgetown University9, Fundación Instituto Leloir10, City of Hope National Medical Center11, Boston University12, National Institutes of Health13, St. Jude Children's Research Hospital14, LSU Health Sciences Center New Orleans15
TL;DR: To eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.
Abstract: There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA-African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.
TL;DR: The coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronav virus 2 (SARS-CoV-2) stimulated the development of highly effective vaccines that were produced with unprecedented speed with the use of diverse technologies, and certain findings were consistent across the three studies.
Abstract: The coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulated the development of highly effective vaccines that were produced wi...
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.
TL;DR: It is shown how the method for computing gravitational fine-grained entropy, developed over the past 15 years, can be extended to capture the entropy of Hawking radiation, and reveals large corrections needed for the entropy to be consistent with unitary black hole evaporation.
Abstract: In this review, recent progress on the black hole information problem that involves a new understanding of how to calculate the entropy of Hawking radiation is described. The review shows how the method for computing gravitational fine-grained entropy, developed over the past 15 years, can be extended to capture the entropy of Hawking radiation. This technique reveals large corrections needed for the entropy to be consistent with unitary black hole evaporation.
TL;DR: In this article, the authors studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.7 and B.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers.
Abstract: The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.
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 Michigan1, Cornell University2, University of Pennsylvania3, University of Massachusetts Medical School4, University of Naples Federico II5, Baylor College of Medicine6, Spanish National Research Council7, Complutense University of Madrid8, New York University9, University of Rome Tor Vergata10, Boston Children's Hospital11, NewYork–Presbyterian Hospital12, University of Pittsburgh13, French Institute of Health and Medical Research14, University of Paris15, National University of Cuyo16, Albert Einstein College of Medicine17, University of New Mexico18, Goethe University Frankfurt19, Weizmann Institute of Science20, University of Turku21, Sapienza University of Rome22, Virginia Commonwealth University23, St. Jude Children's Research Hospital24, Discovery Institute25, University of Copenhagen26, University of Tromsø27, Eötvös Loránd University28, Merck & Co.29, University of Freiburg30, Babraham Institute31, University of Adelaide32, University of South Australia33, University of Oviedo34, University of Chicago35, University of Graz36, National Institutes of Health37, City University of New York38, Queens College39, University of Tokyo40, University of Zurich41, Austrian Academy of Sciences42, University of British Columbia43, University of California, San Francisco44, Russian Academy of Sciences45, University Medical Center Groningen46, University of Cambridge47, University of Glasgow48, Rutgers University49, University of Padua50, Kazan Federal University51, University of Bern52, University of Oxford53, Oslo University Hospital54, University of Oslo55, Foundation for Research & Technology – Hellas56, University of Crete57, Francis Crick Institute58, Osaka University59, Harvard University60, Chinese Academy of Sciences61, Icahn School of Medicine at Mount Sinai62, Shanghai Jiao Tong University63, Karolinska Institutet64
TL;DR: In this paper, preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
Abstract: Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
20 Jun 2021
TL;DR: In this paper, the authors propose Neural Body, a new human body representation which assumes that learned neural representations at different frames share the same set of latent codes anchored to a deformable mesh, so that the observations across frames can be naturally integrated.
Abstract: This paper addresses the challenge of novel view synthesis for a human performer from a very sparse set of camera views. Some recent works have shown that learning implicit neural representations of 3D scenes achieves remarkable view synthesis quality given dense input views. However, the representation learning will be ill-posed if the views are highly sparse. To solve this ill-posed problem, our key idea is to integrate observations over video frames. To this end, we propose Neural Body, a new human body representation which assumes that the learned neural representations at different frames share the same set of latent codes anchored to a deformable mesh, so that the observations across frames can be naturally integrated. The deformable mesh also provides geometric guidance for the network to learn 3D representations more efficiently. To evaluate our approach, we create a multi-view dataset named ZJU-MoCap that captures performers with complex motions. Experiments on ZJU-MoCap show that our approach outperforms prior works by a large margin in terms of novel view synthesis quality. We also demonstrate the capability of our approach to reconstruct a moving person from a monocular video on the People-Snapshot dataset.
TL;DR: The memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response.
Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by five-fold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 4 months after coronavirus disease-2019 (COVID-19) onset, using immunofluorescence, or polymerase chain reaction, revealed persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
TL;DR: In this article, a multidisciplinary management approach is recommended for PDAC patients, which includes a multi-agent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil.
Abstract: Importance Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030. Observations Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86];P = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control. For patients with advanced (locally advanced and metastatic) PDAC, multiagent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil, all have a survival benefit of 2 to 6 months compared with a single-agent gemcitabine. For the 5% to 7% of patients with aBRCApathogenic germline variant and metastatic PDAC, olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, is a maintenance option that improves progression-free survival following initial platinum-based therapy. Conclusions and Relevance Approximately 60 000 new cases of PDAC are diagnosed per year, and approximately 50% of patients have advanced disease at diagnosis. The incidence of PDAC is increasing. Currently available cytotoxic therapies for advanced disease are modestly effective. For all patients, multidisciplinary management, comprehensive germline testing, and integrated supportive care are recommended.
Evgeny Epifanovsky, Andrew T.B. Gilbert1, Andrew T.B. Gilbert2, Xintian Feng3 +235 more•Institutions (54)
TL;DR: The Q-Chem quantum chemistry program package as discussed by the authors provides a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, and methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques.
Abstract: This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Seton Hall University5, Rutgers University6, University of Pennsylvania7, Cornell University8, Rush University Medical Center9, Anschutz Medical Campus10, Northwestern University11, Medical College of Wisconsin12, Rowan University13, Tufts University14, Thomas Jefferson University15, University of Queensland16, Ochsner Health System17, Johns Hopkins University18, New York University19, Indiana University – Purdue University Indianapolis20, ProMedica21, University of Vermont22, University of Miami23, Vanderbilt University24
TL;DR: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilzumab, and the findings may be susceptible to unmeasured confounding.
Abstract: Importance Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective To test whether tocilizumab decreases mortality in this population. Design, setting, and participants The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures Treatment with tocilizumab in the first 2 days of ICU admission. Main outcomes and measures Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of Conclusions and relevance Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.
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).