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Association of vaccine-specific regulatory T cells with reduced antibody response to repeated influenza vaccination

European journal of immunology 2023年第12期53卷 e2350525页

作者： Pin-Hung Lin Po-Ju Hsiao Ching-Fu Pan Ming-Tsan Liu Jann-Tay Wang Chi Ching Fang-Yi Wu Yi-Hsuan Lin Yu-Chan Yang Le-Yin Hsu Hung-Chih Yang Un-In Wu Graduate Institute of Microbiology College of Medicine National Taiwan University Taipei Taiwan. Department of Medical Research National Taiwan University Hospital Taipei Taiwan. Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan. Department of Internal Medicine College of Medicine National Taiwan University Taipei Taiwan. Center for Diagnostics and Vaccine Development Centers for Disease Control Taipei Taiwan. Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan. Graduate Program of Data Science National Taiwan University and Academia Sinica Taipei Taiwan. Department of Medicine National Taiwan University Cancer Center Taipei Taiwan.

Repeated annual influenza vaccinations have been associated with reduced vaccine-induced antibody responses. This prospective study aimed to explore the role of vaccine antigen-specific regulatory T (Treg) cells in antibody response to repeated annual influenza vaccination. We analyzed pre- and postvaccination hemagglutination inhibition (HI) titers, seroconversion rates, seroprotection rates, vaccine antigen hemagglutinin (HA)-specific Treg cells, and conventional T (Tconv) cells. We compared these parameters between vaccinees with or without vaccine-induced seroconversion. Our multivariate logistic regression revealed that prior vaccination was significantly associated with a decreased likelihood of achieving seroconversion for both H1N1(adjusted OR, 0.03; 95% CI, 0.01-0.13) and H3N2 (adjusted OR, 0.09; 95% CI, 0.03-0.30). Furthermore, individuals who received repeated vaccinations had significantly higher levels of pre-existing HA-specific Treg cells than those who did not. We also found that vaccine-induced fold-increases in HI titers and seroconversion were negatively correlated with pre-existing HA-specific Treg cells and positively correlated with the ratio of Tconv to Treg cells. Overall, our findings suggest that repeated annual influenza vaccination is associated with a lower vaccine-induced antibody response and a higher frequency of vaccine-specific Treg cells. However, a lower frequency of pre-existing Treg cells correlates with a higher postvaccination antibody response.

关键词： Influenza Regulatory T cells Repeated vaccination Seroconversion Seroprotection

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Incidence trends of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancers among males in Taiwan, 1980-2019: a population-based cancer registry study

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BMC cancer 2023年第1期23卷 213页

作者： Yu-Shiun Tsai Yong-Chen Chen Tzu-I Chen Yu-Kwang Lee Chun-Ju Chiang San-Lin You Wan-Lun Hsu Li-Jen Liao School of Medicine College of Medicine Fu-Jen Catholic University New Taipei City 242 Taiwan. Master Program of Big Data Analysis in Biomedicine College of Medicine Fu Jen Catholic University New Taipei City 242 Taiwan. Data Science Center College of Medicine Fu Jen Catholic University New Taipei City 242 Taiwan. Graduate Institute of Business Administration College of Management Fu Jen Catholic University New Taipei City 242062 Taiwan. Division of General Surgery Department of Surgery National Taiwan University Hospital Taipei 100 Taiwan. Graduate Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei 10055 Taiwan. Master Program of Big Data Analysis in Biomedicine College of Medicine Fu Jen Catholic University New Taipei City 242 Taiwan. 156521@mail.fju.edu.tw. Data Science Center College of Medicine Fu Jen Catholic University New Taipei City 242 Taiwan. 156521@mail.fju.edu.tw. Otolaryngology Head and Neck Surgery Far Eastern Memorial Hospital No. 21 Sec. 2 Nanya S. Rd. Banciao Dist. New Taipei City 220 Taiwan. liaolj@ntu.edu.tw. Head and Neck Cancer Surveillance & Research Group Far Eastern Memorial Hospital New Taipei Taiwan. liaolj@ntu.edu.tw. Department of Electrical Engineering Yuan Ze University Taoyuan Taiwan. liaolj@ntu.edu.tw.

In a country with a high prevalence of cigarette smoking, betel chewing, and alcohol drinking, cancers of the oral cavity, nasopharynx, and larynx were the fourth, twelfth and seventeenth leading causes of cancer death, respectively, for men in 2020. We analyzed patients with head and neck cancer from 1980 to 2019 from the Taiwan cancer Registration database and discussed the annual average percent change, average percent change, age period, and birth cohort. Obvious period effects and birth effects are seen in oral, oropharyngeal, and hypopharyngeal cancer; however, the most significant period effect was seen between 1990 and 2009, which mainly reflects the consumption of betel nuts per capita. In addition, the period effect lessens after 2010 in oral cancer and hypopharyngeal cancers, while oropharyngeal cancers remain an obvious period effect, which results from the rising prevalence of HPV. Due to the high prevalence rate of betel quid chewing and cigarette smoking in the 1990s, the government executed several acts. As a result, the age-adjusted incidence rates of oral, oropharyngeal, and hypopharyngeal cancers have flattened since 2010, which can be explained by the declining cigarette smoking rate. The strict policy indeed shows an obvious effect on the head and neck cancer incidence rates, and we expect to see a further decline in the future.

关键词： Age-period-cohort effect Head and neck cancers Incidence Secular trend

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The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)

arXiv

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arXiv 2023年

作者： Kazerooni, Anahita Fathi Khalili, Nastaran Liu, Xinyang Haldar, Debanjan Jiang, Zhifan Anwar, Syed Muhammed Albrecht, Jake Adewole, Maruf Anazodo, Udunna Anderson, Hannah Bagheri, Sina Baid, Ujjwal Bergquist, Timothy Borja, Austin J. Calabrese, Evan Chung, Verena Conte, Gian-Marco Dako, Farouk Eddy, James Ezhov, Ivan Familiar, Ariana Farahani, Keyvan Haldar, Shuvanjan Iglesias, Juan Eugenio Janas, Anastasia Johansen, Elaine Jones, Blaise V. Kofler, Florian LaBella, Dominic Lai, Hollie Anne Van Leemput, Koen Li, Hongwei Bran Maleki, Nazanin McAllister, Aaron S. Meier, Zeke Menze, Bjoern Moawad, Ahmed W. Nandolia, Khanak K. Pavaine, Julija Piraud, Marie Poussaint, Tina Prabhu, Sanjay P. Reitman, Zachary Rodriguez, Andres Rudie, Jeffrey D. Sanchez-Montano, Mariana Shaikh, Ibraheem Salman Shah, Lubdha M. Sheth, Nakul Shinohara, Russel Taki Tu, Wenxin Viswanathan, Karthik Wang, Chunhao Ware, Jeffrey B. Wiestler, Benedikt Wiggins, Walter Zapaishchykova, Anna Aboian, Mariam Bornhorst, Miriam de Blank, Peter Deutsch, Michelle Fouladi, Maryam Hoffman, Lindsey Kann, Benjamin Lazow, Margot Mikael, Leonie Nabavizadeh, Ali Packer, Roger Resnick, Adam Rood, Brian Vossough, Arastoo Bakas, Spyridon Linguraru, Marius George Children’s Hospital of Philadelphia PhiladelphiaPA United States Department of Neurosurgery University of Pennsylvania PhiladelphiaPA United States University of Pennsylvania PhiladelphiaPA United States Sheikh Zayed Institute for Pediatric Surgical Innovation Children’s National Hospital WashingtonDC United States Department of Neurosurgery Thomas Jefferson University Hospital PA United States Sage Bionetworks United States Lab Crestview Radiology Lagos Nigeria McGill University MontrealQC Canada Department of Radiology 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 Neurosurgery The University of Southern California CA United States Department of Radiology Duke University Medical Center United States Mayo Clinic MN United States Center for Global Health Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Informatics Technical University Munich Germany TranslaTUM - Central Institute for Translational Cancer Research Technical University of Munich Germany Cancer Imaging Program National Cancer Institute National Institutes of Health BethesdaMD United States Biomedical Engineering Rutgers University New BrunswickNJ United States Athinoula A Martinos Center for Biomedical Imaging Massachusetts General Hospital BostonMA United States Yale University New HavenCT United States PrecisionFDA U.S. Food and Drug Administration Silver SpringMD United States Cincinnati Children’s Hospital Medical Center United States Helmholtz AI Helmholtz Munich Germany Department of Radiation Oncology Duke University Medical Center United States Department of Radiology Children’s Health Orange County CA United States Department of Applied Mathematics and Computer Science Technical University of Denmark Denmark Department of Radiol

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors. © 2023, CC BY.

关键词： Tumors

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Genome-wide association study of long COVID

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Nature Genetics 2025年 1-16页

作者： Vilma Lammi Tomoko Nakanishi Samuel E. Jones Juha Karjalainen Martin Broberg Hele H. Haapaniemi Matti Pirinen Mari E. K. Niemi Mattia Cordioli Mark J. Daly Andrea Ganna Hanna M. Ollila J. Brent Richards Yukinori Okada Shea J. Andrews Beatriz Cortés Rafael de Cid Susana Iraola-Guzmán Natalia Blay Xavier Farré Heath E. O’Brien Thompson Hannah Patrick J. Short Ana Ochoa-Guzman Michelle Duran-Gomez Brian E. Fulton-Howard Masahiro Kanai Axel Schmidt Daniella Balla Julia Heggemann Sonja Schultz Pari Behzad Markus M. Nöthen Abigail Miller Kerstin U. Ludwig Ruth E. Mitchell George Davey Smith Nicholas J. Timpson Abdou Mousas Evangelos Evangelou Evangelia Ntzani Konstantinos K. Tsilidis Massimo Mangino Alicia Huerta-Chagoya Nasa Sinnott-Armstrong Elizabeth T. Cirulli Francisco Tanudjaja Efren Sandoval Nicole L. Washington Simon White Alexandre Bolze Kelly M. Schiabor Barrett Marc Vaudel Alex S. F. Kwong Amit K. Maiti Minttu M. Marttila Daniel C. Posner Alexis A. Rodriguez Chiara Batini Beatriz Guillen-Guio Olivia C. Leavy Anna L. Guyatt Catherine John Louise V. Wain Francesca Minnai Anna R. Dearman Benedict Hignell Meena Kumari C. A. Robert Warmerdam Lude H. Franke Celia B. Sequeros Søren Brunak David Westergaard Karina Banasik Thomas W. Winkler Iris M. Heid Daniel M. Jordan Ryan C. Thompson Alexander W. Charney Laura G. Sloofman Nicole W. Simons Noam D. Beckmann Raimonds Rešcenko Vita Rovite Peculis Raitis Monta Briviba Janis Klovinš Laura Ansone Lorenzo Miano Flora Peyvandi Francesco Malvestiti Nicola Montano Alessandra Bandera Francesco Bruno Arturo Blasi Jacqueline M. Lane Jakob M. Cherry Ryan K. Chung Laura Carvajal-Silva Kevin Aguilar-Valdés Leslie C. Cerpa Tamara V. Arévalo Eduardo Lamoza Alicia Colombo Ricardo A. Verdugo Erika Frangione Xu Xinyi Jennifer Taher Jordan Lerner-Ellis Lindsay Guare Shefali S. Verma Ekaterina Vergasova Michil Trofimov Layal Shaheen Nikolay Plotnikov Anna Kim Dmitrii Kharitonov Alexei Kamelin Alexander Rakitko Eirini Marouli Pasquale Striano Ummu Afeera Zainulabid Ashutosh Kumar Hajar Fa Institute for Molecular Medicine Finland (FIMM) Helsinki Institute of Life Science (HiLIFE) University of Helsinki Helsinki Finland Department of Human Genetics McGill University Montreal Quebec Canada Centre for Clinical Epidemiology Department of Medicine Lady Davis Institute Jewish General Hospital McGill University Montreal Quebec Canada Kyoto-McGill International Collaborative Program in Genomic Medicine Graduate School of Medicine Kyoto University Kyoto Japan Department of Genome Informatics Graduate School of Medicine the University of Tokyo Tokyo Japan Research Fellow Japan Society for the Promotion of Science Tokyo Japan Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA Stanley Center for Psychiatric Research Broad Institute of Harvard and MIT Cambridge MA USA Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA Department of Mathematics and Statistics University of Helsinki Helsinki Finland Department of Public Health University of Helsinki Helsinki Finland Broad Institute Cambridge MA USA Analytical and Translational Genetics Unit Massachusetts General Hospital Harvard Medical School Boston MA USA Center for Genomic Medicine Massachusetts General Hospital Boston MA USA Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Twin Research King’s College London London UK 5 Prime Sciences Inc Montreal Quebec Canada Department of Epidemiology Biostatistics and Occupational Health McGill University Montreal Quebec Canada Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan Laboratory of Statistical Immunology Immunology Frontier Research Center (WPI-IFReC) Osaka University Suita Japan Departmen

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association ofFOXP4with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4’s role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.

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The Brain Tumor Segmentation in Pediatrics (BraTS-PEDs) Challenge: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)

arXiv

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arXiv 2024年

作者： Kazerooni, Anahita Fathi Khalili, Nastaran Liu, Xinyang Gandhi, Deep Jiang, Zhifan Anwar, Syed Muhammed Albrecht, Jake Adewole, Maruf Anazodo, Udunna Anderson, Hannah Baid, Ujjwal Bergquist, Timothy Borja, Austin J. Calabrese, Evan Chung, Verena Conte, Gian-Marco Dako, Farouk Eddy, James Ezhov, Ivan Familiar, Ariana Farahani, Keyvan Franson, Andrea Gottipati, Anurag Haldar, Shuvanjan Iglesias, Juan Eugenio Janas, Anastasia Johansen, Elaine Jones, Blaise V. Khalili, Neda Kofler, Florian LaBella, Dominic Lai, Hollie Anne Van Leemput, Koen Li, Hongwei Bran Maleki, Nazanin McAllister, Aaron S. Meier, Zeke Menze, Bjoern Moawad, Ahmed W. Nandolia, Khanak K. Pavaine, Julija Piraud, Marie Poussaint, Tina Prabhu, Sanjay P. Reitman, Zachary Rudie, Jeffrey D. Sanchez-Montano, Mariana Shaikh, Ibraheem Salman Sheth, Nakul Tu, Wenxin Wang, Chunhao Ware, Jeffrey B. Wiestler, Benedikt Zapaishchykova, Anna Bornhorst, Miriam Deutsch, Michelle Fouladi, Maryam Lazow, Margot Mikael, Leonie Hummel, Trent Kann, Benjamin de Blank, Peter Hoffman, Lindsey Aboian, Mariam Nabavizadeh, Ali Packer, Roger Bakas, Spyridon Resnick, Adam Rood, Brian Vossough, Arastoo Linguraru, Marius George Children’s Hospital of Philadelphia PhiladelphiaPA United States Department of Neurosurgery University of Pennsylvania PhiladelphiaPA United States University of Pennsylvania PhiladelphiaPA United States Sheikh Zayed Institute for Pediatric Surgical Innovation Children’s National Hospital WashingtonDC United States Sage Bionetworks United States Lab Crestview Radiology Lagos Nigeria McGill University MontrealQC Canada Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Division of Computational Pathology Department of Pathology and Laboratory Medicine Indiana University School of Medicine IndianapolisIN United States Department of Neurosurgery The University of Southern California CA United States Department of Radiology Duke University Medical Center DurhamNC United States Mayo Clinic MN United States Center for Global Health Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Informatics Technical University Munich Germany TranslaTUM - Central Institute for Translational Cancer Research Technical University of Munich Germany Cancer Imaging Program National Cancer Institute National Institutes of Health BethesdaMD United States C. S. Mott Children’s Hospital University of Michigan MI United States Biomedical Engineering Rutgers University New BrunswickNJ United States Athinoula A Martinos Center for Biomedical Imaging Massachusetts General Hospital BostonMA United States Yale University New HavenCT United States PrecisionFDA U.S. Food and Drug Administration Silver SpringMD United States Cincinnati Children’s Hospital Medical Center OH United States Helmholtz AI Helmholtz Munich Germany Department of Radiation Oncology Duke University Medical Center DurhamNC United States Department of Radiology Children’s Health Orange County CA United States Department of Applied Mathematics and Computer Science Technical University of De

关键词： Deep learning

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115P Longterm prognostic utility of 70-gene signature by clinical and genomic risks, including Ultralow (gUL) risk patients (pts)

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ESMO Open 2023年第1期8卷 101339-101339页

作者： L. Sanz Gomez E. Zamora L. Joval C. Ortiz Velez M. Borrell Puy M.A. Arumi de Dios D.A. Gomez Puerto V. Navarro Garces M.A. Rezqallah Aron K.S. Vega Cano S. Escrivá-De-Romaní O. Mirallas I. Pimentel M. Cruellas Lapena G. Villacampa M. Oliveira C. Saura Manich P. Gomez Pardo V. Peg Cámara M. Bellet-Ezquerra Breast Cancer Unit-Dept. of Medical Oncology Vall d'Hebron Institute of Oncology Barcelona Spain Medical Oncology Vall d'Hebron University Hospital Barcelona Spain Oncology Data Science Group (ODysSey) VHIO Valle de Hebrón Instituto de Oncología Barcelona Spain Breast Cancer and Melanoma Dept. Vall d'Hebron University Hospital Barcelona Spain Dept. Medical Oncology Hospital Universitario Vall d'Hebron Barcelona Spain Oncology Department Universitat de Barcelona - Facultat de Medicina Barcelona Spain Medical Oncology Department Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center Barcelona Spain Oncology Data Science Group (ODysSey) Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center Barcelona Spain Oncología Médica Dept. Vall d'Hebron University Hospital Barcelona Spain Barcelona Vall d'Hebron University Hospital Barcelona Spain Medical Oncology-Breast Cancer Unit Vall d'Hebron University Hospital Barcelona Spain Medical Oncology Department Vall d'Hebron University Hospital Barcelona Spain Dept. Medical Oncology Vall d'Hebron University Hospital Barcelona Spain Statistics Department SOLTI - Grupo Espanol de Estudio Barcelona Spain Medical Oncology Dept. Vall d'Hebron University Hospital Barcelona Spain Head Breast Cancer Program Vall d'Hebron University Hospital Barcelona Spain Medical Oncology Dept. Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center Barcelona Spain Department of Pathology Vall d'Hebron University Hospital Barcelona Spain Oncology Dept. Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center Barcelona Spain

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RETRACTION: DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions (Retraction of Vol 528, Pg 517, 2015)

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NATURE 2018年第7725期562卷 150-150页

作者： Huang, Wendy Thomas, Benjamin Flynn, Ryan A. Gavzy, Samuel J. Wu, Lin Kim, Sangwon V. Hall, Jason A. Miraldi, Emily R. Ng, Charles P. Rigo, Frank Meadows, Sarah Montoya, Nina R. Herrera, Natalia G. Domingos, Ana I. Rastinejad, Fraydoon Myers, Richard M. Fuller-Pace, Frances V. Bonneau, Richard Chang, Howard Y. Acuto, Oreste Littman, Dan R. The Kimmel Center for Biology and Medicine of the Skirball Institute New York University School of Medicine New York New York 10016 USA. Sir William Dunn School of Pathology University of Oxford Oxford OX1 3RE UK. Center for Personal Dynamic Regulomes Stanford University Stanford California 94305 USA. Center for Genomics and Systems Biology Department of Biology New York University New York New York 10003 USA. Courant Institute of Mathematical Sciences Computer Science Department New York University New York New York 10012 USA. Simons Center for Data Analysis Simons Foundation New York New York 10010 USA. Isis Pharmaceuticals Carlsbad California 92010 USA. HudsonAlpha Institute for Biotechnology Huntsville Alabama 35806 USA. Instituto Gulbenkian de Ciencia Oeiras 2780-156 Portugal. Integrative Metabolism Program Sanford Burnham Prebys Medical Discovery Institute Orlando Florida 32827 USA. Division of Cancer Research University of Dundee Dundee DD1 9SY UK. The Kimmel Center for Biology and Medicine of the Skirball Institute New York University School of Medicine New York New York 10016 USA. Dan.Littman@med.nyu.edu. Howard Hughes Medical Institute New York University School of Medicine New York New York 10016 USA. Dan.Littman@med.nyu.edu.

Change History: This Article has been retracted; see accompanying Retraction. Corrected online 20 January: In this Article, author Frank Rigo was incorrectly listed with a middle initial; this has been corrected in th...

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Author Correction: Genetic drivers and cellular selection of female mosaic X chromosome loss

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Nature 2024年第8043期636卷 E7页

作者： Aoxing Liu Giulio Genovese Yajie Zhao Matti Pirinen Seyedeh M Zekavat Katherine A Kentistou Zhiyu Yang Kai Yu Caitlyn Vlasschaert Xiaoxi Liu Derek W Brown Georgi Hudjashov Bryan R Gorman Joe Dennis Weiyin Zhou Yukihide Momozawa Saiju Pyarajan Valdislav Tuzov Fanny-Dhelia Pajuste Mervi Aavikko Timo P Sipilä Awaisa Ghazal Wen-Yi Huang Neal D Freedman Lei Song Eugene J Gardner Vijay G Sankaran Aarno Palotie Hanna M Ollila Taru Tukiainen Stephen J Chanock Reedik Mägi Pradeep Natarajan Mark J Daly Alexander Bick Steven A McCarroll Chikashi Terao Po-Ru Loh Andrea Ganna John R B Perry Mitchell J Machiela Institute for Molecular Medicine Finland (FIMM) HiLIFE University of Helsinki Helsinki Finland. liuaoxin@***. Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA. liuaoxin@***. Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. liuaoxin@***. Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA. liuaoxin@***. Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA USA. liuaoxin@***. Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA. giulio@***. Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA USA. giulio@***. Department of Genetics Harvard Medical School Boston MA USA. giulio@***. MRC Epidemiology Unit Institute of Metabolic Science University of Cambridge Cambridge UK. Institute for Molecular Medicine Finland (FIMM) HiLIFE University of Helsinki Helsinki Finland. Department of Public Health University of Helsinki Helsinki Finland. Department of Mathematics and Statistics University of Helsinki Helsinki Finland. Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA. Cardiovascular Research Center Massachusetts General Hospital Boston MA USA. Department of Ophthalmology Massachusetts Eye and Ear Harvard Medical School Boston MA USA. Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA. Department of Medicine Queen's University Kingston Ontario Canada. Laboratory for Statistical and Translational Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan. Cancer Prevention Fellowship Program Division of Cancer Prevention National Cancer Institute Rockville MD USA. Estonian Genome Centre Institute of Genomics University of Tartu Tartu Estonia. Center for Data and Computational Sciences (C-DACS) VA Cooperative Studies Program VA Boston Health

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Shared genetic architecture of non-viral cirrhosis with several pleiotropic traits: A nested case-control study in the UK Biobank

Liver international communications

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Liver international communications 2024年第4期5卷 e70002页

作者： Jinyoung Byun Hyun-Seok Kim Younghun Han Aaron P Thrift Sabrina M Lin Xiangjun Xiao Hyeyeun Lim Goo Jun Stacia M Desantis Hashem B El-Serag Fasiha Kanwal Christopher I Amos Institute for Clinical and Translational Research Baylor College of Medicine Houston Texas USA. Section of Epidemiology and Population Sciences Department of Medicine Baylor College of Medicine Houston Texas USA. Section of Gastroenterology and Hepatology Baylor College of Medicine Houston Texas USA. Karsh Division of Gastroenterology and Hepatology Cedars-Sinai Medical Center Los Angeles California USA. Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine Houston Texas USA. Department of Molecular Biology Colgate University Hamilton New York USA. Department of Epidemiology Human Genetics & Environmental Sciences and Human Genetics Center School of Public Health University of Texas Health Science Center at Houston Houston Texas USA. Department of Biostatistics and Data Science The University of Texas Health Science Center at Houston School of Public Health Houston Texas USA. Clinical Epidemiology and Comparative Effectiveness Program Section of Health Services Research (IQuESt) Michael E. DeBakey Veterans Affairs Medical Center Houston Texas USA.

Background & Aims:Cirrhosis is a leading cause of liver-related mortality and a multifactorial disease. To date, the complex genetic architecture of non-viral cirrhosis has not been fully explored. Cross-trait genetic correlations can elucidate the common genetic etiology of genetically correlated phenotypes. This study aims to identify polygenic and pleiotropic traits associated with cirrhosis using the linkage disequilibrium score regression analysis. Methods:We conducted genome-wide association analysis of 9,622,842 imputed SNPs on 3,368 non-viral cirrhosis cases and 258,258 controls, and cross-trait analysis between non-viral cirrhosis and various polygenic and pleiotropic traits using the UK Biobank cohort study. We further performed sensitivity analyses by removing genomic regions of alcohol intake, smoking behaviors, and obesity. We observed multiple traits showing robust genetic correlations (rg) with non-viral cirrhosis. Results:We found strong genetic correlations between the genetic architectures of non-viral cirrhosis and clinical/physiologic factors, including BMI (rg=0.82), alanine aminotransferase (0.71), diabetes (0.70), number of cigarettes currently smoked daily (0.67), amount of alcohol drunk on a typical drinking day (0.60), insomnia (0.59), gout (0.57), depression (0.50), apoliprotein-A (-0.33), HDL cholesterol (-0.49). Exclusion of genomic regions associated with alcohol intake, smoking behaviors, and obesity demonstrated consistent directions and persistent associations in genetic patterns. The inheritability of cirrhosis on the observed scale showed 0.56%. Conclusions:This study provides a comprehensive assessment of the shared genetic architecture of non-viral cirrhosis predisposition and numerous polygenic and pleiotropic traits, most notably BMI, alanine aminotransferase, and diabetes. These findings provide new information on underlying comorbid conditions that can increase the non-viral cirrhosis risk.

关键词： Cirrhosis of the liver Cross-trait genetic analysis Genome-wide association study Polygenic inheritance UK Biobank

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PO002/#156 Efficacy and safety results from skyscraper-04: an open-label randomized phase 2 trial of tiragolumab plus atezolizumab for PD-L1-positive recurrent cervical cancer

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International Journal of Gynecological cancer 2023年 33卷 A1-A2页

作者： Ritu Salani Bradley Monk Yong-Man Kim Sharad Ghamande Shaundra Hall Domenica Lorusso Lisa Barraclough Lucy Gilbert Adrián Guzmán Ramírez Chien-Hsing Lu Dominique Berton Nicoletta Colombo Youyou Hu Venkatesh Krishnan Yuning Feng Nicole Kim Marcela Castro Yvonne Lin Mary Mccormack David Geffen School of Medicine UCLA Gynecology Los Angeles USA HonorHealth University of Arizona College of Medicine and Creighton University School of Medicine Division of Gynecologic Oncology Phoenix USA Gynecologic Cancer Center Asan Cancer Institute Asan Medical Center University of Ulsan Dept. of Obstetrics and Gynecology Seoul Republic of Korea Georgia Cancer Center Augusta University Gynecologic Oncology Augusta USA National Cervical Cancer Coalition Patient Advocacy Glendale USA Fondazione Policlinico Gemelli and Catholic University of the Sacred Heart Division of Gynecologic Oncology Rome Italy The Christie NHS Foundation Trust - Manchester UK McGill University Health Centre Department of Gynecologic Oncology Montreal Canada Instituto de Investigación en Ciencias Médicas (ICIMED) Oncology San José Costa Rica Taichung Veterans General Hospital Department of Obstetrics and Gynecology Taichung Taiwan Institut de Cancérologie de l’Ouest - Saint Herblain France University of Milan-Bicocca and Gynecologic Oncology Program European Institute of Oncology IRCCS Department of Medicine and Surgery Milan Italy F. Hoffmann-La Roche Ltd Data Science Basel Switzerland Genentech Oncology Biomarker Development South San Francisco USA Genentech Product Development Safety South San Francisco USA Genentech Product Development Oncology South San Francisco USA University College London Hospitals Department of Oncology London UK

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