Showing papers by "University of California, Irvine published in 2021"
University of Nebraska Medical Center1, University of Texas Health Science Center at San Antonio2, Emory University3, National Institutes of Health4, Duke University5, University of California, Irvine6, University of Minnesota7, Cedars-Sinai Medical Center8, University of Florida9, Parkland Health & Hospital System10, University of California, San Diego11, Baylor College of Medicine12, University of Rochester13, Tan Tock Seng Hospital14, Scott & White Hospital15, University of California, San Francisco16, University of California, Davis17, University of Massachusetts Medical School18, University of Virginia19, Northwestern University20, Pennsylvania State University21, Providence Sacred Heart Medical Center and Children's Hospital22, University of Alabama at Birmingham23, Stanford University24, Denver Health Medical Center25, Seoul National University26, Changi General Hospital27, Kaiser Permanente28, Uniformed Services University of the Health Sciences29, Eli Lilly and Company30
TL;DR: Baricitinib plus remdesivir was superior to remdes Vivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation.
Abstract: Background Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. Results A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). Conclusions Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).
1,301 citations
TL;DR: In this article, a tool called CellChat is developed to quantitatively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data.
Abstract: Understanding global communications among cells requires accurate representation of cell-cell signaling links and effective systems-level analyses of those links. We construct a database of interactions among ligands, receptors and their cofactors that accurately represent known heteromeric molecular complexes. We then develop CellChat, a tool that is able to quantitatively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data. CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches. Through manifold learning and quantitative contrasts, CellChat classifies signaling pathways and delineates conserved and context-specific pathways across different datasets. Applying CellChat to mouse and human skin datasets shows its ability to extract complex signaling patterns. Our versatile and easy-to-use toolkit CellChat and a web-based Explorer ( http://www.cellchat.org/ ) will help discover novel intercellular communications and build cell-cell communication atlases in diverse tissues.
1,141 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
Manchester Metropolitan University1, National Oceanic and Atmospheric Administration2, University of Oxford3, German Aerospace Center4, Peking University5, Cooperative Institute for Research in Environmental Sciences6, University of Leeds7, National Center for Atmospheric Research8, Committee on Climate Change9, University of Michigan10, University of California, Irvine11, University of Reading12
TL;DR: CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone.
437 citations
TL;DR: In this article, the authors aim to answer four fundmental questions: 1) Why do we need RISs? 2) What is an RIS? 3] What are RIS's applications? 4) What are the relevant challenges and future research directions?
Abstract: Reconfigurable intelligent surfaces (RISs) or intelligent reflecting surfaces (IRSs) are regarded as one of the most promising and revolutionizing techniques for enhancing the spectrum and/ or energy efficiency of wireless systems. These devices are capable of reconfiguring the wireless propagation environment by carefully tuning the phase shifts of a large number of low-cost passive reflecting elements. In this article, we aim to answer four fundmental questions: 1) Why do we need RISs? 2) What is an RIS? 3) What are RIS's applications? 4) What are the relevant challenges and future research directions? In response, eight promising research directions are pointed out.
402 citations
North Carolina State University1, Ritsumeikan University2, Ohio State University3, University of California, Santa Barbara4, Institute of High Performance Computing Singapore5, Pohang University of Science and Technology6, University of California, Irvine7, University of California, Riverside8, Lawrence Berkeley National Laboratory9, Kyoto University10, Yanshan University11, Chinese Academy of Sciences12
Abstract: Heterostructured materials are an emerging class of materials with superior performances that are unattainable by their conventional homogeneous counterparts. They consist of heterogeneous zones wi...
392 citations
Niamh Mullins1, Andreas J. Forstner2, Andreas J. Forstner3, Andreas J. Forstner4 +396 more•Institutions (119)
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
378 citations
TL;DR: These guidelines are geared towards analyses performed with the open-source statistical software JASP, and most guidelines extend to Bayesian inference in general.
Abstract: Despite the increasing popularity of Bayesian inference in empirical research, few practical guidelines provide detailed recommendations for how to apply Bayesian procedures and interpret the results. Here we offer specific guidelines for four different stages of Bayesian statistical reasoning in a research setting: planning the analysis, executing the analysis, interpreting the results, and reporting the results. The guidelines for each stage are illustrated with a running example. Although the guidelines are geared towards analyses performed with the open-source statistical software JASP, most guidelines extend to Bayesian inference in general.
378 citations
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).
359 citations
TL;DR: In this article, the authors propose a method to detect context-shared and context-specific biological signals via accurate alignment using variance analysis in an unsupervised manner. But this method is limited to single-cell RNA-seq data.
Abstract: Distinguishing biological from technical variation is crucial when integrating and comparing single-cell genomics datasets across different experiments. Existing methods lack the capability in explicitly distinguishing these two variations, often leading to the removal of both variations. Here, we present an integration method scMC to remove the technical variation while preserving the intrinsic biological variation. scMC learns biological variation via variance analysis to subtract technical variation inferred in an unsupervised manner. Application of scMC to both simulated and real datasets from single-cell RNA-seq and ATAC-seq experiments demonstrates its capability of detecting context-shared and context-specific biological signals via accurate alignment.
322 citations
TL;DR: Concerns about rushed vaccine development appear to reduce vaccine uptake intent, as well as willingness to get the vaccine under EUA, and COVID-19 vaccine-related messages should address concerns about the vaccine and its development and reinforce benefits of the vaccine.
State University of New York Upstate Medical University1, Heidelberg University2, University of Melbourne3, Capital Medical University4, Harvard University5, Monash University, Clayton campus6, Icahn School of Medicine at Mount Sinai7, Montreal Children's Hospital8, Universidade Federal do Rio Grande do Sul9, Peking University10, University of Southampton11, University of Toronto12, University of Washington13, King Khalid University14, King's College London15, Aga Khan University16, Karolinska Institutet17, Radboud University Nijmegen18, Vrije Universiteit Brussel19, University of Nottingham20, Aarhus University21, University of Cologne22, Trinity College, Dublin23, University of Würzburg24, University of Bergen25, University Medical Center Groningen26, University of Wyoming27, University of California, Berkeley28, University of California, San Francisco29, Nottinghamshire Healthcare NHS Foundation Trust30, Duke University31, University of Amsterdam32, Örebro University33, Chongqing Medical University34, Tel Aviv University35, Washington University in St. Louis36, Federal University of Rio de Janeiro37, University College Cork38, University of British Columbia39, University of Pittsburgh40, Oregon Health & Science University41, University of Montpellier42, University of Ibadan43, University of São Paulo44, Hebrew University of Jerusalem45, University of Sydney46, Jawaharlal Institute of Postgraduate Medical Education and Research47, University of Canterbury48, Autonomous University of Barcelona49, Stellenbosch University50, University of California, Davis51, National Medical College52, Hofstra University53, University of Texas Health Science Center at Houston54, University of Southern Denmark55, University of California, Irvine56, Cardiff University57, Okinawa Institute of Science and Technology58, HU University of Applied Sciences Utrecht59, Katholieke Universiteit Leuven60, University of the Free State61, Johns Hopkins University62, University of Turin63, University of Zurich64
TL;DR: In this article, the authors presented 208 empirically supported statements about ADHD using meta-analysis, which allow for firm statements about the nature, course, outcome causes and treatments for disorders that are useful for reducing misconceptions and stigma.
Mayo Clinic1, Harvard University2, Roswell Park Cancer Institute3, University of California, Irvine4, University of Wisconsin–Milwaukee5, Rutgers University6, City of Hope National Medical Center7, Boston University8, University of Wisconsin-Madison9, American Cancer Society10, University of Southern California11, University of Oxford12, Stanford University13, Fred Hutchinson Cancer Research Center14, University of Washington15, National Institutes of Health16, Vanderbilt University17, Cornell University18, University of Utah19, University of Pennsylvania20
TL;DR: In this paper, population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and risk assessment.
Abstract: Background Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and...
University of New South Wales1, Max Planck Society2, Netherlands Environmental Assessment Agency3, University of Natural Resources and Life Sciences, Vienna4, Technical University of Dortmund5, Imperial College London6, University of Bristol7, International Institute for Applied Systems Analysis8, Copenhagen Business School9, University of Groningen10, University of Maryland, College Park11, Federal University of Rio de Janeiro12, Lawrence Berkeley National Laboratory13, Great Zimbabwe University14, University of California, Irvine15, Peking University16, Asian Institute of Technology17, Chinese Academy of Sciences18, Shanghai Jiao Tong University19
TL;DR: In this paper, the authors present estimates of greenhouse gas emissions trends by sector from 1990 to 2018, describing the major sources of emissions growth, stability and decline across ten global regions.
Abstract: Global greenhouse gas emissions can be traced to five economic sectors: energy, industry, buildings, transport and AFOLU (agriculture, forestry and other land uses). In this topical review we synthesize the literature to explain recent trends in global and regional emissions in each of these sectors. To contextualise our review, we present estimates of greenhouse gas emissions trends by sector from 1990 to 2018, describing the major sources of emissions growth, stability and decline across ten global regions. Both the literature and data emphasize limited progress towards reducing greenhouse gas emissions. The prominent global pattern is a continuation of underlying drivers with few signs of emerging limits to demand, nor of a deep shift towards the delivery of low and zero carbon services across sectors. We observe a moderate decarbonisation of energy systems in Europe and North America, driven by fuel switching and the increasing penetration of renewables. By contrast, in rapidly industrialising regions, fossil-based energy systems have continuously expanded, only very recently slowing down in their growth. Strong demand for materials, floor area, energy services and travel have driven emissions growth in the industry, buildings and transport sectors, particularly in Eastern Asia, Southern Asia and South-East Asia. An expansion of agriculture into carbon-dense tropical forest areas has driven recent increases in AFOLU emissions in Latin America, South-East Asia and Africa. Identifying, understanding, and tackling the most persistent and climate-damaging trends across sectors is a fundamental concern for research and policy as humanity treads deeper into the Anthropocene.
TL;DR: In this article, the authors study the US public's health behaviors, attitudes, and policy opinions about COVID-19 in the earliest weeks of the national health crisis (March 20-23, 2020) and find that partisanship-measured as party identification, support for President Trump, or left right ideological positioning-explains differences in Americans across a wide range of health behaviors and policy preferences.
Abstract: Objective To study the US public's health behaviors, attitudes, and policy opinions about COVID-19 in the earliest weeks of the national health crisis (March 20-23, 2020) Method We designed and fielded an original representative survey of 3,000 American adults between March 20-23, 2020 to collect data on a battery of 38 health-related behaviors, government policy preferences on COVID-19 response and worries about the pandemic We test for partisan differences COVID-19 related policy attitudes and behaviors, measured in three different ways: party affiliation, intended 2020 Presidential vote, and self-placed ideological positioning Our multivariate approach adjusts for a wide range of individual demographic and geographic characteristics that might confound the relationship between partisanship and health behaviors, attitudes, and preferences Results We find that partisanship-measured as party identification, support for President Trump, or left-right ideological positioning-explains differences in Americans across a wide range of health behaviors and policy preferences We find no consistent evidence that controlling for individual news consumption, the local policy environment, and local pandemic-related deaths erases the observed partisan differences in health behaviors, beliefs, and attitudes In further analyses, we use a LASSO regression approach to select predictors, and find that a partisanship indicator is the most commonly selected predictor across the 38 dependent variables that we study Conclusion Our analysis of individual self-reported behavior, attitudes, and policy preferences in response to COVID-19 reveals that partisanship played a central role in shaping individual responses in the earliest months of the COVID-19 pandemic These results indicate that partisan differences in responding to a national public health emergency were entrenched from the earliest days of the pandemic
TL;DR: In this paper, it was shown that Fe-N-C catalysts initially comprising two distinct FeNx sites (S1 and S2) degrade via the transformation of S1 into iron oxides while the structure and number of S2 were unmodified.
Abstract: While Fe-N-C materials are a promising alternative to platinum for catalyzing oxygen reduction in acidic polymer fuel cells, limited understanding of their operando degradation restricts rational approaches towards improved durability. Here we show that Fe-N-C catalysts initially comprising two distinct FeNx sites (S1 and S2) degrade via the transformation of S1 into iron oxides while the structure and number of S2 were unmodified. Structure-activity correlations drawn from end-of-test 57Fe Mossbauer spectroscopy reveal that both sites initially contribute to the ORR activity but only S2 significantly contributes after 50 h of operation. From in situ 57Fe Mossbauer spectroscopy in inert gas coupled to calculations of the Mossbauer signature of FeNx moieties in different electronic states, we identify S1 to be a high-spin FeN4C12 moiety and S2 a low- or intermediate spin FeN4C10 moiety. These insights lay the ground for rational approaches towards Fe-N-C cathodes with improved durability in acidic fuel cells.
Katholieke Universiteit Leuven1, Sapienza University of Rome2, University of Paris3, University of Toulouse4, Boston Children's Hospital5, Harvard University6, University of California, Irvine7, University of Brescia8, Vita-Salute San Raffaele University9, Erasmus University Medical Center10, Hospital Clínico San Carlos11, Complutense University of Madrid12, Epsom and St Helier University Hospitals NHS Trust13, National Institutes of Health14, University of São Paulo15, University of Padua16, University of Naples Federico II17, Ghent University18, Nationwide Children's Hospital19, Marmara University20, Newcastle University21, University Hospital of Wales22, Universidad del Desarrollo23, Saint Louis University Hospital24, Ludwig Maximilian University of Munich25, Icahn School of Medicine at Mount Sinai26, University of Freiburg27, Children's Hospital of Philadelphia28, Garvan Institute of Medical Research29, University of New South Wales30
TL;DR: More than 30% of patients with IEI with SARS-CoV-2 infection had mild coronavirus disease 2019 (COVID-19) and risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients withIEI, including more younger patients.
Abstract: Background There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. Conclusions This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.
01 Mar 2021
TL;DR: In this article, the authors demonstrate that Cu single atoms incorporated in graphitic carbon nitride can catalytically activate H2O2 to generate hydroxyl radicals at pH 7.0 without energy input.
Abstract: The presence of organic contaminants in wastewater poses considerable risks to the health of both humans and ecosystems. Although advanced oxidation processes that rely on highly reactive radicals to destroy organic contaminants are appealing treatment options, substantial energy and chemical inputs limit their practical applications. Here we demonstrate that Cu single atoms incorporated in graphitic carbon nitride can catalytically activate H2O2 to generate hydroxyl radicals at pH 7.0 without energy input, and show robust stability within a filtration device. We further design an electrolysis reactor for the on-site generation of H2O2 from air, water and renewable energy. Coupling the single-atom catalytic filter and the H2O2 electrolytic generator in tandem delivers a wastewater treatment system. These findings provide a promising path toward reducing the energy and chemical demands of advanced oxidation processes, as well as enabling their implementation in remote areas and isolated communities.
Oak Ridge National Laboratory1, University of New South Wales2, Ludwig Maximilian University of Munich3, University of Arizona4, Stanford University5, Scripps Institution of Oceanography6, Smithsonian Environmental Research Center7, University of Sydney8, Max Planck Society9, Smithsonian Tropical Research Institute10, Smithsonian Conservation Biology Institute11, Seconda Università degli Studi di Napoli12, University of Leeds13, Swiss Federal Institute for Forest, Snow and Landscape Research14, Aix-Marseille University15, University of California, Santa Barbara16, Commonwealth Scientific and Industrial Research Organisation17, Université Paris-Saclay18, Australian National University19, National University of Singapore20, ETH Zurich21, California Institute of Technology22, Imperial College London23, Northern Arizona University24, Oeschger Centre for Climate Change Research25, University of California, Berkeley26, Lawrence Berkeley National Laboratory27, University of Basel28, Auckland University of Technology29, Indiana University30, University of Oxford31, Spanish National Research Council32, Umeå University33, University of Exeter34, Lawrence Livermore National Laboratory35, University of California, Irvine36, United States Geological Survey37, State University of New York College of Environmental Science and Forestry38, Rutgers University39, Wageningen University and Research Centre40
TL;DR: A range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
Abstract: Atmospheric carbon dioxide concentration ([CO2 ]) is increasing, which increases leaf-scale photosynthesis and intrinsic water-use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO2 ] increase and thus climate change. However, ecosystem CO2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO2 ]-driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO2 ] (iCO2 ) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre-industrial times. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2 , albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
Washington University in St. Louis1, Vanderbilt University2, University of California, San Francisco3, University of Washington4, University of Chicago5, University of California, San Diego6, University of Rochester7, Emory University8, Mayo Clinic9, University of Maryland, College Park10, University of California, Los Angeles11, Memorial Sloan Kettering Cancer Center12, Ludwig Maximilian University of Munich13, University of California, Davis14, Utrecht University15, University of Texas MD Anderson Cancer Center16, Harvard University17, Loyola University Chicago18, University of California, Irvine19, University of Rennes20
TL;DR: The pivotal phase 2 results of ZUMA-3, an international, multicentre, single-arm, open-label study evaluating the efficacy and safety of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia remain poor, underlining the need for more effective therapies.
TL;DR: The studies reviewed in this article confirm that stress has an impact on multiple biological systems and ought to consider further the importance of early-life adversity and continue to explore how different biological systems interact in the context of stress and health processes.
Abstract: The cumulative science linking stress to negative health outcomes is vast. Stress can affect health directly, through autonomic and neuroendocrine responses, but also indirectly, through changes in health behaviors. In this review, we present a brief overview of (a) why we should be interested in stress in the context of health; (b) the stress response and allostatic load; (c) some of the key biological mechanisms through which stress impacts health, such as by influencing hypothalamic-pituitary-adrenal axis regulation and cortisol dynamics, the autonomic nervous system, and gene expression; and (d) evidence of the clinical relevance of stress, exemplified through the risk of infectious diseases. The studies reviewed in this article confirm that stress has an impact on multiple biological systems. Future work ought to consider further the importance of early-life adversity and continue to explore how different biological systems interact in the context of stress and health processes.
Stephen P.H. Alexander1, Arthur Christopoulos2, Anthony P. Davenport3, Eamonn Kelly4 +151 more•Institutions (85)
TL;DR: The Concise Guide to PHARMACOLOGY 2021/22 as mentioned in this paper provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands.
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
TL;DR: In this paper, the virology and immunology of SARS-CoV-2, alternative therapies for COVID-19 to vaccination, principles and design considerations in vaccine development, and the promises and roles of vaccine carriers in addressing the unique immunopathological challenges presented by the disease.
TL;DR: In this paper, the authors identify common barriers and facilitators that influence user engagement with digital mental health interventions (DMHIs), which deliver mental health support via technologies such as mobile apps, and many studies have demonstrated their effectiveness in improving symptoms.
Abstract: Background: Digital mental health interventions (DMHIs), which deliver mental health support via technologies such as mobile apps, can increase access to mental health support, and many studies have demonstrated their effectiveness in improving symptoms. However, user engagement varies, with regard to a user’s uptake and sustained interactions with these interventions.
Objective: This systematic review aims to identify common barriers and facilitators that influence user engagement with DMHIs.
Methods: A systematic search was conducted in the SCOPUS, PubMed, PsycINFO, Web of Science, and Cochrane Library databases. Empirical studies that report qualitative and/or quantitative data were included.
Results: A total of 208 articles met the inclusion criteria. The included articles used a variety of methodologies, including interviews, surveys, focus groups, workshops, field studies, and analysis of user reviews. Factors extracted for coding were related to the end user, the program or content offered by the intervention, and the technology and implementation environment. Common barriers included severe mental health issues that hampered engagement, technical issues, and a lack of personalization. Common facilitators were social connectedness facilitated by the intervention, increased insight into health, and a feeling of being in control of one’s own health.
Conclusions: Although previous research suggests that DMHIs can be useful in supporting mental health, contextual factors are important determinants of whether users actually engage with these interventions. The factors identified in this review can provide guidance when evaluating DMHIs to help explain and understand user engagement and can inform the design and development of new digital interventions.
Trial Registration:
TL;DR: The mortality rate is used as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases and indicates that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases.
Stanford University1, National Institutes of Health2, Mayo Clinic3, University of Western Ontario4, Harvard University5, Baylor College of Medicine6, University of Oxford7, Genentech8, University of Cambridge9, Johns Hopkins University10, Fred Hutchinson Cancer Research Center11, University of California, Irvine12, National Institute for Health Research13, European Bioinformatics Institute14, University of North Carolina at Chapel Hill15, Centers for Disease Control and Prevention16, Emory University17, Kaiser Permanente18
TL;DR: The Polygenic Risk Score Reporting Standards (PRS-RS) as discussed by the authors is a comprehensive reporting framework that defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications.
Abstract: Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.
TL;DR: In this article, the authors highlight the basic engineering principles of common wearable sensors and where they can be error-prone and examine the role of these devices in the remote screening and diagnosis of common cardiovascular diseases, such as arrhythmias, and in the management of patients with established cardiovascular conditions, for example, heart failure.
Abstract: Technological innovations reach deeply into our daily lives and an emerging trend supports the use of commercial smart wearable devices to manage health. In the era of remote, decentralized and increasingly personalized patient care, catalysed by the COVID-19 pandemic, the cardiovascular community must familiarize itself with the wearable technologies on the market and their wide range of clinical applications. In this Review, we highlight the basic engineering principles of common wearable sensors and where they can be error-prone. We also examine the role of these devices in the remote screening and diagnosis of common cardiovascular diseases, such as arrhythmias, and in the management of patients with established cardiovascular conditions, for example, heart failure. To date, challenges such as device accuracy, clinical validity, a lack of standardized regulatory policies and concerns for patient privacy are still hindering the widespread adoption of smart wearable technologies in clinical practice. We present several recommendations to navigate these challenges and propose a simple and practical 'ABCD' guide for clinicians, personalized to their specific practice needs, to accelerate the integration of these devices into the clinical workflow for optimal patient care.
TL;DR: It is demonstrated that primary mouse and human hepatocytes can undergo pyroptosis upon NLRP3 inflammasome activation with subsequent release of NLRP1-YFP HEK cells that amplify and perpetuate inflammaome-driven fibrogenesis.
Beth Israel Deaconess Medical Center1, Northwestern University2, Technische Universität München3, University of Düsseldorf4, University of Paris5, University of Tsukuba6, Genentech7, Fred Hutchinson Cancer Research Center8, University of California, Los Angeles9, University of Chicago10, Memorial Sloan Kettering Cancer Center11, Fox Chase Cancer Center12, Yale Cancer Center13, Johns Hopkins University14, University of Tübingen15, University of California, Irvine16, University of Iowa17, Netherlands Cancer Institute18, Cornell University19, St Bartholomew's Hospital20
TL;DR: The IMvigor010 trial as discussed by the authors evaluated atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma.
Abstract: Summary Background Despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and no level 1 evidence for adjuvant therapy. We aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma. Method In the IMvigor010 study, a multicentre, open-label, randomised, phase 3 trial done in 192 hospitals, academic centres, and community oncology practices across 24 countries or regions, patients aged 18 years and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2–4a or ypN+ tumours following neoadjuvant chemotherapy or pT3–4a or pN+ tumours if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy must have been ineligible for or declined cisplatin-based adjuvant chemotherapy. No post-surgical radiotherapy or previous adjuvant chemotherapy was allowed. Patients were randomly assigned (1:1) using a permuted block (block size of four) method and interactive voice-web response system to receive 1200 mg atezolizumab given intravenously every 3 weeks for 16 cycles or up to 1 year, whichever occurred first, or to observation. Randomisation was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumour stage, and PD-L1 expression on tumour-infiltrating immune cells. The primary endpoint was disease-free survival in the intention-to-treat population. Safety was assessed in patients who either received at least one dose of atezolizumab or had at least one post-baseline safety assessment. This trial is registered with ClinicalTrials.gov, NCT02450331, and is ongoing but not recruiting patients. Findings Between Oct 5, 2015, and July 30, 2018, we enrolled 809 patients, of whom 406 were assigned to the atezolizumab group and 403 were assigned to the observation group. Median follow-up was 21·9 months (IQR 13·2–29·8). Median disease-free survival was 19·4 months (95% CI 15·9–24·8) with atezolizumab and 16·6 months (11·2–24·8) with observation (stratified hazard ratio 0·89 [95% CI 0·74–1·08]; p=0·24). The most common grade 3 or 4 adverse events were urinary tract infection (31 [8%] of 390 patients in the atezolizumab group vs 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) vs 14 [4%]), and anaemia (eight [2%] vs seven [2%]). Serious adverse events occurred in 122 (31%) patients who received atezolizumab and 71 (18%) who underwent observation. 63 (16%) patients who received atezolizumab had a treatment-related grade 3 or 4 adverse event. One treatment-related death, due to acute respiratory distress syndrome, occurred in the atezolizumab group. Interpretation To our knowledge, IMvigor010 is the largest, first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time. Funding F Hoffmann-La Roche/Genentech.
TL;DR: Directed energy deposition (DED) is a branch of additive manufacturing (AM) processes in which a feedstock material in the form of powder or wire is delivered to a substrate on which an energy source such as laser beam, electron beam, or plasma/electric arc is simultaneously focused, thus forming a small melt pool and continuously depositing material, layer by layer as discussed by the authors.