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Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information (vol 91, pg 626, 2022)

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biological PSYCHIATRY 2022年第7期91卷 690-690页

作者： Maihofer, Adam X. Vinkers, Christiaan H. Department of Psychiatry University of California San Diego La Jolla California Department of Family Medicine and Public Health University of California San Diego La Jolla California Center of Excellence for Stress and Mental Health Veterans Affairs Healthcare System San Diego California. Electronic address: amaihofer@health.ucsd.edu. Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts Department of Psychiatry Massachusetts General Hospital Boston Massachusetts. Social Genetic and Developmental Psychiatry Centre Institute of Psychiatry Psychology and Neuroscience King's College London London United Kingdom National Institute of Health Research Maudsley Biomedical Research Centre King's College London London United Kingdom. Department of Psychiatry Harvard Medical School Boston Massachusetts Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts Center of Excellence in Depression and Anxiety Disorders Belmont Massachusetts. Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts. Department of Psychiatry University of California San Diego La Jolla California Center of Excellence for Stress and Mental Health Veterans Affairs Healthcare System San Diego California Research Service Veterans Affairs Healthcare System San Diego California. Duke Molecular Physiology Institute Duke University School of Medicine Durham North Carolina. Department of Psychiatry Veterans Affairs Connecticut Healthcare System West Haven Connecticut Department of Psychiatry Yale University School of Medicine New Haven Connecticut. Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts Department of Epidemiology Columbia University Mailman School of Public Health New York. Division of Mental Health Atlanta Veterans Affairs Medical Center

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

关键词： GWAS Genetics Heritability PTSD PheWAS Trauma

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623 - Topical steroid withdrawal is a targetable overproduction of nicotinic acid from mitochondrial complex I overexpression

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British Journal of Dermatology 2024年第SUPPLEMENT_2期191卷

作者： Shobnam, Nadia Ratley, Grace Saksena, Sarini Yadav, Manoj Chaudhary, Prem Prashant Sun, Ashleigh A Howe, Katherine N Gadkari, Manasi Franco, Luis M Ganesan, Sundar McCann, Katelyn J Hsu, Amy P Kanakabandi, Kishore Ricklefs, Stacy Lack, Justin Yu, Weiming Similuk, Morgan Walkiewicz, Magdalena A for the NIAID Centralized Sequencing program Gardner, Donna D Barta, Kelly Tullos, Kathryn Myles, Ian A Laboratory of Clinical Immunology and Microbiology (LCIM) Epithelial Therapeutics Unit National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Bethesda MD USA LCIM NIAID NIH Bethesda MD USA Functional Immunogenomics Section Systemic Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH Bethesda MD USA Biological Imaging Section Research Technology Branch NIAID NIH Bethesda MD USA Genomic Research Section Research Technologies Branch (RTB) Rocky Mountain Laboratories NIAID NIH Hamilton MT USA Integrated Data Science Section RTB NIAID NIH Bethesda MD USA Lymphocyte Biology Section Laboratory of Immune System Biology NIAID NIH Bethesda MD USA Centralized Sequencing Program Division of Intramural Research NIAID Bethesda MD USA Allergy & Asthma Network Fairfax VA USA International Topical Steroid Awareness Network Dacula GA USA

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Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters

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Npj viruses 2025年第1期3卷 15页

作者： Andra Banete Bryan D Griffin Juan C Corredor Emily Chien Lily Yip Tarini N A Gunawardena Kuganya Nirmalarajah Jady Liang Yaejin Lee Alexander Leacy Sara Pagliarani Richard de Borja Winfield Yim Hunsang Lee Yu Onodera Patryk Aftanas Patrick Budylowski Sang Kyun Ahn Yanlong Pei Hong Ouyang Laura Kent Xinliu Angel Li Mario A Ostrowski Robert A Kozak Sarah K Wootton Natasha Christie-Holmes Scott D Gray-Owen Mikko Taipale Jared T Simpson Finlay Maguire Allison J McGeer Haibo Zhang Leonardo Susta Theo J Moraes Samira Mubareka Biological Sciences Sunnybrook Research Institute Toronto ON Canada. Program in Molecular Medicine The Hospital for Sick Children Toronto ON Canada. Program in Translational Medicine Hospital for Sick Children Toronto ON Canada. Keenan Research Centre for Biomedical Science St. Michael's Hospital Unity Health Toronto Toronto ON Canada. Department of Physiology University of Toronto Toronto ON Canada. Department of Pathobiology University of Guelph Guelph ON Canada. Ontario Institute for Cancer Research Toronto ON Canada. Donnelly Centre for Cellular and Biomolecular Research University of Toronto Toronto ON Canada. Department of Emergency and Critical Care Medicine Faculty of Medicine Yamagata University Yamagata Japan. Shared Hospital Laboratory Toronto ON Canada. Department of Medicine University of Toronto Toronto ON Canada. Institute of Medical Science University of Toronto Toronto ON Canada. Department of Molecular Genetics University of Toronto Toronto ON Canada. Division of Comparative Medicine Faculty of Medicine University of Toronto Toronto ON Canada. Department of Microbiology Sinai Health System Toronto ON Canada. Department of Immunology University of Toronto Toronto ON Canada. Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada. Toronto High Containment Facility Temerty Faculty of Medicine University of Toronto Toronto ON Canada. Department of Computer Science University of Toronto Toronto ON Canada. Department of Community Health and Epidemiology Faculty of Medicine Dalhousie University Halifax NS Canada. Faculty of Computer Science Dalhousie University Halifax NS Canada. Interdepartmental Division of Critical Care Medicine University of Toronto Toronto ON Canada. Department of Anaesthesiology and Pain Medicine University of Toronto Toronto ON Canada. Division of Respiratory Medicine Department of Pediatrics Hospital for Sick Children Toronto ON Canada. Biological

Since the emergence of SARS-CoV-2 in humans, novel variants have evolved to become dominant circulating lineages. These include D614G (B.1 lineage), Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2), and Omicron BA.1 (B.1.1.529) and BA.2 (B.1.1.529.2) viruses. Here, we compared the viral replication, pathogenesis, and transmissibility of these variants. Replication kinetics and innate immune response against the viruses were tested in ex vivo human nasal epithelial cells (HNEC) and induced pluripotent stem cell-derived lung organoids (IPSC-LOs), and the golden hamster model was employed to test pathogenicity and potential for transmission by the respiratory route. Delta, BA.1, and BA.2 viruses replicated more efficiently, and outcompeted D614G, Alpha, and Gamma viruses in an HNEC competition assay. BA.1 and BA.2 viruses, however, replicated poorly in IPSC-LOs compared to other variants. Moreover, BA.2 virus infection significantly increased secretion of IFN-λ1, IFN-λ2, IFN-λ3, IL-6, and IL-1RA in HNECs relative to D614G infection, but not in IPSC-LOs. The BA.1 and BA.2 viruses replicated less effectively in hamster lungs compared to the other variants; and while the Gamma virus reached titers comparable to D614G and Delta viruses, it caused greater lung pathology. Lastly, the Gamma and Delta variants transmitted more efficiently by the respiratory route compared to the other viruses, while BA.1 and BA.2 viruses transmitted less efficiently. These findings demonstrate the ongoing utility of experimental risk assessment as SARS-CoV-2 variants continue to evolve.

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Nitrogen and phosphorus constrain the CO2 fertilization of global plant biomass (vol 21, pg 561, 2020)

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NATURE CLIMATE CHANGE 2020年第7期10卷 696-697页

作者： Terrer, Cesar Jackson, Robert B. Prentice, I. Colin Keenan, Trevor F. Kaiser, Christina Vicca, Sara Fisher, Joshua B. Reich, Peter B. Stocker, Benjamin D. Hungate, Bruce A. Penuelas, Josep McCallum, Ian Soudzilovskaia, Nadejda A. Cernusak, Lucas A. Talhelm, Alan F. Van Sundert, Kevin Piao, Shilong Newton, Paul C. D. Hovenden, Mark J. Blumenthal, Dana M. Liu, Yi Y. Mueller, Christoph Winter, Klaus Field, Christopher B. Viechtbauer, Wolfgang Van Lissa, Caspar J. Hoosbeek, Marcel R. Watanabe, Makoto Koike, Takayoshi Leshyk, Victor O. Polley, H. Wayne Franklin, Oskar Department of Earth System Science Stanford University Stanford USA Institut de Ciència i Tecnologia Ambientals Universitat Autònoma de Barcelona Barcelona Spain Ecosystems Services and Management Program International Institute for Applied Systems Analysis Laxenburg Austria Woods Institute for the Environment and Precourt Institute for Energy Stanford University Stanford USA AXA Chair Programme in Biosphere and Climate Impacts Department of Life Sciences Imperial College London Silwood Park Campus Ascot UK Department of Biological Sciences Macquarie University North Ryde Australia Department of Earth System Science Tsinghua University Beijing China Department of Environmental Science Policy and Management UC Berkeley Berkeley USA Climate and Ecosystem Sciences Division Lawrence Berkeley National Laboratory Berkeley USA Department of Microbiology and Ecosystem Science Division of Terrestrial Ecosystem Research Faculty of Life Sciences University of Vienna Vienna Austria Evolution and Ecology Program International Institute for Applied Systems Analysis Laxenburg Austria Centre of Excellence PLECO (Plants and Ecosystems) Biology Department University of Antwerp Wilrijk Belgium Jet Propulsion Laboratory California Institute of Technology Pasadena USA Joint Institute for Regional Earth System Science and Engineering University of California at Los Angeles Los Angeles USA Department of Forest Resources University of Minnesota St. Paul USA Hawkesbury Institute for the Environment Western Sydney University Penrith Australia CREAF Cerdanyola del Vallès Spain Center for Ecosystem Science and Society Northern Arizona University Flagstaff USA Department of Biological Sciences Northern Arizona University Flagstaff USA CSIC Global Ecology Unit CREAF-CEAB-UAB Bellaterra Spain Environmental Biology Department Institute of Environmental Sciences Leiden University Leiden the Netherlands College of Marine and Environmental Sciences James Cook University Cairns

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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INTRODUCTION

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Bulletin of the American Meteorological Society 2024年第8期105卷 S1-S11页

作者： Boyer, T. Blunden, J. Dunn, R.J.H. NOAA/NESDIS National Centers for Environmental Information Silver Spring Maryland NOAA/NESDIS National Centers for Environmental Information Asheville North Carolina Met Office Hadley Centre Exeter United Kingdom European Centre for Medium-Range Weather Forecasts Reading United Kingdom University of Maryland College Park Maryland Scripps Institution of Oceanography University of California San Diego La Jolla California NOAA/NWS National Centers for Environmental Prediction Climate Prediction Center College Park Maryland Brandenburg University of Technology (BTU) Cottbus-Senftenberg Germany Servicio Meteorológico Nacional Buenos Aires Argentina NOAA/OAR Physical Sciences Laboratory Boulder Colorado European Centre for Medium-Range Weather Forecasts Bonn Germany Center for Geophysical Research and School of Physics University of Costa Rica San José Costa Rica Department of Meteorology and National Centre for Earth Observation University of Reading Reading United Kingdom Centro Nacional de Monitoramento e Alertas de Desastres Naturais CEMADEN São Paulo Brazil Université Grenoble Alpes Institut des Géosciences de l’Environnement IRD CNRS Grenoble INP Grenoble France Hampton University Hampton Virginia Seychelles Meteorological Authority Mahe Seychelles Section for Glaciers Ice and Snow Norwegian Water Resources and Energy Directorate Oslo Norway National Research Institute for Agriculture Food and Environment (INRAE) CARRTEL Université Savoie Mont Blanc Thonon les Bains France Graduate School of Agriculture Osaka Metropolitan University Sakai Japan Science Faculty Universidad Nacional de Colombia Bogotá Colombia University of Bremen Bremen Germany NOAA Global Monitoring Laboratory Boulder Colorado Servicio Nacional de Meteorología e Hidrología del Perú Lima Perú Centro de Investigaciones sobre Desertificación – Spanish National Research Council (CSIC-UV-GVA) Valencia Spain Hydro-Climate Extremes Lab (H-CEL) Ghent University Ghent Belgium Department o

In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. A

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Obesity alters pathology and treatment response in inflammatory disease

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四川生理科学杂志 2022年第3期44卷 446-446页

作者： Sagar P Bapat NOMIS Center for Immunobiology and Microbial Pathogenesis The Salk Institute for Biological Studies La Jolla CA USA Gene Expression Laboratory The Salk Institute for Biological Studies La Jolla CA USA Medical Scientist Training Program University of California San Diego La Jolla CA USA Department of Laboratory Medicine University of California San Francisco San Francisco CA USA Department of Microbiology and Immunology University of California San Francisco San Francisco CA USA Diabetes Center University of California San Francisco San Francisco CA USA Medical Scientist Training Program University of California San Francisco CA USA Division of Pulmonary Critical Care Allergy and Sleep Department of Medicine University of California San Francisco San Francisco CA USA School of Pharmaceutical Sciences Xiamen University Xiamen China Department of Dermatology University of California San Diego La Jolla CA USA Department of Surgery University of California San Francisco San Francisco CA USA Department of Medicine University of California San Francisco San Francisco CA USA Sandler Asthma Basic Research Center University of California San Francisco San Francisco CA USA School of Medicine Wake Forest University Winston–Salem NC USA Department of Dermatology Icahn School of Medicine at Mount Sinai New York NY USA Lung Biology Center Department of Medicine University of California San Francisco San Francisco CA USA Department of Biomedical Science Graduate School Kyungpook National University Kyungpook National University Hospital Daegu South Korea Department of Dermatology University of California San Francisco San Francisco CA USA Department of Pathology University of California San Francisco San Francisco CA USA Department of Internal Medicine Division of Pulmonary Critical Care and Sleep Medicine University of Kentucky Lexington KY USA Pulmonary Critical Care Section Department of Medicine Veterans Affairs San Diego Hea

Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune,allergic and inflammatory *** evidence indicates that obesity and metabolic disease can also influence the immune system1-7,although the mechanisms and effects on immunotherapy outcomes remain largely ***,using two models of atopic dermatitis,we show that lean and obese mice mount markedly different immune *** converted the classical type 2 T helper(TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 *** also observed divergent responses to biologic therapies targeting TH2 cytokines,which robustly protected lean mice but exacerbated disease in obese ***-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ(PPARγ)in TH2 cells from obese mice relative to lean mice.

关键词： dermatitis inflammatory allergic

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TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A (vol 603, pg 131, 2022)

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NATURE 2024年第8020期631卷 E7-E7页

作者： Brown, Anna-Leigh Wilkins, Oscar G. Keuss, Matthew J. Hill, Sarah E. Zanovello, Matteo Lee, Weaverly Colleen Bampton, Alexander Lee, Flora C. Y. Masino, Laura Qi, Yue A. Bryce-Smith, Sam Gatt, Ariana Hallegger, Martina Fagegaltier, Delphine Phatnani, Hemali Phatnani, Hemali Newcombe, Jia Gustavsson, Emil K. Seddighi, Sahba Reyes, Joel F. Coon, Steven L. Ramos, Daniel Schiavo, Giampietro Fisher, Elizabeth M. C. Raj, Towfique Secrier, Maria Lashley, Tammaryn Ule, Jernej Buratti, Emanuele Humphrey, Jack Ward, Michael E. Fratta, Pietro UCL Queen Square Motor Neuron Disease Centre Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology UCL London UK The Francis Crick Institute London UK UK Dementia Research Institute University College London London UK Department of Molecular Biology and Nanobiotechnology National Institute of Chemistry Ljubljana Slovenia National Institute of Neurological Disorders and Stroke NIH Bethesda MD USA Medical Scientist Training Program Johns Hopkins University School of Medicine Baltimore MD USA Center for Alzheimer’s and Related Dementias National Institutes of Health Bethesda MD USA Queen Square Brain Bank UCL Queen Square Institute of Neurology University College London London UK Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology University College London London UK Great Ormond Street Institute of Child Health Genetics and Genomic Medicine University College London London UK Center for Genomics of Neurodegenerative Disease New York Genome Center (NYGC) New York NY USA NeuroResource Department of Neuroinflammation UCL Queen Square Institute of Neurology London UK Molecular Genomics Core Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH Bethesda MD USA Nash Family Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York NY USA Ronald M. Loeb Center for Alzheimer’s Disease Icahn School of Medicine at Mount Sinai New York NY USA Department of Pathology Fishberg Department of Neuroscience Icahn School of Medicine at Mount Sinai New York NY USA Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai New York NY USA Estelle and Daniel Maggin Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA Department of Genetics Evolution and Environment UCL Genetics Institute University College London London UK Mole

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WTO must complete an ambitious fisheries subsidies agreement

npj Ocean Sustainability

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npj Ocean Sustainability 2024年第1期3卷 1-3页

作者： U. Rashid Sumaila Lubna Alam William W. L. Cheung Daniel Pauly Philippe Le Billon Patrizia R. Abdallah Denis Aheto Shehu L. Akintola Justin Alger Vania Andreoli Dirk Zeller Jessica J. Meeuwig Megan Bailey Colin Barnes Abdulrahman Ben-Hasan Cassandra M. Brooks Adriana R. Carvalho Andrés M. Cisneros-Montemayor Jessica Dempsey Sharina A. Halim Mazlin Mokhtar Nathalie Hilmi Matthew O. Ilori Jennifer Jacquet Selma T. Karuaihe James Leape Tara G. Martin Fiorenza Micheli Rosamond L. Naylor David Obura Maria L. D. Palomares Laura M. Pereira Abbie A. Rogers Ana M. M. Sequeira Temitope O. Sogbanmu Sebastian Villasante Institute for the Oceans and Fisheries University of British Columbia Vancouver Canada School of Public Policy and Global Affairs University of British Columbia Vancouver Canada Sea Around Us Institute for the Oceans and Fisheries University of British Columbia Vancouver Canada Department of Geography University of British Columbia Vancouver Canada Instituto de Ciências Econômicas Administrativas e Contábeis Universidade Federal do Rio Grande Rio Grande RS Brazil Department of Fisheries and Aquatic Sciences University of Cape Coast Cape Coast Ghana Fisheries Department Lagos State University Lagos Nigeria School of Social and Political Sciences University of Melbourne 606W John Medley Building Parkville VIC 3010 Australia Sea Around Us – Indian Ocean School of Biological Sciences University of Western Australia Crawley WA Australia Marine Futures Lab School of Biological Sciences University of Western Australia Crawley WA Australia Marine Affairs Program Dalhousie University Halifax NS B3H 4R2 Canada Centre for Environment Energy and Natural Resource Governance University of Cambridge Cambridge CB2 3QZ UK Marine Science Department College of Science Kuwait University Kuwait City Kuwait Department of Environmental Studies University of Colorado Boulder USA Institute of Arctic and Alpine Research University of Colorado Boulder USA Department of Ecology Federal University of Rio Grande do Norte Natal Brazil School of Resource and Environmental Management Simon Fraser University Burnaby Canada Institute for Environment and Development (LESTARI) Universiti Kebangsaan Malaysia (UKM) Bangi Malaysia UN SDSN Asia Sunway University Selangor Malaysia Department of Environmental Economics Centre Scientifique de Monaco Monaco City Monaco Department of Microbiology University of Lagos Akoka-Yaba Lagos Nigeria Department of Environmental Science and Policy Abess Center for Ecosystem Science and Policy University of Miami Coral Gables FL USA Depar

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Drivers of seedling establishment success in dryland restoration efforts (Jul, 10.1038/s41559-021-01510-3, 2021)

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NATURE ECOLOGY & EVOLUTION 2021年第9期5卷 1319-1319页

作者： Shackelford, Nancy Paterno, Gustavo B. Winkler, Daniel E. Erickson, Todd E. Leger, Elizabeth A. Svejcar, Lauren N. Breed, Martin F. Faist, Akasha M. Harrison, Peter A. Curran, Michael F. Guo, Qinfeng Kirmer, Anita Law, Darin J. Mganga, Kevin Z. Munson, Seth M. Porensky, Lauren M. Quiroga, R. Emiliano Torok, Peter Wainwright, Claire E. Abdullahi, Ali Bahm, Matt A. Ballenger, Elizabeth A. Barger, Nichole Baughman, Owen W. Becker, Carina Lucas-Borja, Manuel Esteban Boyd, Chad S. Burton, Carla M. Burton, Philip J. Calleja, Eman Carrick, Peter J. Caruana, Alex Clements, Charlie D. Davies, Kirk W. Deak, Balazs Drake, Jessica Dullau, Sandra Eldridge, Joshua Espeland, Erin Farrell, Hannah L. Fick, Stephen E. Garbowski, Magda de la Riva, Enrique G. Golos, Peter J. Grey, Penelope A. Heydenrych, Barry Holmes, Patricia M. James, Jeremy J. Jonas-Bratten, Jayne Kiss, Reka Kramer, Andrea T. Larson, Julie E. Lorite, Juan Mayence, C. Ellery Merino-Martin, Luis Miglecz, Tamas Milton, Suanne Jane Monaco, Thomas A. Montalvo, Arlee M. Navarro-Cano, Jose A. Paschke, Mark W. Peri, Pablo Luis Pokorny, Monica L. Rinella, Matthew J. Saayman, Nelmarie Schantz, Merilynn C. Parkhurst, Tina Seabloom, Eric W. Stuble, Katharine L. Uselman, Shauna M. Valko, Orsolya Veblen, Kari Wilson, Scott Wong, Megan Xu, Zhiwei Suding, Katharine L. School of Environmental Studies University of Victoria Victoria British Columbia Canada Ecology and Evolutionary Biology University of Colorado Boulder Boulder CO USA Institute of Arctic and Alpine Research University of Colorado Boulder Boulder CO USA Departamento de Ecologia Universidade Federal do Rio Grande do Norte Natal Brazil Department of Ecology and Ecosystem Management Restoration Ecology Research Group Technical University of Munich Freising Germany US Geological Survey Southwest Biological Science Center Moab UT USA School of Biological Sciences The University of Western Australia Crawley Western Australia Australia Kings Park Science Department of Biodiversity Conservation and Attractions Kings Park Western Australia Australia Department of Biology University of Nevada Reno Reno NV USA USDA Agricultural Research Service Eastern Oregon Agricultural Research Center Burns OR USA College of Science and Engineering Flinders University Bedford Park South Australia Australia Department of Animal and Range Sciences New Mexico State University Las Cruces NM USA School of Natural Sciences and ARC Training Centre for Forest Value University of Tasmania Hobart Tasmania Australia Program in Ecology University of Wyoming Laramie WY USA USDA FS – Southern Research Station Research Triangle Park NC USA Department of Nature Conservation and Landscape Planning Anhalt University of Applied Sciences Bernburg Germany School of Natural Resources and the Environment University of Arizona Tucson AZ USA Department of Agricultural Sciences South Eastern Kenya University Kitui Kenya US Geological Survey Southwest Biological Science Center Flagstaff AZ USA US Department of Agriculture – Agricultural Research Service Rangeland Resources and Systems Research Unit Fort Collins CO USA Instituto Nacional de Tecnología Agropecuaria Estación Experimental Agropecuaria Catamarca Catamarca Argentina Cátedra de Manejo de Pastizales Naturales Facultad de Cienci

Restoration of degraded drylands is urgently needed to mitigate climate change, reverse desertification and secure livelihoods for the two billion people who live in these areas. Bold global targets have been set for dryland restoration to restore millions of hectares of degraded land. These targets have been questioned as overly ambitious, but without a global evaluation of successes and failures it is impossible to gauge feasibility. Here we examine restoration seeding outcomes across 174 sites on six continents, encompassing 594,065 observations of 671 plant species. Our findings suggest reasons for optimism. Seeding had a positive impact on species presence: in almost a third of all treatments, 100% of species seeded were growing at first monitoring. However, dryland restoration is risky: 17% of projects failed, with no establishment of any seeded species, and consistent declines were found in seeded species as projects matured. Across projects, higher seeding rates and larger seed sizes resulted in a greater probability of recruitment, with further influences on species success including site aridity, taxonomic identity and species life form. Our findings suggest that investigations examining these predictive factors will yield more effective and informed restoration decision-making.

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Polygenic risk modeling for prediction of epithelial ovarian cancer risk (vol 30, pg 349, 2021)

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EUROPEAN JOURNAL OF HUMAN GENETICS 2022年第5期30卷 630-631页

作者： Dareng, Eileen O. Tyrer, Jonathan P. Barnes, Daniel R. Jones, Michelle R. Yang, Xin Aben, Katja K. H. Adank, Muriel A. Agata, Simona Andrulis, Irene L. Anton-Culver, Hoda Antonenkova, Natalia N. Aravantinos, Gerasimos Arun, Banu K. Augustinsson, Annelie Balmana, Judith Bandera, Elisa V. Barkardottir, Rosa B. Barrowdale, Daniel Beckmann, Matthias W. Beeghly-Fadiel, Alicia Benitez, Javier Bermisheva, Marina Bernardini, Marcus Q. Bjorge, Line Black, Amanda Bogdanova, Natalia V. Bonanni, Bernardo Borg, Ake Brenton, James D. Budzilowska, Agnieszka Butzow, Ralf Buys, Saundra S. Cai, Hui Caligo, Maria A. Campbell, Ian Cannioto, Rikki Cassingham, Hayley Chang-Claude, Jenny Chanock, Stephen J. Chen, Kexin Chiew, Yoke-Eng Chung, Wendy K. Claes, Kathleen B. M. Colonna, Sarah Cook, Linda S. Couch, Fergus J. Daly, Mary B. Dao, Fanny Davies, Eleanor de la Hoya, Miguel de Putter, Robin Dennis, Joe DePersia, Allison Devilee, Peter Diez, Orland Ding, Yuan Chun Doherty, Jennifer A. Domchek, Susan M. Dork, Thilo du Bois, Andreas Durst, Matthias Eccles, Diana M. Eliassen, Heather A. Engel, Christoph Evans, Gareth D. Fasching, Peter A. Flanagan, James M. Fortner, Renee T. Machackova, Eva Friedman, Eitan Ganz, Patricia A. Garber, Judy Gensini, Francesca Giles, Graham G. Glendon, Gord Godwin, Andrew K. Goodman, Marc T. Greene, Mark H. Gronwald, Jacek Hahnen, Eric Haiman, Christopher A. Hakansson, Niclas Hamann, Ute Hansen, Thomas V. O. Harris, Holly R. Hartman, Mikael Heitz, Florian Hildebrandt, Michelle A. T. Hogdall, Estrid Hogdall, Claus K. Hopper, John L. Huang, Ruea-Yea Huff, Chad Hulick, Peter J. Huntsman, David G. Imyanitov, Evgeny N. Isaacs, Claudine Jakubowska, Anna James, Paul A. Janavicius, Ramunas Jensen, Allan Johannsson, Oskar Th. John, Esther M. Jones, Michael E. Kang, Daehee Karlan, Beth Y. Karnezis, Anthony Kelemen, Linda E. Khusnutdinova, Elza Kiemeney, Lambertus A. Kim, Byoung-Gie Kjaer, Susanne K. Komenaka, Ian Kupryjanczyk, Jolanta Kurian, Allison W. Kwong, Ava Lambrechts, Diether Larson, Melissa C. Lazaro, Conxi L University of Cambridge Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Cambridge UK University of Cambridge Centre for Cancer Genetic Epidemiology Department of Oncology Cambridge UK Center for Bioinformatics and Functional Genomics Cedars-Sinai Medical Center Los Angeles CA USA Radboud University Medical Center Radboud Institute for Health Sciences Nijmegen The Netherlands Netherlands Comprehensive Cancer Organisation Utrecht The Netherlands The Netherlands Cancer Institute—Antoni van Leeuwenhoek hospital Family Cancer Clinic Amsterdam The Netherlands Veneto Institute of Oncology IOV—IRCCS Immunology and Molecular Oncology Unit Padua Italy Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital Fred A. Litwin Center for Cancer Genetics Toronto ON Canada University of Toronto Department of Molecular Genetics Toronto ON Canada University of California Irvine Department of Epidemiology Genetic Epidemiology Research Institute Irvine CA USA N.N. Alexandrov Research Institute of Oncology and Medical Radiology Minsk Belarus ‘Agii Anargiri’ Cancer Hospital Athens Greece University of Texas MD Anderson Cancer Center Department of Breast Medical Oncology Houston TX USA Lund University Department of Cancer Epidemiology Clinical Sciences Lund Sweden Vall d’Hebron Institute of Oncology Hereditary cancer Genetics Group Barcelona Spain University Hospital of Vall d’Hebron Department of Medical Oncology Barcelona Spain Rutgers Cancer Institute of New Jersey Cancer Prevention and Control Program New Brunswick NJ USA Landspitali University Hospital Department of Pathology Reykjavik Iceland University of Iceland BMC (Biomedical Centre) Faculty of Medicine Reykjavik Iceland University Hospital Erlangen Friedrich-Alexander-University Erlangen-Nuremberg Department of Gynecology and Obstetrics Comprehensive Cancer Center ER-EMN Erlangen Germany Vanderbilt University School of Medicine Division of Epidemiology Department

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

关键词： Clinical genetics Genetic markers Risk factors Biomedicine general Human Genetics Bioinformatics Gene Expression Cytogenetics

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