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POS1474-HPR PERSONAL EXPERIENCES WITH DIAGNOSTIC DELAY AMONG AXIAL SPONDYLOARTHRITIS PATIENTS – A QUALITATIVE STUDY

Annals of the Rheumatic Diseases 2021年 80卷 1022-1022页

作者： C. Dubé K. Lapane K. Ferrucci A. Beccia S. Khan E. Yi J. Kay K.A. Kuhn A. Ogdie S.H. Liu University of Massachusetts Medical School Population and Quantitative Health Sciences Worcester United States of America University of Massachusetts Medical School Clinical and Population Health Research Program Graduate School of Biomedical Sciences Worcester United States of America Novartis Pharmaceuticals Corporation HE&OR and Medical Access East Hanover United States of America University of Massachusetts Medical School Division of Rheumatology Department of Medicine Worcester United States of America UMass Memorial Medical Center Rheumatology Center Worcester United States of America University of Colorado School of Medicine Department of Medicine Denver United States of America University of Pennsylvania Perelman School of Medicine Epidemiology and Biostatistics Center for Clinical Epidemiology and Biostatistics Philadelphia United States of America

Background: The estimated prevalence of axial Spondyloarthritis (axSpA) in the U.S. is 0.4 to 1.3 percent. Undiagnosed axSpA patients suffer from symptoms on average 7 to 10 years, which can also contribute to psychological suffering and healthcare burden due to the prolonged search for diagnosis and treatment. Objectives: To explore the experiences of diagnostic delay of axSpA patients as part of the SpondyloArthritis Screening and Early Detection (SpA-SED) Study. Methods: We conducted exploratory semi-structured patient focus groups. English-speaking participants ≥18 years of age with a rheumatologist-verified clinical diagnosis of axSpA were recruited from three rheumatology practices in Massachusetts, Colorado, and Pennsylvania. Six focus groups were conducted with 26 total participants (16 men, 10 women, age range 21-76 years). Discussions ranged from 1.33 to 2.13 hours. Verbatim transcripts were deidentified, cleaned and coded using NVivo qualitative software. A coding list was generated and summary themes were constructed. Results: Participants described meandering and frustrating journeys in search of a diagnosis. When doctors gave up, it was experienced by patients as profoundly negative. Intermittent axSpA symptoms confused some physicians and caused some patients to either delay seeking medical care (e.g., sporadic flare-up) or use dramatic language to convey the magnitude of the impact on their symptoms. Patients explained their experiences where physicians presumed that patients were trying to obtain narcotics or were “imagining/exaggerating” symptoms. Early symptom stories fell into five areas of importance for patients: pain, stiffness and lack of mobility, impact on sleep, impact on daily life, and changes with weather. Tenacity on the part of the patient and/or their family, patient research and confidence to challenge their physicians were important. Self-advocacy was challenging but necessary and particularly difficult when patients were sick. Dur

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Author Correction: An atlas of epithelial cell states and plasticity in lung adenocarcinoma

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Nature 2024年第8006期628卷 E1页

作者： Guangchun Han Ansam Sinjab Zahraa Rahal Anne M Lynch Warapen Treekitkarnmongkol Yuejiang Liu Alejandra G Serrano Jiping Feng Ke Liang Khaja Khan Wei Lu Sharia D Hernandez Yunhe Liu Xuanye Cao Enyu Dai Guangsheng Pei Jian Hu Camille Abaya Lorena I Gomez-Bolanos Fuduan Peng Minyue Chen Edwin R Parra Tina Cascone Boris Sepesi Seyed Javad Moghaddam Paul Scheet Marcelo V Negrao John V Heymach Mingyao Li Steven M Dubinett Christopher S Stevenson Avrum E Spira Junya Fujimoto Luisa M Solis Ignacio I Wistuba Jichao Chen Linghua Wang Humam Kadara Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Pulmonary Medicine The University of Texas MD Anderson Cancer Center Houston TX USA. Graduate Program in Developmental Biology Baylor College of Medicine Houston TX USA. The University of Texas Health Houston Graduate School of Biomedical Sciences Houston TX USA. Department of Biostatistics Epidemiology and Informatics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA. Department of Thoracic Head and Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Cardiovascular and Thoracic Surgery The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Epidemiology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Medicine The University of California Los Angeles Los Angeles CA USA. Lung Cancer Initiative at Johnson & Johnson Boston MA USA. Section of Computational Biomedicine School of Medicine Boston University Boston MA USA. Department of Pulmonary Medicine The University of Texas MD Anderson Cancer Center Houston TX USA. JChen16@***. The University of Texas Health Houston Graduate School of Biomedical Sciences Houston TX USA. JChen16@***. Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston TX USA. lwang22@***. The University of Texas Health Houston Graduate School of Biomedical Sciences Houston TX USA. lwang22@***. Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX USA. hkadara@***. The University of Texas Health Houston Graduate School of Biomedical Sciences Houston TX USA. hkadara@***.

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Interregional mobility in different age groups is associated with COVID-19 transmission in the Taipei metropolitan area, Taiwan

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Scientific reports 2023年第1期13卷 17285页

作者： Wei-Ming Jiang Tzai-Hung Wen Ying-Chi Huang Hung-Yi Chiou Wei J Chen Chao A Hsiung Huey-Kang Sytwu Hsiao-Hui Tsou Institute of Population Health Sciences National Health Research Institutes 35 Keyan Road Zhunan 350 Miaoli County Taiwan. Department of Geography National Taiwan University Taipei Taiwan. National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Zhunan Miaoli County Taiwan. School of Public Health College of Public Health Taipei Medical University Taipei Taiwan. Master's Program in Applied Epidemiology College of Public Health Taipei Medical University Taipei Taiwan. Center for Neuropsychiatric Research National Health Research Institutes Zhunan Miaoli County Taiwan. Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan. Institute of Population Health Sciences National Health Research Institutes 35 Keyan Road Zhunan 350 Miaoli County Taiwan. tsouhh@nhri.org.tw. Graduate Institute of Biostatistics College of Public Health China Medical University Taichung Taiwan. tsouhh@nhri.org.tw.

Before vaccines were introduced, mobility restriction was one of the primary control measures in the early stage of the coronavirus disease 2019 (COVID-19) pandemic. Because different age groups face disproportionate health risks, differences in their mobility changes affect the effectiveness of pandemic control measures. This study aimed to investigate the relationship between multiscale mobility patterns in different age groups and COVID-19 transmission before and after control measures implementation. Data on daily confirmed case numbers, anonymized mobile phone data, and 38 socioeconomic factors were used to construct negative binomial regression models of these relationships in the Taipei metropolitan area in May 2021. To avoid overfitting, the socioeconomic factor dimensions were reduced by principal component analysis. The results showed that inter-district mobility was a greater promoter of COVID-19 transmission than was intra-district mobility (coefficients: pre-alert, 0.52 and 0.43; post-alert, 0.41 and 0.36, respectively). Moreover, both the inter-district mobility of people aged 15-59 and ≥ 60 years were significantly related to the number of confirmed cases (coefficients: pre-alert, 0.82 and 1.05; post-alert, 0.48 and 0.66, respectively). The results can help agencies worldwide formulate public health responses to emerging infectious diseases.

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Human Gut Bacterial Metabolism Drives Th17 Activation and Colitis

SSRN

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SSRN 2020年

作者： Alexander, Margaret Ang, Qi Yan Nayak, Renuka R. Bustion, Annamarie E. Zhang, Bing Upadhyay, Vaibhav Pollard, Katherine S. Lynch, Susan V. Turnbaugh, Peter J. Department of Microbiology & Immunology University of California San Francisco CA94143 United States Rheumatology Division Department of Medicine University of California San FranciscoCA94158 United States Gladstone Institutes San FranciscoCA United States Pharmaceutical Sciences and Pharmacogenomics Graduate Program University of California San FranciscoCA United States Division of Gastroenterology and Hepatology University of California San FranciscoCA94158 United States Department of Medicine University of California San FranciscoCA94158 United States Chan Zuckerberg Biohub San FranciscoCA94158 United States Department of Epidemiology and Biostatistics University of California San Francisco San FranciscoCA United States

Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmune disease, yet the relevant human-associated bacteria for Th17-driven disease remain elusive. Here, we show the prevalent human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by upregulating interleukin (IL)-17 expression through a cell- and antigen-independent mechanism. E. lenta is enriched in inflammatory bowel disease patients and worsens colitis severity in a Rorc-dependent manner. We exploited natural E. lenta strain-level variation to identify a bacterial enzyme (Cardiac glycoside reductase 2, Cgr2) necessary and sufficient to induce IL-17a. The cgr2 gene is enriched in the gut microbiomes of autoimmune subjects and correlates with disease severity. Finally, we leveraged the sensitivity of Cgr2 to dietary arginine to prevent E. lenta-induced intestinal inflammation. Together, these results expand the mechanisms through which bacteria shape mucosal immunity and support a role of human gut bacterial metabolism in driving Th17-dependent autoimmune diseases. © 2020, The Authors. All rights reserved.

关键词： Chemical activation

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Mitigation of Chromosome Loss in Clinical CRISPR-Cas9-Engineered T Cells

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SSRN 2023年

作者： Tsuchida, Connor A. Brandes, Nadav Bueno, Raymund Trinidad, Marena Mazumder, Thomas Yu, Bingfei Hwang, Byungjin Chang, Christopher Liu, Jamin Sun, Yang Hopkins, Caitlin R. Parker, Kevin R. Qi, Yanyan Satpathy, Ansuman T. Stadtmauer, Edward A. Cate, Jamie H.D. Eyquem, Justin Fraietta, Joseph A. June, Carl H. Chang, Howard Y. Ye, Chun Jimmie Doudna, Jennifer A. University of California Berkeley - University of California San Francisco Graduate Program in Bioengineering University of California Berkeley BerkeleyCA United States Innovative Genomics Institute University of California Berkeley BerkeleyCA United States Division of Rheumatology Department of Medicine University of California San Francisco San FranciscoCA United States Center for Personal Dynamic Regulomes Stanford University StanfordCA United States Parker Institute for Cancer Immunotherapy Stanford University School of Medicine StanfordCA United States Biomedical Sciences Graduate Program University of California San Francisco San FranciscoCA United States Medical Scientist Training Program University of California San Francisco San FranciscoCA United States Department of Medicine University of California San Francisco San FranciscoCA United States Parker Institute for Cancer Immunotherapy San FranciscoCA United States Gladstone-UCSF Institute of Genomic Immunology San FranciscoCA United States Department of Biochemistry and Biophysics University of California San Francisco San FranciscoCA United States Abramson Cancer Center Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Parker Institute for Cancer Immunotherapy Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Center for Cellular Immunotherapies Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Microbiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Pathology Stanford University School of Medicine StanfordCA United States Division of Hematology-Oncology Department of Medicine Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department o

CRISPR-Cas9 genome editing has enabled advanced T cell therapies, but occasional loss of the targeted chromosome could be a safety concern. To investigate whether Cas9-induced chromosome loss is a universal phenomenon and evaluate its clinical significance, we conducted a systematic analysis in primary human T cells. Arrayed and pooled CRISPR screens revealed that partial or entire chromosome loss after Cas9-induced DNA cutting is a rare but generalized phenomenon, occurring also in pre-clinical chimeric antigen receptor T cells. T cells with chromosome loss persist for weeks in culture, implying potential interference with clinical use. A modified cell manufacturing process, employed in our first-in-human clinical trial of Cas9-engineered T cells, dramatically reduced chromosome loss while largely preserving genome editing efficacy. Expression of p53 correlated with the protection from chromosome loss observed with this protocol, suggesting both a mechanism and a strategy for T cell engineering that mitigates genotoxicity in the clinic. © 2023, The Authors. All rights reserved.

关键词： T-cells

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Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk

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European journal of human genetics : EJHG 2022年第5期30卷 630-631页

作者： Eileen O Dareng Jonathan P Tyrer Daniel R Barnes Michelle R Jones Xin Yang Katja K H Aben Muriel A Adank Simona Agata Irene L Andrulis Hoda Anton-Culver Natalia N Antonenkova Gerasimos Aravantinos Banu K Arun Annelie Augustinsson Judith Balmaña Elisa V Bandera Rosa B Barkardottir Daniel Barrowdale Matthias W Beckmann Alicia Beeghly-Fadiel Javier Benitez Marina Bermisheva Marcus Q Bernardini Line Bjorge Amanda Black Natalia V Bogdanova Bernardo Bonanni Ake Borg James D Brenton Agnieszka Budzilowska Ralf Butzow Saundra S Buys Hui Cai Maria A Caligo Ian Campbell Rikki Cannioto Hayley Cassingham Jenny Chang-Claude Stephen J Chanock Kexin Chen Yoke-Eng Chiew Wendy K Chung Kathleen B M Claes Sarah Colonna Linda S Cook Fergus J Couch Mary B Daly Fanny Dao Eleanor Davies Miguel de la Hoya Robin de Putter Joe Dennis Allison DePersia Peter Devilee Orland Diez Yuan Chun Ding Jennifer A Doherty Susan M Domchek Thilo Dörk Andreas du Bois Matthias Dürst Diana M Eccles Heather A Eliassen Christoph Engel Gareth D Evans Peter A Fasching James M Flanagan Renée T Fortner Eva Machackova Eitan Friedman Patricia A Ganz Judy Garber Francesca Gensini Graham G Giles Gord Glendon Andrew K Godwin Marc T Goodman Mark H Greene Jacek Gronwald Eric Hahnen Christopher A Haiman Niclas Håkansson Ute Hamann Thomas V O Hansen Holly R Harris Mikael Hartman Florian Heitz Michelle A T Hildebrandt Estrid Høgdall Claus K Høgdall John L Hopper Ruea-Yea Huang Chad Huff Peter J Hulick David G Huntsman Evgeny N Imyanitov Claudine Isaacs Anna Jakubowska Paul A James Ramunas Janavicius Allan Jensen Oskar Th Johannsson Esther M John Michael E Jones Daehee Kang Beth Y Karlan Anthony Karnezis Linda E Kelemen Elza Khusnutdinova Lambertus A Kiemeney Byoung-Gie Kim Susanne K Kjaer Ian Komenaka Jolanta Kupryjanczyk Allison W Kurian Ava Kwong Diether Lambrechts Melissa C Larson Conxi Lazaro Nhu D Le Goska Leslie Jenny Lester Fabienne Lesueur Douglas A Levine Lian Li Jingmei Li Jennifer T Loud Karen H Lu Jan Lubiński Phuong L Mai Siranoush Manoukian Jeffrey R Marks Ra 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 Epide

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Shared genetic architectures of educational attainment in East Asian and European populations

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Nature human behaviour 2024年第3期8卷 562-575页

作者： Tzu-Ting Chen Jaeyoung Kim Max Lam Yi-Fang Chuang Yen-Ling Chiu Shu-Chin Lin Sang-Hyuk Jung Beomsu Kim Soyeon Kim Chamlee Cho Injeong Shim Sanghyeon Park Yeeun Ahn Aysu Okbay Hyemin Jang Hee Jin Kim Sang Won Seo Woong-Yang Park Tian Ge Hailiang Huang Yen-Chen Anne Feng Yen-Feng Lin Woojae Myung Chia-Yen Chen Hong-Hee Won Center for Neuropsychiatric Research National Health Research Institutes Miaoli Taiwan. Department of Digital Health Samsung Advanced Institute for Health Sciences and Technology (SAIHST) Sungkyunkwan University Samsung Medical Center Seoul South Korea. Department of Neuropsychiatry Seoul National University Bundang Hospital Seongnam South Korea. Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA. Department of Medicine Harvard Medical School Boston MA USA. Human Genetics Genome Institute of Singapore Singapore Singapore. Division of Psychiatry Research the Zucker Hillside Hospital Northwell Health Glen Oaks NY USA. Research Division Institute of Mental Health Singapore Singapore Singapore. Institute of Public Health and International Health Program College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan. Graduate Institute of Medicine Yuan Ze University Taoyuan City Taiwan. Department of Medical Research Far Eastern Memorial Hospital New Taipei City Taiwan. Department of Biostatistics Epidemiology and Informatics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA. Stanley Center for Psychiatric Research the Broad Institute of MIT and Harvard Cambridge MA USA. Department of Economics School of Business and Economics Vrije Universiteit Amsterdam Amsterdam the Netherlands. Departments of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea. Alzheimer's Disease Convergence Research Center Samsung Medical Center Seoul South Korea. Samsung Genome Institute Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea. Psychiatric and Neurodevelopmental Genetics Unit Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston MA USA. Institute of Health Data Analytics and Statistics College of Public Health

Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.

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A structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes

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Cell Reports Medicine 2025年第5期6卷 102084-102084页

作者： Han, Xudong Zhang, Yichi Petrosky, Jillian N. Bald, Sarah Sherva, Richard M. Labadorf, Adam Cherry, Jonathan D. Chung, Jaeyoon Farrell, Kurt Abdolmohammadi, Bobak Durape, Shruti Martin, Brett M. Palmisano, Joseph N. Farrell, John J. Alvarez, Victor E. Huber, Bertrand R. Dwyer, Brigid Daneshvar, Daniel H. Jun, Gyungah R. Lunetta, Kathryn L. Goldstein, Lee E. Katz, Douglas I. Cantu, Robert C. Shenton, Martha E. Cummings, Jeffrey L. Reiman, Eric M. Stern, Robert A. Alosco, Michael L. Tripodis, Yorghos Farrer, Lindsay A. Stein, Thor D. Crary, John F. McKee, Ann C. Mez, Jesse Bioinformatics Graduate Program Boston University Boston MA United States Section of Biomedical Genetics Department of Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA United States Department of Neurology Boston University Chobanian & Avedisian School of Medicine Boston MA United States Boston University Alzheimer's Disease Research Center Boston University Chobanian & Avedisian School of Medicine Boston MA United States Boston VA Healthcare System Boston MA United States Boston University Chronic Traumatic Encephalopathy Center Boston University Boston MA United States Department of Pathology and Laboratory Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA United States Departments of Pathology Neuroscience and Artificial Intelligence & Human Health Neuropathology Brain Bank & Research CoRE Friedman Brain Institute Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai New York NY United States Biostatistics and Epidemiology Data Analytics Center Boston University School of Public Health Boston MA United States Bedford VA Healthcare System Bedford MA United States Braintree Rehabilitation Hospital Braintree MA United States Department of Physical Medicine and Rehabilitation Harvard Medical School Boston MA United States Department of Rehabilitation and Human Performance Brain Injury Research Center Icahn School of Medicine at Mount Sinai New York NY United States Department of Neurology Icahn School of Medicine at Mount Sinai New York NY United States Department of Biostatistics Boston University School of Public Health Boston MA United States Department of Ophthalmology Boston University Chobanian & Avedisian School of Medicine Boston MA United States Departments of Biomedical Electrical & Computer Engineering Boston University College of Engineering Boston MA United States Departments of Radiology and Psychiatry Boston University Chobanian & Avedisia

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. Genetic variation in the 17q21.31 region, containing microtubule-associated protein tau (MAPT), has been implicated in tauopathies but has not been investigated in CTE. The region includes a megabase-long inversion (H1/H2) and copy-number variations, including α, β, and γ segments, which can be characterized as nine segregating structural haplotypes. We leveraged array SNP data and a reference panel across the 17q21.31 region to impute structural haplotypes and test their association with CTE endophenotypes in 447 European ancestry brain donors with RHI exposure. The H1β1γ1 haplotype was significantly associated with dementia and semi-quantitative tau burden in multiple cortical and medial temporal regions commonly affected in CTE. H1β1γ1 differential expression analyses in dorsolateral frontal cortex implicated cis-acting genes and inflammatory pathways. Taken together, the H1β1γ1 haplotype may help explain CTE heterogeneity among those with similar RHI exposure. © 2025 The Authors

关键词： 17q21.31 chronic traumatic encephalopathy dementia differential gene expression immune system MAPT repetitive head impacts structural haplotypes tauopathy traumatic brain injury

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The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2

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Cell 2025年

作者： Pekar, Jonathan E. Lytras, Spyros Ghafari, Mahan Magee, Andrew F. Parker, Edyth Wang, Yu Ji, Xiang Havens, Jennifer L. Katzourakis, Aris Vasylyeva, Tetyana I. Suchard, Marc A. Hughes, Alice C. Hughes, Joseph Rambaut, Andrew Robertson, David L. Dellicour, Simon Worobey, Michael Wertheim, Joel O. Lemey, Philippe Institute of Ecology and Evolution University of Edinburgh Edinburgh United Kingdom Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla 92093 CA United States Department of Biomedical Informatics University of California San Diego La Jolla 92093 CA United States Department of Medicine University of California San Diego La Jolla 92093 CA United States Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan Medical Research Council University of Glasgow Centre for Virus Research Glasgow United Kingdom Department of Biology University of Oxford Oxford United Kingdom Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los Angeles 90095 CA United States Department of Immunology and Microbiology The Scripps Research Institute La Jolla 92037 CA United States Institute of Genomics and Global Health Redeemer's University Osun State Ede Nigeria Department of Computer Science and Engineering University of California San Diego La Jolla 92093 CA United States Department of Mathematics School of Science and Engineering Tulane University New Orleans LA United States Department of Population Health and Disease Prevention University of California Irvine Irvine 92617 CA United States Department of Biostatistics Fielding School of Public Health University of California Los Angeles Los Angeles 90095 CA United States Department of Computational Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles 90095 CA United States School of Biological Sciences University of Hong Kong Hong Kong Hong Kong China Biodiversity Green Development Foundation Beijing China Spatial Epidemiology Lab (SpELL) Université Libre de Bruxelles CP160/12 50 av. FD Roosevelt Bruxelles 1050 Belgium Department of Microbiology Immunology and Transplantation Rega Institute

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 led to increased sampling of sarbecoviruses circulating in horseshoe bats. Employing phylogenetic inference while accounting for recombination of bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed less than a decade prior to their emergence in humans. Phylogeographic analyses show bat sarbecoviruses traveled at rates approximating their horseshoe bat hosts and circulated in Asia for millennia. We find that the direct ancestors of SARS-CoV and SARS-CoV-2 are unlikely to have reached their respective sites of emergence via dispersal in the bat reservoir alone, supporting interactions with intermediate hosts through wildlife trade playing a role in zoonotic spillover. These results can guide future sampling efforts and demonstrate that viral genomic regions extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses. © 2025 The Authors

关键词： molecular epidemiology phylogeography sarbecoviruses virus evolution

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A call to action: the second Lancet Commission on adolescent health and wellbeing

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Lancet (London, England) 2025年第10493期405卷 1945-2022页

作者： Sarah Baird Shakira Choonara Peter S Azzopardi Prerna Banati Judith Bessant Olivia Biermann Anthony Capon Mariam Claeson Pamela Y Collins Nicole De Wet-Billings Surabhi Dogra Yanhui Dong Kate L Francis Luwam T Gebrekristos Allison K Groves Simon I Hay David Imbago-Jácome Aaron P Jenkins Caroline W Kabiru Elissa C Kennedy Luo Li Chunling Lu Jun Ma Terry McGovern Augustina Mensa-Kwao Sanyu A Mojola Jason M Nagata Adesola O Olumide Olayinka Omigbodun Molly O'Sullivan Audrey Prost Jennifer H Requejo Yusra R Shawar Jeremy Shiffman Avi Silverman Yi Song Sharlene Swartz Rita Tamambang Henrik Urdal Joseph L Ward George C Patton Susan M Sawyer Alex Ezeh Russell M Viner Department of Global Health Milken Institute School of Public Health George Washington University Washington DC USA. Electronic address: sbaird@email.gwu.edu. Johannesburg South Africa. Adolescent Health Murdoch Children's Research Institute Parkville VIC Australia Department of Paediatrics University of Melbourne Parkville VIC Australia Adolescent Health and Wellbeing Program The Kids Research Institute of Australia Perth WA Australia National Centre for Epidemiology and Population Health Australian National University Canberra ACT Australia. Department of Maternal Newborn Child & Adolescent Health & Ageing World Health Organization Geneva Switzerland. School of Global Urban and Social Studies RMIT University Melbourne VIC Australia. Department of Global Public Health Karolinska Institutet Stockholm Sweden. Monash Sustainable Development Institute Monash University Melbourne VIC Australia. Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA Department of Psychiatry & Behavioral Sciences Johns Hopkins University School of Medicine Baltimore MD USA. Academic Affairs University of the Witwatersrand Johannesburg South Africa. Emerging Professionals Network International Association for Adolescent Health Gautam Buddha Nagar India. Institute of Child and Adolescent Health School of Public Health Peking University Beijing China National Health Commission Key Laboratory of Reproductive Health Beijing China. Department of Paediatrics University of Melbourne Parkville VIC Australia. Department of Epidemiology & Biostatistics Drexel University Dornsife School of Public Health Philadelphia PA USA. Community Health and Prevention Drexel Dornsife School of Public Health Philadelphia PA USA. Institute for Health Metrics and Evaluation and Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA USA. Quito Ecuador. Pacific Planetary Health Hub Sydney Institute for Infectious Di

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