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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.Haffner Nichlas D.Socci Richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin Department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan Kettering Cancer Center New YorkNYUSA Department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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Frailty and Other Factors Associated With Early Outcomes in Middle-to Older Age Trauma Patients: A Prospective Cohort Study

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American Journal of Geriatric Psychiatry 2024年第2期32卷 244-255页

作者： Yeh, Tian-Shin Kang, Jiunn-Horng Littlejohns, Thomas J. Wu, Chia-Chieh Chen, Jin-Hua Piravej, Krisna Chiu, Wen-Ta Lam, Carlos Department of Physical Medicine and Rehabilitation School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Physical Medicine and Rehabilitation Wan Fang Hospital Taipei Medical University Taipei Taiwan Department of Epidemiology and Nutrition Harvard T. H. Chan School of Public Health Harvard University Boston MA United States Department of Physical Medicine and Rehabilitation National Taiwan University Hospital Taipei Taiwan Department of Physical Medicine and Rehabilitation College of Medicine National Taiwan University Taipei Taiwan Department of Physical Medicine and Rehabilitation Taipei Medical University Hospital Taipei Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei Taiwan Professional Master Program in Artificial Intelligence in Medicine College of Medicine Taipei Medical University Taipei Taiwan Nuffield Department of Population Health University of Oxford Oxford United Kingdom Emergency Department Wan Fang Hospital Taipei Medical University Taipei Taiwan Department of Emergency School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Data Science College of Management Taipei Medical University Taipei Taiwan Institutional Research Center Office of Data Science Taipei Medical University Taipei Taiwan Biostatistics Center Department of Medical Research Wan Fang Hospital Taipei Medical University Taipei Taiwan Department of Rehabilitation Medicine Faculty of Medicine Chulalongkorn University Bangkok Thailand Department of Chula Neuroscience Center King Chulalongkorn Memorial Hospital Bangkok Thailand Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei Taiwan AHMC Health System Alhambra CA United States

Objectives: To prospectively investigate associations of frailty and other predictor variables with functional recovery and health outcomes in middle-aged and older patients with trauma. Design: Single-center prospective cohort study. Setting: Emergency department of Wan Fang Hospital in Taiwan. Participants: Trauma patients aged 45 and older. Measurements: Frailty was assessed with the Clinical Frailty Scale (CFS). Injury mechanisms, pre-existing diseases, and fracture locations were recorded at baseline. The primary outcome was functional recovery assessed using the Barthel Index (BI). Secondary outcomes were new care needs, unscheduled return visits, and falls 3 months postinjury. Results: A total of 588 participants were included in the final analysis. For every one-point increase in the CFS, the multivariable-adjusted odds ratio (OR, 95% confidence interval [CI]) of failure to retain the preinjury BI was 1.34 (1.16–1.55);associations were consistent across levels of age and injury severities. Significant joint associations of frailty and age with poor functional recovery were observed. CFS was also associated with new care needs (OR for every one-point increase, 1.36, 95% CI, 1.17–1.58), unscheduled return visits (OR 1.26, 95% CI, 1.04–1.51), and falls (OR 1.23, 95% CI, 1.01–1.51). Other variables associated with failure to retain preinjury BI included road traffic accident and presence of hip fracture. Conclusion: Frailty was significantly associated with poor functional and health outcomes regardless of injury severity in middle-aged and older patients with trauma. Injury mechanisms and fracture locations were also significant predictors of functional recovery postinjury. © 2023 American Association for Geriatric Psychiatry

关键词： Clinical Frailty Scale Frailty functional recovery injury middle-to older age

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Impact of pandemic fatigue on the spread of COVID-19: A mathematical modelling study

arXiv

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arXiv 2021年

作者： Tang, Disheng Cao, Wei Bian, Jiang Liu, Tie-Yan Gao, Zhifeng Zheng, Shun Liu, Jue Interdisciplinary Graduate Program in Quantitative Biosciences Georgia Institute of Technology AtlantaGA United States School of Earth and Atmospheric Sciences Georgia Institute of Technology AtlantaGA United States Microsoft Research Asia Beijing China Department of Epidemiology and Biostatistics School of Public Health Peking University Beijing China

In late-2020, many countries around the world faced another surge in number of confirmed cases of COVID-19, including United Kingdom, Canada, Brazil, United States, etc., which resulted in a large nationwide and even worldwide wave. While there have been indications that precaution fatigue could be a key factor, no scientific evidence has been provided so far. We used a stochastic metapopulation model with a hierarchical structure and fitted the model to the positive cases in the US from the start of outbreak to the end of 2020. We incorporated non-pharmaceutical interventions (NPIs) into this model by assuming that the precaution strength grows with positive cases and studied two types of pandemic fatigue. We found that people in most states and in the whole US respond to the outbreak in a sublinear manner (with exponent k=0.5), while only three states (Massachusetts, New York and New Jersey) have linear reaction (k=1). Case fatigue (decline in people's vigilance to positive cases) is responsible for 58% of cases, while precaution fatigue (decay of maximal fraction of vigilant group) accounts for 26% cases. If there were no pandemic fatigue (no case fatigue and no precaution fatigue), total positive cases would have reduced by 68% on average. Our study shows that pandemic fatigue is the major cause of the worsening situation of COVID-19 in United States. Reduced vigilance is responsible for most positive cases, and higher mortality rate tends to push local people to react to the outbreak faster and maintain vigilant for longer time. © 2021, CC BY.

关键词： Stochastic systems

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Economic assessment of foot-and-mouth disease outbreaks in Brazil

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Q Open 2022年第2期2卷

作者： De Menezes, Taís Cristina Countryman, Amanda M Ferreira Filho, Joaquim Bento De Souza Ferreira, Fernando Graduate Program in Agricultural Economics Colorado State University Fort Collins 80523 CO United States Agricultural and Resource Economics Department Colorado State University Fort Collins 80523 CO United States Department of Economics Administration and Sociology Luiz de Queiroz College of Agriculture University of São Paulo Piracicaba 13403 Brazil Laboratory of Epidemiology and Biostatistics School of Veterinary Medicine and Animal Science University of São Paulo São Paulo 05508060 Brazil

Foot-and-mouth disease (FMD) outbreaks in cloven-hoofed animals cause substantial economic impacts because of animal depopulation, increased government spending on control, eradication and surveillance measures, and bans on international trade. This study employs a computable general equilibrium (CGE) modeling framework in tandem with results from an epidemiological model to evaluate the economic consequences of a hypothetical FMD outbreak in Brazil. FMD-induced productivity losses and restrictions on international trade of livestock and meat products are applied as exogenous shocks in the economic model. Results show increased bilateral trade of beef and pork, mainly in South America, North Africa, and Russia. Simulated welfare losses in Brazil range from $132 million to $271 million depending on the severity of trade restrictions imposed. This study expands the rich literature on animal health economics. Results highlight the importance of maintaining the health of Brazilian herds, especially when considering Brazil's position as one of the main meat suppliers in the international market. © 2022 The Author(s). Published by Oxford University in association with European Agricultural and Applied Economics Publications Foundation.

关键词： Animal health economics Brazil Foot-and-mouth disease International trade

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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries (vol 55, pg 89, 2023)

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NATURE GENETICS 2023年第3期55卷 519-520页

作者： Fernandez-Rozadilla, Ceres Timofeeva, Maria Chen, Zhishan Law, Philip Thomas, Minta Schmit, Stephanie Diez-Obrero, Virginia Hsu, Li Fernandez-Tajes, Juan Palles, Claire Sherwood, Kitty Briggs, Sarah Svinti, Victoria Donnelly, Kevin Farrington, Susan Blackmur, James Vaughan-Shaw, Peter Shu, Xiao-ou Long, Jirong Cai, Qiuyin Guo, Xingyi Lu, Yingchang Broderick, Peter Studd, James Huyghe, Jeroen Harrison, Tabitha Conti, David Dampier, Christopher Devall, Mathew Schumacher, Fredrick Melas, Marilena Rennert, Gad Obon-Santacana, Mireia Martin-Sanchez, Vicente Moratalla-Navarro, Ferran Oh, Jae Hwan Kim, Jeongseon Jee, Sun Ha Jung, Keum Ji Kweon, Sun-Seog Shin, Min-Ho Shin, Aesun Ahn, Yoon-Ok Kim, Dong-Hyun Oze, Isao Wen, Wanqing Matsuo, Keitaro Matsuda, Koichi Tanikawa, Chizu Ren, Zefang Gao, Yu-Tang Jia, Wei-Hua Hopper, John Jenkins, Mark Win, Aung Ko Pai, Rish Figueiredo, Jane Haile, Robert Gallinger, Steven Woods, Michael Newcomb, Polly Duggan, David Cheadle, Jeremy Kaplan, Richard Maughan, Timothy Kerr, Rachel Kerr, David Kirac, Iva Bohm, Jan Mecklin, Lukka-Pekka Jousilahti, Pekka Knekt, Paul Aaltonen, Lauri Rissanen, Harri Pukkala, Eero Eriksson, Johan Cajuso, Tatiana Hanninen, Ulrika Kondelin, Johanna Palin, Kimmo Tanskanen, Tomas Renkonen-Sinisalo, Laura Zanke, Brent Mannisto, Satu Albanes, Demetrius Weinstein, Stephanie Ruiz-Narvaez, Edward Palmer, Julie Buchanan, Daniel Platz, Elizabeth Visvanathan, Kala Ulrich, Cornelia Siegel, Erin Brezina, Stefanie Gsur, Andrea Campbell, Peter Chang-Claude, Jenny Hoffmeister, Michael Brenner, Hermann Slattery, Martha Potter, John Tsilidis, Konstantinos Schulze, Matthias Gunter, Marc Murphy, Neil Castells, Antoni Castellvi-Bel, Sergi Moreira, Leticia Arndt, Volker Shcherbina, Anna Stern, Mariana Pardamean, Bens Bishop, Timothy Giles, Graham Southey, Melissa Idos, Gregory McDonnell, Kevin Abu-Ful, Zomoroda Greenson, Joel Shulman, Katerina Lejbkowicz, Flavio Offit, Kenneth Su, Yu-Ru Steinfelder, Robert Keku, Temitope van Guelpen, Bethany Hudson, Thomas Hampel, Heather Pearlman, Edinburgh Cancer Research Centre Institute of Genomics and Cancer University of Edinburgh Edinburgh UK Genomic Medicine Group Instituto de Investigacion Sanitaria de Santiago Santiago de Compostela Spain Colon Cancer Genetics Group Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK Danish Institute for Advanced Study Department of Public Health University of Southern Denmark Odense Denmark Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University Medical Center Nashville TN USA Division of Genetics and Epidemiology Institute of Cancer Research London UK Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA Genomic Medicine Institute Cleveland Clinic Cleveland OH USA Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland OH USA Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute Barcelona Spain Oncology Data Analytics Program Catalan Institute of Oncology Barcelona Spain Consortium for Biomedical Research in Epidemiology and Public Health Madrid Madrid Spain Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain Department of Biostatistics School of Public Health University of Washington Seattle WA USA Institute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham UK Department of Public Health Richard Doll Building University of Oxford Oxford UK Department of Biomedical Informatics Vanderbilt University School of Medicine Nashville TN USA Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA Center for Public Health Genomics Department of Public Health Sciences University of Virginia Charlottesville VA USA Department of Populat

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

关键词： Colorectal cancer Epigenomics Genome-wide association studies Transcriptomics

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Fundamental immuneoncogenicity trade-offs define driver mutation fitness (vol 606, pg 172, 2022)

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NATURE 2022年第7914期606卷 E5-E5页

作者： Hoyos, David Zappasodi, Roberta Schulze, Isabell Sethna, Zachary de Andrade, Kelvin Cesar Bajorin, Dean F. Bandlamudi, Chaitanya Callahan, Margaret K. Funt, Samuel A. Hadrup, Sine R. Holm, Jeppe S. Rosenberg, Jonathan E. Shah, Sohrab P. Vazquez-Garcia, Ignacio Weigelt, Britta Wu, Michelle Zamarin, Dmitriy Campitelli, Laura F. Osborne, Edward J. Klinger, Mark Robins, Harlan S. Khincha, Payal P. Savage, Sharon A. Balachandran, Vinod P. Wolchok, Jedd D. Hellmann, Matthew D. Merghoub, Taha Levine, Arnold J. Luksza, Marta Greenbaum, Benjamin D. Computational Oncology Department of Epidemiology & Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Swim Across America Laboratory and Ludwig Collaborative Immunology Program Parker Institute for Cancer Immunotherapy Memorial Sloan Kettering Cancer Center New York NY USA Department of Medicine Weill Cornell Medical College New York NY USA Parker Institute for Cancer Immunotherapy Memorial Sloan Kettering Cancer Center New York NY USA Immunology and Microbial Pathogenesis Program Weill Cornell Graduate School of Medical Sciences New York NY USA Hepatopancreatobiliary Service Department of Surgery Memorial Sloan Kettering Cancer Center New York NY USA Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA Division of Cancer Epidemiology and Genetics Clinical Genetics Branch National Cancer Institute National Institutes of Health Rockville MD USA Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA Kravis Center for Molecular Oncology Memorial Sloan Kettering Cancer Center New York NY USA Experimental and Translational Immunology Health Technology Technical University of Denmark Lyngby Denmark Physiology Biophysics & Systems Biology Weill Cornell Medicine Weill Cornell Medical College New York NY USA Department of Surgery Memorial Sloan Kettering Cancer Center New York NY USA Adaptive Biotechnologies Seattle WA USA David M. Rubenstein Center for Pancreatic Cancer Research Memorial Sloan Kettering Cancer Center New York NY USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York NY USA Thoracic Oncology Service Memorial Sloan Kettering Cancer Center New York NY USA Simons Center for Systems Biology Institute for Advanced Study Princeton NJ USA Department of Oncological Sciences Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY USA

Missense driver mutations in cancer are concentrated in a few hotspots1. Various mechanisms have been proposed to explain this skew, including biased mutational processes2, phenotypic differences3,4,5,6 and immunoediting of neoantigens7,8; however, to our knowledge, no existing model weighs the relative contribution of these features to tumour evolution. We propose a unified theoretical ‘free fitness’ framework that parsimoniously integrates multimodal genomic, epigenetic, transcriptomic and proteomic data into a biophysical model of the rate-limiting processes underlying the fitness advantage conferred on cancer cells by driver gene mutations. Focusing on TP53, the most mutated gene in cancer1, we present an inference of mutant p53 concentration and demonstrate that TP53 hotspot mutations optimally solve an evolutionary trade-off between oncogenic potential and neoantigen immunogenicity. Our model anticipates patient survival in The Cancer Genome Atlas and patients with lung cancer treated with immunotherapy as well as the age of tumour onset in germline carriers of TP53 variants. The predicted differential immunogenicity between hotspot mutations was validated experimentally in patients with cancer and in a unique large dataset of healthy individuals. Our data indicate that immune selective pressure on TP53 mutations has a smaller role in non-cancerous lesions than in tumours, suggesting that targeted immunotherapy may offer an early prophylactic opportunity for the former. Determining the relative contribution of immunogenicity and oncogenic function to the selective advantage of hotspot mutations thus has important implications for both precision immunotherapies and our understanding of tumour evolution.

关键词： Computational models Evolutionary theory Tumour immunology Tumour-suppressor proteins

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Telehealth as a Means of Enabling Health Equity

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Yearbook of Medical Informatics 2022年第1期31卷 60-66页

作者： Kuziemsky, Craig Hunter, Inga Udayasankaran, Jai Ganesh Ranatunga, Prasad Kulatunga, Gumindu John, Sheila John, Oommen Flórez-Arango, José F. Ito, Marcia Ho, Kendall Gogia, Shahi B. Araujo, Kleber Rajput, Vije Kumar Meijer, Wouter J. Basu, Arindam MacEwan University Edmonton AB Canada Massey University New Zealand Sri Sathya Sai Central Trust India Provincial Department of Health Services North-Western Province Sri Lanka Health Information Unit Ministry of Health Sri Lanka Sankara Nethralaya Chennai India George Institute for Global Health UNSW New Delhi India Department of Epidemiology and Biostatistics CUNY Graduate School of Public Health New York NY United States Professional Master's Program in Productive Systems Centro Estadual de Educação Tecnológica Paula Souza São Paulo Brazil Department of Emergency Medicine Faculty of Medicine University of British Columbia Vancouver BC Canada Society for Administration of Telemedicine and Healthcare Informatics (SATHI) New Delhi India NUTES - Núcleo de Telessaúde Universidade Federal de Pernambuco Brazil Keele University Staffordshire United Kingdom Quality Assurance eHealth Netherlands School of Health Sciences University of Canterbury New Zealand

Objective: The goal of this paper is to provide a consensus review on telehealth delivery prior to and during the COVID-19 pandemic to develop a set of recommendations for designing telehealth services and tools that contribute to system resilience and equitable health. Methods: The IMIA-Telehealth Working Group (WG) members conducted a two-step approach to understand the role of telehealth in enabling global health equity. We first conducted a consensus review on the topic followed by a modified Delphi process to respond to four questions related to the role telehealth can play in developing a resilient and equitable health system. Results: Fifteen WG members from eight countries participated in the Delphi process to share their views. The experts agreed that while telehealth services before and during COVID-19 pandemic have enhanced the delivery of and access to healthcare services, they were also concerned that global telehealth delivery has not been equal for everyone. The group came to a consensus that health system concepts including technology, financing, access to medical supplies and equipment, and governance capacity can all impact the delivery of telehealth services. Conclusion: Telehealth played a significant role in delivering healthcare services during the pandemic. However, telehealth delivery has also led to unintended consequences (UICs) including inequity issues and an increase in the digital divide. Telehealth practitioners, professionals and system designers therefore need to purposely design for equity as part of achieving broader health system goals. © 2022 IMIA and Georg Thieme Verlag KG.

关键词： equity health systems resilience Telehealth unintended consequences

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Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures

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Nature Communications 2025年第1期16卷 1-13页

作者： Yon Ho Jee Alkes L. Price Peter Kraft Ying Wang Alicia R. Martin Keum Ji Jung Ji-Young Lee Heejin Kimm Rui Duan Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USA Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA USA Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Trans-Divisional Research Program Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Boston MD USA Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA Stanley Center for Psychiatric Research and Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Department of Medicine Harvard Medical School Boston MA USA Institute for Health Promotion Department of Epidemiology and Health Promotion Graduate School of Public Health Yonsei University Seoul Korea

Genome-wide association studies (GWAS) have predominantly focused on European ancestry populations, limiting biological discoveries across diverse populations. Here we report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 301 previously unreported genetic loci in KCPS2, including an association between thyroid-stimulating hormone andCD36. Meta-analysis with the Korean Genome and epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 4588 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotropic missense variant inALDH2, which fine-mapping identified as a likely causal variant for multiple traits. Our findings provide insights into the genetic architecture of complex traits in East Asian populations and highlight how broadening the population diversity of GWAS samples can aid discovery.

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Accuracy of a new rapid diagnostic test for urinary antigen detection and assessment of drug treatment in opisthorchiasis

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Infectious Diseases of Poverty 2023年第6期12卷 79-90页

作者： Chanika Worasith Jiraporn Sithithaworn Phattharaphon Wongphutorn Chutima Homwong Kanoknan Khongsukwiwat Anchalee Techasen Kulthida Y.Kopolrat Watcharin Loilome Nisana Namwat Bandit Thinkamrop Chaiwat Tawarungruang Attapol Titapun Thewarach Laha Ross H.Andrews Simon D.Taylor‑Robinson Paiboon Sithithaworn Department of Adult Nursing Faculty of NursingKhon Kaen UniversityKhon KaenThailand Cholangiocarcinoma Research Institute Khon Kaen UniversityKhon KaenThailand Faculty of Associated Medical Sciences Khon Kaen UniversityKhon KaenThailand Biomedical Science Program Graduate SchoolKhon Kaen UniversityKhon KaenThailand Faculty of Public Health Kasetsart University Chalermphrakiat Sakon Nakhon Province CampusSakon NakhonThailand Department of Systems Biosciences and Computational Medicine Faculty of MedicineKhon Kaen UniversityKhon KaenThailand Khon Kaen University Phenome Centre Khon Kaen UniversityKhon KaenThailand Department of Epidemiology and Biostatistics Faculty of Public HealthKhon Kaen UniversityKhon KaenThailand Department of Surgery Faculty of MedicineKhon Kaen UniversityKhon KaenThailand Depart‑ment of Parasitology Faculty of MedicineKhon Kaen UniversityKhon KaenThailand Faculty of Medicine St Mary’s CampusImperial College LondonLondonUK Division of Digestive Health Department of Surgery and Can‑cerImperial College LondonLondonUK

Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique(FECT)and Kato-Katz *** the urinary enzyme-linked immunosorbent assay(ELISA)has been used more recently,we developed a urinary antigen-based rapid diagnostic test(RDT)to simplify diagnosis and as a point-of-care testing(POCT)and field applications for surveillance and control of *** A urinaryOpisthorchis viverrini(OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against *** diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA(n=493).Cross-reactivities of urinary OV-RDT with other helminthiases coexisted *** were determined(n=96).A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis(n=1629).The McNemar chi-square,Kruskal-Wallis and Cohen’s kappa coefficient(κ-value)tests were used for statistical *** Urinary OV-RDT had sensitivity of 94.2%and specificity of 93.2%,compared to faecal *** OV-RDT had high diagnostic agreement(Kappa=0.842-0.874,P<0.001)and quantitative correlation with urinary antigen ELISA(Kruskal-Wallis tests=316.2,P<0.0001)and faecal FECT(Kruskal-Wallis tests=362.3,P<0.0001).The positive rates by OV-RDT,ELISA and FECT were 48.9%,52.5%and 49.3%,***-reactions of urinary OV-RDT with other helminthiases were few(2%).Field trials of urinary OV-RDT yielded comparable prevalence *** between urinary OV-RDT(53.2%)and urinary antigen ELISA(54.0%).OV screening showed high diagnostic agreement(kappa>0.8,P<0.0001)between urinary OV-RDT and urinary antigen *** cure rates of opisthorchiasis at 1 month post-praziq

关键词： Liver fluke Opisthorchis viverrini Urinary antigen detection Urinary Opisthorchis viverrini rapid diagnosis test Enzyme-linked immunosorbent assay Quantitative formalin-ethyl acetate concentration technique

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Correction: PrEP Uptake and Methamphetamine Use Patterns in a 4-Year U.S. National Prospective Cohort Study of Sexual and Gender Minority People, 2017-2022

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AIDS and behavior 2024年第6期28卷 2087-2088页

作者： Yan Guo Drew A Westmoreland Alexa B D'Angelo Chloe Mirzayi Michelle Dearolf Meredith Ray Pedro B Carneiro David W Pantalone Adam W Carrico Viraj V Patel Sarit A Golub Sabina Hirshfield Donald R Hoover Denis Nash Christian Grov Graduate School of Public Health and Health Policy City University of New York 55 W 125th St 7th Floor mailroom New York NY 10027 USA. Institute for Implementation Science in Population Health City University of New York New York NY USA. Department of Epidemiology College of Medicine College of Public Health and Health Professions University of Florida Gainesville FL USA. Division of Epidemiology Biostatistics and Environmental Health School of Public Health University of Memphis Memphis TN USA. Department of Psychology University of Massachusetts Boston Boston MA USA. The Fenway Institute Fenway Health Boston MA USA. Department of Health Promotion & Disease Prevention Robert Stempel College of Public Health and Social Work Florida International University Miami FL USA. Division of General Internal Medicine Department of Medicine Albert Einstein College of Medicine Montefiore Health System Bronx Miami NY USA. Hunter HIV/AIDS Research Team Department of Psychology Hunter College City University of New York New York NY USA. Department of Medicine STAR Program SUNY Downstate Health Sciences University Brooklyn NY USA. Department of Statistics and Biostatistics Rutgers University New Brunswick NJ USA. Graduate School of Public Health and Health Policy City University of New York 55 W 125th St 7th Floor mailroom New York NY 10027 USA. christian.grov@sph.cuny.edu. Institute for Implementation Science in Population Health City University of New York New York NY USA. christian.grov@sph.cuny.edu.

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