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Drug Delivery: Composite Dissolving Microneedles for Coordinated Control of Antigen and Adjuvant Delivery Kinetics in Transcutaneous Vaccination (Adv. Funct. Mater. 2/2013)

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Advanced Functional Materials 2013年第2期23卷

作者： Peter C. DeMuth Wilfredo F. Garcia‐Beltran Michelle Lim Ai‐Ling Paula T. Hammond Darrell J. Irvine Department of Biological Engineering Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA Program in Health Sciences and Technology Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA Department of Materials Oxford University Oxford UK Department of Chemical Engineering Koch Institute for Integrative Cancer Research Institute for Soldier Nanotechnologies Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA Department of Materials Science and Engineering Department of Biological Engineering Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA Ragon Institute of MIT MGH and Harvard Boston MA 02139 USA Howard Hughes Medical Institute 4000 Jones Bridge Rd. Chevy Chase MD 20815 USA

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Machine Learning for Improved Current Density Reconstruction from 2D Vector Magnetic Images

arXiv

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arXiv 2024年

作者： Reed, Niko R. Bhutto, Danyal Turner, Matthew J. Daly, Declan M. Oliver, Sean M. Tang, Jiashen Olsson, Kevin S. Langellier, Nicholas Ku, Mark J.H. Rosen, Matthew S. Walsworth, Ronald L. Department of Physics University of Maryland College ParkMD United States Quantum Technology Center University of Maryland College ParkMD United States Joint Quantum Institute University of Maryland College ParkMD United States Department of Biomedical Engineering Boston University BostonMA United States A. A. Martinos Center for Biomedical Imaging Massachusetts General Hospital CharlestownMA United States Department of Electrical and Computer Engineering University of Maryland College ParkMD United States The MITRE Corporation McLeanVA22102 United States Intelligence Community Postdoctoral Research Fellowship Program University of Maryland College ParkMD20742 United States Department of Physics Harvard University CambridgeMA United States Department of Materials Science and Engineering University of Delaware NewarkDE19716 United States Department of Physics and Astronomy University of Delaware NewarkDE19716 United States Harvard Medical School 25 Shattuck St. BostonMA United States

The reconstruction of electrical current densities from magnetic field measurements is an important technique with applications in materials science, circuit design, quality control, plasma physics, and biology. Analytic reconstruction methods exist for planar currents, but break down in the presence of high spatial frequency noise or large standoff distance, restricting the types of systems that can be studied. Here, we demonstrate the use of a deep convolutional neural network for current density reconstruction from two-dimensional (2D) images of vector magnetic fields acquired by a quantum diamond microscope (QDM). Trained network performance significantly exceeds analytic reconstruction for data with high noise or large standoff distances. This machine learning technique can perform quality inversions on lower SNR data, significantly reducing the data collection time and permitting reconstructions of weaker and three-dimensional current sources. © 2024, CC BY.

关键词： Magnetic fields

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Author Correction: programmable RNA targeting with the single-protein CRISPR effector Cas7-11

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Nature 2022年第7923期608卷 E30页

作者： Ahsen Özcan Rohan Krajeski Eleonora Ioannidi Brennan Lee Apolonia Gardner Kira S Makarova Eugene V Koonin Omar O Abudayyeh Jonathan S Gootenberg McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology Cambridge MA USA. ETH Zurich Zurich Switzerland. Harvard University Harvard Medical School Virology Program Boston MA USA. National Center for Biotechnology Information National Library of Medicine National Institutes of Health Bethesda MD USA. McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology Cambridge MA USA. omarabu@mit.edu. McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology Cambridge MA USA. jgoot@mit.edu.

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Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

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Nature medicine 2024年第1期30卷 307页

作者： Nicole L Welch Meilin Zhu Catherine Hua Juliane Weller Marzieh Ezzaty Mirhashemi Tien G Nguyen Sreekar Mantena Matthew R Bauer Bennett M Shaw Cheri M Ackerman Sri Gowtham Thakku Megan W Tse Jared Kehe Marie-Martine Uwera Jacqueline S Eversley Derek A Bielwaski Graham McGrath Joseph Braidt Jeremy Johnson Felecia Cerrato Gage K Moreno Lydia A Krasilnikova Brittany A Petros Gabrielle L Gionet Ewa King Richard C Huard Samantha K Jalbert Michael L Cleary Nicholas A Fitzgerald Stacey B Gabriel Glen R Gallagher Sandra C Smole Lawrence C Madoff Catherine M Brown Matthew W Keller Malania M Wilson Marie K Kirby John R Barnes Daniel J Park Katherine J Siddle Christian T Happi Deborah T Hung Michael Springer Bronwyn L MacInnis Jacob E Lemieux Eric Rosenberg John A Branda Paul C Blainey Pardis C Sabeti Cameron Myhrvold Broad Institute of MIT and Harvard Cambridge MA USA. nicole_welch@g.harvard.edu. Harvard Program in Virology Division of Medical Sciences Harvard Medical School Boston MA USA. nicole_welch@g.harvard.edu. Broad Institute of MIT and Harvard Cambridge MA USA. Department of Biological Engineering Massachusetts Institute of Technology Cambridge MA USA. Division of Infectious Diseases Department of Medicine Massachusetts General Hospital Boston MA USA. Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK. Harvard Program in Biological and Biomedical Sciences Harvard Medical School Boston MA USA. Division of Health Sciences and Technology Harvard Medical School and Massachusetts Institute of Technology Cambridge MA USA. Department of Organismic and Evolutionary Biology Harvard University Cambridge MA USA. Harvard/Massachusetts Institute of Technology MD-PhD Program Harvard Medical School Boston MA USA. Department of Systems Biology Harvard Medical School Boston MA USA. State Health Laboratories Rhode Island Department of Health Providence RI USA. Massachusetts Department of Public Health Boston MA USA. Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention Atlanta GA USA. African Centre of Excellence for Genomics of Infectious Diseases Redeemer's University Ede Nigeria. Department of Biological Sciences College of Natural Sciences Redeemer's University Ede Nigeria. Molecular Biology Department and Center for Computational and Integrative Biology Massachusetts General Hospital Boston MA USA. Department of Immunology and Infectious Disease Harvard T.H. Chan School of Public Health Harvard University Boston MA USA. Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology Cambridge MA USA. Broad Institute of MIT and Harvard Cambridge MA USA. pardis

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Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study (vol 113, pg 1490, 2021)

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AMERICAN JOURNAL OF CLINICAL NUTRITION 2021年第6期113卷 1715-1715页

作者： Tsilidis, K. K. Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom Section of Nutrition and Metabolism International Agency for Research on Cancer Lyon France Department of Population Health Sciences Bristol Medical School University of Bristol Bristol United Kingdom Medical Research Council Integrative Epidemiology Unit Department of Population Health Sciences Bristol Medical School University of Bristol Bristol United Kingdom University Hospitals Bristol National Health Service Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre University of Bristol Bristol United Kingdom Medical Research Council Biostatistics Unit School of Clinical Medicine University of Cambridge Cambridge United Kingdom Department of Preventive Medicine and Community Health The University of Texas Medical Branch Galveston TX USA Nuffield Department of Population Health University of Oxford Oxford United Kingdom Division of Human Nutrition and Health Wageningen University & Research Wageningen Netherlands Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Bethesda MD USA Division of Clinical Epidemiology and Aging Research German Cancer Research Center (DKFZ) Heidelberg Germany Medical Genetics Service University Hospital Center (CHU) Nantes Nantes France Leeds Institute of Cancer and Pathology University of Leeds Leeds United Kingdom Huntsman Cancer Institute University of Utah Salt Lake City UT USA Department of Population Health Sciences University of Utah Salt Lake City UT USA Division of Preventive Oncology German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg Germany German Cancer Consortium (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany Institute for Health Research Kaiser Permanente Colorado Denver CO USA

Background The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Methods Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (OR SD ): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (OR SD : 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (OR SD : 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, c

关键词： Mendelian randomization genes nutrition supplements colorectal cancer

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Towards control of cellular decision-making networks in the epithelial-To-mesenchymal transition

arXiv

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arXiv 2018年

作者： Zanudo, Jorge Gomez Tejeda Guinn, M. Tyler Farquhar, Kevin Szenk, Mariola Steinway, Steven N. Balazsi, Gabor Albert, Reka Department of Physics Pennsylvania State University University ParkPA16802 United States Department of Medical Oncology Dana-Farber Cancer Center BostonMA02215 United States Cancer Program Eli and Edythe L. Broad Institute of Harvard and Massachusetts Institute of Technology CambridgeMA02142 United States Biomedical Engineering Department Stony Brook University Stony BrookNY11794 United States Laufer Center for Physical and Quantitative Biology Stony Brook University Stony BrookNY11794 United States Stony Brook Medical Scientist Training Program 101 Nicolls Road Stony BrookNY11794 United States Department of Medicine Johns Hopkins University School of Medicine BaltimoreMD21287 United States Department of Biology Pennsylvania State University University ParkPA16802 United States

We present the epithelial-To-mesenchymal transition (EMT) from two perspectives: experimental/technological and theoretical. We review the state of the current understanding of the regulatory networks that underlie EMT in three physiological contexts: embryonic development, wound healing, and metastasis. We describe the existing experimental systems and manipulations used to better understand the molecular participants and factors that influence EMT and metastasis. We review the mathematical models of the regulatory networks involved in EMT, with a particular emphasis on the network motifs (such as coupled feedback loops) that can generate intermediate hybrid states between the epithelial and mesenchymal states. Ultimately, the understanding gained about these networks should be translated into methods to control phenotypic outcomes, especially in the context of cancer therapeutic strategies. We present emerging theories of how to drive the dynamics of a network toward a desired dynamical attractor (e.g. an epithelial cell state) and emerging synthetic biology technologies to monitor and control the state of cells. Copyright © 2018, The Authors. All rights reserved.

关键词： Pathology

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Sensing the local magnetic environment through optically active defects in a layered magnetic semiconductor

arXiv

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arXiv 2022年

作者： Klein, Julian Song, Zhigang Pingault, Benjamin Dirnberger, Florian Chi, Hang Curtis, Jonathan B. Dana, Rami Bushati, Rezlind Quan, Jiamin Dekanovsky, Lukas Sofer, Zdenek Alù, Andrea Menon, Vinod M. Moodera, Jagadeesh S. Lončar, Marko Narang, Prineha Ross, Frances M. Department of Materials Science and Engineering Massachusetts Institute of Technology CambridgeMA02139 United States John A. Paulson School of Engineering and Applied Sciences Harvard University CambridgeMA United States College of Letters and Sciences UCLA Los AngelesCA90095 United States QuTech Delft University of Technology Delft2600 GA Netherlands Department of Physics City College of New York New YorkNY10031 United States Francis Bitter Magnet Laboratory Plasma Science and Fusion Center Massachusetts Institute of Technology CambridgeMA02139 United States U.S. Army CCDC Army Research Laboratory AdelphiMD20783 United States Department of Physics The Graduate Center City University of New York New YorkNY10016 United States Department of Electrical and Computer Engineering The University of Texas at Austin AustinTX78712 United States Photonics Initiative CUNY Advanced Science Research Center New YorkNY10031 United States Department of Electrical Engineering City College of the City University of New York New YorkNY10031 United States Physics Program Graduate Center City University of New York New YorkNY10026 United States Department of Inorganic Chemistry University of Chemistry and Technology Prague Technická 5 Prague 6166 28 Czech Republic Department of Physics Massachusetts Institute of Technology CambridgeMA02139 United States

Atomic-level defects in van der Waals (vdW) materials are essential building blocks for quantum technologies and quantum sensing applications. The layered magnetic semiconductor CrSBr is an outstanding candidate for exploring optically active defects owing to a direct gap in addition to a rich magnetic phase diagram including a recently hypothesized defect-induced magnetic order at low temperature. Here, we show optically active defects in CrSBr that are probes of the local magnetic environment. We observe spectrally narrow (1 meV) defect emission in CrSBr that is correlated with both the bulk magnetic order and an additional low temperature defect-induced magnetic order. We elucidate the origin of this magnetic order in the context of local and non-local exchange coupling effects. Our work establishes vdW magnets like CrSBr as an exceptional platform to optically study defects that are correlated with the magnetic lattice. We anticipate that controlled defect creation allows for tailor-made complex magnetic textures and phases with the unique ingredient of direct optical access. Copyright © 2022, The Authors. All rights reserved.

关键词： Magnetic semiconductors

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T-ICAHT: grading and prognostic impact of thrombocytopenia after CAR T-cell therapy

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Blood 2025年 blood2025028833页

作者： Rejeski, Kai Sanz, Jaime Fei, Teng Nair, Monica S. Hashmi, Hamza Avigdor, Abraham Beyar-Katz, Ofrat Bücklein, Veit L. Curran, Kevin J. Einarsdottir, Sigrun Esensten, Jonathan H. Glaubach, Netta Golan-Accav, Noa Gomez-Llobell, Marina Halamis, Iris Itzhaki, Orit Locke, Frederick L. Mailankody, Sham Marcus, Ronit Maus, Marcela V. Palomba, M. Lia Park, Jae H. Pasquini, Marcelo Raj, Sandeep Rajeeve, Sridevi Salles, Gilles Scordo, Michael Shah, Gunjan L. Shimoni, Avichai Subklewe, Marion Tix, Tobias Usmani, Saad Z. Valid, Ori Valtis, Yannis K. Zuckerman, Tsila Shah, Nirali N. Perales, Miguel-Angel Shouval, Roni Adult Bone Marrow Transplant Service Division of Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY United States Cellular Therapy Service Division of Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY United States Department of Medicine III Ludwig Maximilian University Hospital Ludwig Maximilian University Munich Munich Germany Departament de Medicina Universitat de Valencia Valencia Spain Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY United States Pediatric Oncology Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD United States Myeloma Service Division of Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY United States Division of Hematology and Bone Marrow Transplantation Chaim Sheba Medical Center Faculty of Medicine Tel Aviv University Tel Aviv Israel Department of Hematology and Bone Marrow Transplantation Rambam Health Care Campus Haifa Israel The Ruth and Bruce Rappaport Faculty of Medicine Haifa Technion Israel Department of Pediatrics Memorial Sloan Kettering Cancer Center New York NY United States Advanced Biotherapy Center Sheba Medical Center Ramat Gan Israel Bioinformatics and Big Data Team (Insight) Digital Information Technology Division Rambam Healthcare Campus Haifa Israel Ella Lemelbaum Institute for Immuno-Oncology Sheba Medical Center Ramat Gan Israel Department of Blood and Marrow Transplant and Cellular Immunotherapy Moffitt Cancer Center Tampa FL United States Cellular Immunotherapy Program Cancer Center Massachusetts General Hospital and Harvard Medical School Boston MA United States Lymphoma Service Division of Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY United States Department of Medicine Weill Cornell Medical College New York NY United States Medical College of Wisconsin Milwaukee WI United States

Immune effector cell–associated hematotoxicity (ICAHT) was recently introduced as a distinct toxicity category of chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. Although a grading system based solely on neutrophil counts was proposed (hereafter termed N-ICAHT), the prevalence and prognostic impact of thrombocytopenia remain poorly defined. In this multicenter observational study, we systematically examined patterns of thrombocytopenia in 744 patients treated with commercial CD19 CAR-T for B-cell non-Hodgkin lymphoma (B-NHL). We developed a grading system termed T-ICAHT, with thresholds that closely aligned with N-ICAHT, based on depth, duration, and timing of thrombocytopenia. In the core NHL data set, 43% of patients developed any-grade early T-ICAHT (days 0-30), with 23% developing severe (grade ≥3) manifestations. Late T-ICAHT (days 31-100) was observed in 42% (grade ≥3, 13%). Although T-ICAHT and N-ICAHT gradings showed some correlation, considerable discordance was noted. On multivariate analysis, bridging therapy, poor performance status, and high HEMATOTOX scores were associated with increased risk of severe early T-ICAHT. Patients with higher T-ICAHT grades showed increased platelet and red blood cell transfusion burden and more bleeding events. T-ICAHT grades were inversely associated with overall survival (OS), with landmarked 2-year estimates ranging from 67% (grade 0) to 48% (grade 1-2) and 35% (grade ≥3). In multivariable Cox regression analysis, the independent prognostic capacity of T-ICAHT for OS was confirmed. Finally, we validated T-ICAHT's clinical and prognostic utility in 3 external cohorts spanning an additional 599 pediatric and adult patients (NHL, multiple myeloma, and B-cell acute lymphoblastic leukemia), confirming its broad applicability. These findings support integrating T-ICAHT into the ICAHT framework to standardize thrombocytopenia grading in CAR-T recipients. © 2025 American Society of Hematology

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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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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

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NATURE GENETICS 2018年第12期50卷 1755-1755页

作者： Evangelou, Evangelos Warren, Helen R. Mosen-Ansorena, David Mifsud, Borbala Pazoki, Raha Gao, He Ntritsos, Georgios Dimou, Niki Cabrera, Claudia P. Karaman, Ibrahim Fu Liang Ng Evangelou, Marina Witkowska, Katarzyna Tzanis, Evan Hellwege, Jacklyn N. Giri, Ayush Edwards, Digna R. Velez Sun, Yan V. Cho, Kelly Gaziano, J. Michael Wilson, Peter W. F. Tsao, Philip S. Kovesdy, Csaba P. Esko, Tonu Magi, Reedik Milani, Lili Almgren, Peter Boutin, Thibaud Debette, Stephanie Ding, Jun Giulianini, Franco Holliday, Elizabeth G. Jackson, Anne U. Li-Gao, Ruifang Lin, Wei-Yu Luan, Jian'an Mangino, Massimo Oldmeadow, Christopher Prins, Bram Peter Qian, Yong Sargurupremraj, Muralidharan Shah, Nabi Surendran, Praveen Theriault, Sebastien Verweij, Niek Willems, Sara M. Zhao, Jing-Hua Amouyel, Philippe Connell, John de Mutsert, Renee Doney, Alex S. F. Farrall, Martin Menni, Cristina Morris, Andrew D. Noordam, Raymond Pare, Guillaume Poulter, Neil R. Shields, Denis C. Stanton, Alice Thom, Simon Abecasis, Goncalo Amin, Najaf Arking, Dan E. Ayers, Kristin L. Barbieri, Caterina M. Batini, Chiara Bis, Joshua C. Blake, Tineka Bochud, Murielle Boehnke, Michael Boerwinkle, Eric Boomsma, Dorret I. Bottinger, Erwin P. Braund, Peter S. Brumat, Marco Campbell, Archie Campbell, Harry Chakravarti, Aravinda Chambers, John C. Chauhan, Ganesh Ciullo, Marina Cocca, Massimiliano Collins, Francis Cordell, Heather J. Davies, Gail de Borst, Martin H. de Geus, Eco J. Deary, Ian J. Deelen, Joris Del Greco, Fabiola M. Demirkale, Cumhur Yusuf Dorr, Marcus Ehret, Georg B. Elosua, Roberto Enroth, Stefan Erzurumluoglu, A. Mesut Ferreira, Teresa Franberg, Mattias Franco, Oscar H. Gandin, Ilaria Gasparini, Paolo Giedraitis, Vilmantas Gieger, Christian Girotto, Giorgia Goel, Anuj Gow, Alan J. Gudnason, Vilmundur Guo, Xiuqing Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Harris, Sarah E. Hartman, Catharina A. Havulinna, Aki S. Hicks, Andrew A. Hofer, Edith Hofman, Albert Hottenga, Jouke-Jan Huffman, Jennifer E. Hwang, Shih-Jen Ingelsson, Erik James, Alan Jansen Department of Epidemiology and Biostatistics Imperial College London London UK. Department of Hygiene and Epidemiology University of Ioannina Medical School Ioannina Greece. William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK. National Institute for Health Research Barts Cardiovascular Biomedical Research Center Queen Mary University of London London UK. MRC-PHE Centre for Environment and Health Imperial College London London UK. Department of Mathematics Imperial College London London UK. Division of Epidemiology Department of Medicine Institute for Medicine and Public Health Vanderbilt Genetics Institute Vanderbilt University Medical Center Tennessee Valley Healthcare System (626)/Vanderbilt University Nashville TN USA. Vanderbilt Genetics Institute Vanderbilt Epidemiology Center Department of Obstetrics and Gynecology Vanderbilt University Medical Center Tennessee Valley Health Systems VA Nashville TN USA. Department of Epidemiology Emory University Rollins School of Public Health Atlanta GA USA. Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) VA Boston Healthcare System Boston MA USA. Division of Aging Department of Medicine Brigham and Women's Hospital Department of Medicine Harvard Medical School Boston MA USA. Atlanta VAMC and Emory Clinical Cardiovascular Research Institute Atlanta GA USA. VA Palo Alto Health Care System Division of Cardiovascular Medicine Stanford University School of Medicine Stanford CA USA. Nephrology Section Memphis VA Medical Center and University of Tennessee Health Science Center Memphis TN USA. Estonian Genome Center University of Tartu Tartu Estonia. Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Department Clinical Sciences Malmö Lund University Malmö Sweden. MRC

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

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