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Immobilization of poly(hexamethylene biguanide) to cellulose acetate- and cellulose-based nanofiber membranes for antibacterial and cytotoxic studies

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Biochemical Engineering Journal 2024年 205卷

作者： dinh Thi My Huong Chi-Yun Wang Pin-Yi Chen Chien Wei Ooi Xue Er Crystal Thew Bing-Lan Liu Chen-Yaw Chiu Shen-Long Tsai Kuei-Hsiang Chen Yu-Kaung Chang Department Chemical Technology and Environment University of Technology and Education the University of Da Nang Da Nang City Viet Nam Department Chemical Engineering/ Graduate School of Biochemical Engineering Ming Chi University of Technology New Taipei City 243303 Taiwan Department Chemical Engineering National Taiwan University of Science and Technology Taipei City 10607 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Bone and Joint Research Centre Chang Gung Memorial Hospital Taoyuan City 333423 Taiwan Research Center for Intelligent Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Chemical Engineering Department School of Engineering Monash University Malaysia Jalan Lagoon Selatan Bandar Sunway Selangor 47500 Malaysia Advanced Engineering Platform School of Engineering Monash University Malaysia Jalan Lagoon Selatan 47500 Bandar Sunway Selangor Malaysia Department of Applied Chemistry Chaoyang University of Technology Taichung 413310 Taiwan Department of Chemical Engineering and Materials Science Yuan Ze University Zhongli Dist Taoyuan City 320315 Taiwan

To develop the environmental antibacterial membrane, the physical attachments of poly (hexamethylene biguanide) hydrochloride (phMB) on the cellulose acetate (CA) and regenerated cellulose (RC) electrospun nanofiber membranes were employed. The immobilization of phMB increased the antibacterial efficacy ( AE , %) of nanofiber membranes from 65.67% to approximately 86.13% for CA-phMB and from 35.09% to approximately 100% for RC-phMB. The results of the chemical and physical characteristics indicate that the degree of deacetylation of CA nanofiber, the surface charge of the nanofiber, and the density of phMB immobilized onto the nanofiber primarily affect the antibacterial efficacy. The use of mathematical models, such as the Temkin equilibrium model for phMB immobilization and the Monod-type model for the relationship between antibacterial activity and immobilization density of phMB provides a deeper understanding of the interactions and kinetics involved. The rapid achievement of ∼100% AE after only 10 min of contact with Escherichia coli ( E. coli ) is a notable finding, indicating the quick and efficient antibacterial action of RC-phMB nanofiber membranes. Furthermore, maintaining approximately 100% AE after 20 days of storage underscores the long-term stability of phMB immobilized on RC nanofiber membranes. The findings suggest that RC-phMB holds great promise as an antibacterial material for biomedical applications, food packaging industries, and filtration or treatment of water.

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Pruritus and Its Association With Cancer and Mortality in dermatomyositis and Polymyositis: A Nationwide Cohort Study in Taiwan From 2005 to 2022

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dermatologic Therapy 2025年第1期2025卷

作者： der-Jr Huang Yu-Hsuan Joni Shao Yi-Hsien Shih Woan-Ruoh Lee Ling-Ya Huang Yu-Min Kuo Quoc Thao Trang pham Hao-Jui Weng Department of Dermatology Taipei Medical University-Shuang Ho Hospital New Taipei City Taiwan shh.org.tw Graduate Institute of Biomedical Informatics College of Medical Science and Technology Taipei Medical University Taipei Taiwan tmu.edu.tw Clinical Big Data Research Center Taipei Medical University Hospital Taipei Taiwan tmuh.org.tw Health Data Analytics and Statistics Center Office of Data Science Taipei Medical University Taipei Taiwan tmu.edu.tw Department of Dermatology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan tmu.edu.tw Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan tmu.edu.tw Division of Allergy Immunology and Rheumatology Department of Internal Medicine National Taiwan University Hospital and National Taiwan University Taipei Taiwan ntu.edu.tw Graduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei Taiwan ntu.edu.tw International Ph.D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei Taiwan tmu.edu.tw Department of Dermatology Faculty of Medicine University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City Vietnam hcmut.edu.vn Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan medcol.mw

Background: Pruritus is the most common initial symptom reported by patients with dermatomyositis (dM) and polymyositis (PM). However, there is limited data regarding the impact of pruritus on cancer and mortality in patients with dM and PM. In this study, we aimed to investigate how pruritus is associated with cancer and mortality in patients with dM and PM. Methods: This nationwide, population-based retrospective cohort study included adult dM and PM patients from Taiwan’s National Health Insurance Research database between 2005 and 2022. Sex- and age-matched pruritic patients, identified by over 6 weeks of antipruritic medication use, and nonpruritic patients were analyzed. The primary outcome was cancer occurrence or all-cause mortality. The association between pruritus and these outcomes was estimated using Cox proportional hazards models. Results: Among 919 matched pairs of pruritic and nonpruritic patients, cancer was observed in 19.96% in the long-term pruritic group (LPG), 14.63% in the short-term pruritic group (SPG), and 10.34% in the non-pruritic group (NPG) ( p < 0.0001). All-cause mortality was documented as 30.37% in the LPG, 29.69% in the SPG, and 37.76% in the NPG ( p < 0.0001). After adjusting for sex, age, and other comorbidities, pruritus was associated with an increased risk of cancer (hazard ratio (HR) 1.708, 95% confidence interval (CI) 1.229–2.374) and a lower risk of all-cause mortality (HR 0.483, 95% CI 0.409–0.569). Conclusion: This population-based study revealed that pruritus appeared to be associated with increased risks of cancer and decreased all-cause mortality. Thus, pruritus may serve as a pragmatic factor for risk stratification and tailored treatment strategies in dM and PM. Cancer screening, particularly for nasopharyngeal and breast cancers in East Asian populations, is recommended for patients with dM or PM, especially those presenting with pruritus. Meanwhile, patients without pruritus may require vigilant management for pote

关键词： cancer dermatomyositis idiopathic inflammatory myopathies mortality polymyositis pruritus

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The Production of Black ph.d.’s in Economics at Harvard University, 1905–1955

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Review of Black Political Economy 2017年第1-2期44卷 167-201页

作者： Myers, Samuel L. Humphrey School of Public Affairs University of Minnesota 301 19th Avenue South Minneapolis 55455 MN United States Graduate Faculty Applied Economics Ph.D. Program University of Minnesota 301 19th Avenue South Minneapolis 55455 MN United States

Harvard University’s Economics department produced some of the leading African American economists between World War I and the Korean War. This essay explores the factors that contributed to this accomplishment and documents the career trajectories of the six blacks who obtained the doctorate in Economics from Harvard University during the period 1905–1955. The analysis reveals the pivotal roles of the Rosenwald Fund, Classical High Schools, Black Fraternal Organizations and former University of Minnesota applied Economics Professor, John d. Black. A common outcome of the careers of these six pioneers was a commitment to black economic empowerment. © 2017, Springer Science+Business Media New York.

关键词： Black economists Booker T. McGraw Harvard University ph.d. program in economics Hastings dudley Huggins History of economic thought John d. Black John d. Black, University of Minnesota Robert Weaver Samuel Lloyd Myers, Sr Samuel Z. Westerfield, Jr William H. dean, Jr

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Ovatodiolide and antrocin synergistically inhibit the stemness and metastatic potential of hepatocellular carcinoma via impairing ribosome biogenesis and modulating ERK/Akt-mTOR signaling axis

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phytomedicine : international journal of phytotherapy and phytopharmacology 2023年 108卷 154478页

作者： Ming-Yao Chen Chia-Hung Hsu Syahru Agung Setiawan david T W Tzeng Hon-Ping Ma Jiann Ruey Ong Yi Cheng Chu Ming-Shou Hsieh Alexander T H Wu Yew-Min Tzeng Chi-Tai Yeh Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei City 110 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Taipei Medical University-Shuang Ho Hospital New Taipei City 235 Taiwan. Department of Emergency Medicine Taipei Medical University-Shuang Ho Hospital New Taipei City 235 Taiwan Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei City 110 Taiwan Department of Emergency Medicine School of Medicine Taipei Medical University Taipei City 110 Taiwan. International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei City 110 Taiwan Department of Medical Research & Education Taipei Medical University - Shuang-Ho Hospital New Taipei City 235 Taiwan. School of Life Sciences The Chinese University of Hong Kong Hong Kong SAR 999077 China Lifebit Mindspace Shoreditch London England EC2A 2AP UK. Department of Medicine St. George's University School of Medicine St. George Grenada. Department of Applied Science National Taitung University Taitung 95092 Taiwan. Electronic address: ymtzeng@nttu.edu.tw. Department of Medical Research & Education Taipei Medical University - Shuang-Ho Hospital New Taipei City 235 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan. Electronic address: ctyeh@s.tmu.edu.tw.

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combi

关键词： Advanced HCC Antrocin (ANC) MAPK Ovatodiolide (OVA) PI3K

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Unsupervised extraction of phenotypes from cancer clinical notes for association studies

arXiv

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arXiv 2019年

作者： Stark, Stefan G. Hyland, Stephanie L. Pradier, Melanie F. Lehmann, Kjong-Van Wicki, Andreas Perez-Cruz, Fernando Vogt, Julia E. Rätsch, Gunnar Computational Biology Program Memorial Sloan Kettering Cancer Center New York United States Tri-Institutional Ph.D. Program in Computational Biology and Medicine Weill Cornell Medicine New York United States Department of Computer Science ETH Zürich Zürich Switzerland Medical Informatics Group University Hospital Zürich Zürich Switzerland Swiss Institute for Bioinformatics Zurich Switzerland Department of Biology ETH Zürich Zürich Switzerland Department of Signal Processing and Information Theory University Carlos III in Madrid Leganés Spain School of Engineering and Applied Sciences Harvard University CambridgeMA United States Department of Biomedicine University of Basel Basel Switzerland Tumorzentrum University Hospital Basel Basel Switzerland Swiss Data Science Center ETH Zürich and EPFL Lausanne Switzerland Department of Mathematics and Computer Science University of Basel Basel Switzerland

The recent adoption of Electronic Health Records (EHRs) by healthcare providers has introduced an important source of data that provides detailed and highly specific insights into patient phenotypes over large cohorts. These datasets, in combination with machine learning and statistical approaches, generate new opportunities for research and clinical care. However, many methods require the patient representations to be in structured formats, while the information in the EHR is often locked in unstructured text designed for human readability. In this work, we develop the methodology to automatically extract clinical features from clinical narratives from large EHR corpora without the need for prior knowledge. We consider medical terms and sentences appearing in clinical narratives as atomic information units. We propose an efficient clustering strategy suitable for the analysis of large text corpora and utilize the clusters to represent information about the patient compactly. Additionally, we define the sentences on ontologic and natural language vocabularies to automatically detect pertinent combinations of concepts present in the corpus, even when an ontology is not available. To demonstrate the utility of our approach, we perform an association study of clinical features with somatic mutation profiles from 4,007 cancer patients and their tumors. We apply the proposed algorithm to a dataset consisting of .65 thousand documents with a total of .3.2 million sentences. After correcting for cancer type and other confounding factors, we identify a total of 340 significant statistical associations between the presence of somatic mutations and clinical features. We annotated these associations according to their novelty and we report several known associations. We also propose 37 plausible, testable hypothesis for associations where the underlying biological mechanism does not appear to be known. These results illustrate that the automated discovery of clinical features

关键词： diseases

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Self-Reflection as an Assessment of Student Preparation for Practice in Humanitarian Crises

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Practicing Anthropology 2022年第3期44卷

作者： Krista E. Latham Isabel S. Melhado Olivia H. Messenger Tanya Ramos Alex F. Wong a Krista E. Latham (lathamke@uindy.edu) is a Professor of Biology and Anthropology in the Shaheen College of Arts and Sciences at the University of Indianapolis. She obtained her Ph.D. and M.A. in anthropology from Temple University her M.S. in human biology from the University of Indianapolis and her B.S. in biology and chemistry from the University of North Texas. She is also the director of the University of Indianapolis Human Identification Center and a Board-Certified Forensic Anthropologist. Latham’s research interests include investigations of human genetic and skeletal variation forensic osteology forensic archeology and the sociopolitics of forensic science. b Isabel S. Melhado (melhadoi@uindy.edu) is a graduate student at the University of Indianapolis studying Human Biology with a concentration in forensic anthropology. She has a B.S. in Biology with a concentration in forensic science and a minor in anthropology from Northwestern State University of Louisiana. Her research interests include forensic and biological anthropology human identification human rights and ethics ancestry assessment from skeletal remains and forensic DNA analysis. c Olivia H. Messenger (messengero@uindy.edu) is a graduate student in the Human Biology program at the University of Indianapolis. She has a B.A. in Anthropology and minors in Biology and Arabic from Indiana University - Purdue University Indianapolis. Her research interests include sexual dimorphism identification techniques and forensic science in human rights settings. d Tanya Ramos (ramost@uindy.edu) is a graduate student at the University of Indianapolis studying human biology with a concentration in forensic anthropology. She received a B.A. in Anthropology from the University of Nevada Las Vegas in 2017. Her research interests include biological/forensic anthropology human identification human rights and ethics. e Alex F. Wong (wongaf@uindy.edu) is an M.S. Candidate in the Human Biology program (Concentration in Forensic Anthropology) at the Unive

This article explores the impact of a critical pedagogy of forensic science approach combined with an immersive field experience to train student members of a volunteer humanitarian forensic science team in preparation for immersion in the politically charged and emotionally challenging conditions surrounding migrant death at the United States-Mexico Border. Utilizing self-reflections from student team members before and after their fieldwork, the impact of a holistic and multi-faceted training approach can be evaluated. The goal of this training approach is to produce capable forensic scientists, as well as anthropologists who recognize the power structures inherent in such situations and subsequently work to kindle social change. Comparing expectations before fieldwork to experiences obtained during fieldwork can be a powerful way to gauge their progress in a transformative learning process.

关键词： forensic anthropology critical pedagogy self-reflection

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Adaptive fuzzy sliding mode active vibration control for rail vehicle pantograph

Adaptive fuzzy sliding mode active vibration control for rai...

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IEEE International Conference on Fuzzy Systems (FUZZ-IEEE)

作者： Tsung-Chih Lin Jian-Lin Yeh Chia-Hao Kuo Yu-Chen Lin Valentina E. Balas Department of Electronic Engineering Feng-Chia University Taichung Taiwan Ph.D. Program of Electrical and Communications Engineering Feng-Chia University Taichung Taiwan Department of Automatic Control Engineering Feng Chia University Taichung Taiwan Department of Automation and Applied Informatics Aurel Vlaicu University of Arad Arad Romania

ISBN: (纸本)9781509006274

In this paper, the uncertain dynamic active pantograph-catenary system which considers the effect of time-varying stiffness resulting from the uneven overhead wire is investigated to improve current collection for light rail vehicle. In order to achieve stable current collection, and hence improve the performance of the overall electricity supply, sliding mode control strategy and adaptive fuzzy sliding mode control scheme are combined. The uplift force which is applied to pantograph frame by actuator is constructed by incorporating fuzzy neural network (FNN) and sliding mode control to attenuate the chattering problem resulting from the sliding mode control. Based on the Lyapunov stability theorem, the active control law and adaptive laws for the free parameters of the FNNs can be derived to effectively suppress vibration of the pantograph system.

关键词： Force Cats dynamics Wires Sliding mode control Fuzzy neural networks Fuzzy control

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Investigating the main operating mechanism of the zinc oxide layer of ZnO RRAM

Investigating the main operating mechanism of the zinc oxide...

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International Symposium on Computer, Consumer and Control

作者： Xin-tian Zhao Chun-Mei Lu Shao-Wen Su Hsin-Chiang You Cheng-Yen Wu Wen-Luh Yang College of Electrical and Control Engineering Xi'an University of Science and Technology Department of Chemical and Materials Engineering National Chin-Yi University of Technology Department of Applied English National Chin-Yi University of Technology Department of Electronic Engineering National Chin-Yi University of Technology Ph.D. Program of Electrical and Communications Engineering Feng Chia University Department of Electronic Engineering Feng Chia University

ISBN: (纸本)9781509030729

This study is to investigate the main operating mechanism of zinc oxide layer of ZnO RRAM (Resistance Random Access Memory). This experiment prepared four types of ZnO RRAM under different thermal annealing temperatures, Keithley 4200 measurement system was used to measure the operating voltage and current under a high impedance state and a low resistance state into the dielectric layer transmission mechanism analysis. This study found that the operating mechanism of a zinc oxide layer under the low-resistance state is mainly ohm conduction state. However, the operating mechanism of a zinc oxide layer under the high-resistance state is Poole-Frenkel Emission.

关键词： Zinc oxide layer Thermal annealing temperature Ohm conduction Poole - Frank Emission

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Publisher Correction: Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020

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Eye (London, England) 2024年第11期38卷 2229-2231页

作者： Konrad Pesudovs Hugh R. Taylor Tabassom Sedighi Rupert R. A. Bourne Shahina Pardhan Van Charles Lansingh John H. Kempen Ian Tapply Arthur G. Fernandes Maria Vittoria Cicinelli Alessandro Arrigo Nicolas Leveziel Serge Resnikoff Seth Flaxman Mukkharram M. Bikbov Tasanee Braithwaite Alain Bron Ching-Yu Cheng Monte A. del Monte Joshua R. Ehrlich Leon B. Ellwein david Friedman João M. Furtado Gus Gazzard Ronnie George M. Elizabeth Hartnett Jost B. Jonas Rim Kahloun Moncef Khairallah Rohit C. Khanna Janet Leasher Julie-Anne Little Vinay Nangia Michal Nowak Tunde Peto Pradeep Ramulu Fotis Topouzis Mitiadis Tsilimbaris Ya Xing Wang Ningli Wang Paul Svitil Briant Theo Vos Katrin Burkart Kaleb Coberly Xiaochen dai Stephen S. Lim Tomislav Mestrovic Ali H. Mokdad Christopher J. L. Murray Jaimie d. Steinmetz Awoke Misganaw Yohannes Habtegiorgis Abate Mohammad Abdollahi Mozhan Abdollahi Ayele Mamo Abebe Olumide Abiodun Richard Gyan Aboagye Woldu Aberhe Abrha Hasan Abualruz Hiwa Abubaker Ali Eman Abu-Gharbieh Salahdein Aburuz Tadele Girum Girum Adal Mesafint Molla Adane Isaac Yeboah Addo Qorinah Estiningtyas Sakilah Adnani Muhammad Sohail Afzal Muhammad Umair Shahin Aghamiri Bright Opoku Ahinkorah Aqeel Ahmad Sajjad Ahmad Ali Ahmadi Siamak Sabour Ayman Ahmed Haroon Ahmed Ahmad Samir Alfaar Abid Ali Syed Shujait Shujait Ali Awais Altaf Hubert Amu Emmanuel Manu Sofia Androudi Rodrigo Anguita Abhishek Anil Rimple Jeet Kaur Muhammad Aaqib Shamim Saeid Anvari Anayochukwu Edward Anyasodor Francis Appiah Jalal Arabloo Haleh Ayatollahi Mosab Arafat damelash Areda Reza Arefnezhad Brhane Berhe Aregawi Akeza Awealom Asgedom Tahira Ashraf Seyyed Shamsadin Athari Bantalem Tilaye Tilaye Atinafu Birhan Tsegaw Taye Maha Moh’d Wahbi Atout Alok Atreya Ahmed Y. Azzam Hassan Babamohamadi Sara Bagherieh Yogesh Bahurupi Atif Amin Baig Shumaila Nargus Biswajit Banik Mainak Bardhan Saurav Basu Kavita Batra Nebiyou Simegnew Bayileyegn Fatemeh Bazvand Addisu Shunu Beyene Awoke Masrie Asrat derese devidas S. Bhagat Akshaya Srikanth Bhagavathula Pankaj Bh Medicine & Health University of New South Wales Sydney NSW Australia School of Optometry and Vision Science University of New South Wales Sydney NSW Australia School of Population and Global Health University of Melbourne Carlton VIC Australia Vision and Eye Research Institute Anglia Ruskin University Cambridge UK HelpMeSee Instituto Mexicano de Oftalmologia Santiago de Querétaro Mexico University of Miami Gables FL USA University of Utah Salt Lake City UT USA Chief Medical Office HelpMeSee New York NY USA Mexican Institute of Ophthalmology Queretaro Mexico Department of Ophthalmology Massachusetts Eye and Ear/Shepens Eye Research Institute/Harvard Medical School Boston MA USA Eye Unit MyungSung Christian Medical Center (MCM) Comprehensive Specialized Hospital and MyungSun Medical College Addis Ababa Ethiopia Department of Ophthalmology Addis Ababa University Addis Ababa Ethiopia Sight for Souls Bellevue WA USA Department of Ophthalmology Harvard University Boston MA USA Eye Unit MyungSung Medical College Addis Ababa Ethiopia Addenbrooke’s Hospital Cambridge UK Department of Ophthalmology Cambridge University Hospitals Cambridge UK Federal University of Sao Paolo Sao Paolo SP Brazil University of Calgary Calgary AB Canada Department of Ophthalmology and Visual Sciences Federal University of São Paulo Sao Paulo Brazil School of Medicine Vita-Salute San Raffaele University Milan Italy Department of Ophthalmology IRCCS San Raffaele Scientific Institute Milan Italy Department of Ophthalmology San Raffaele Scientific Institute Milano Italy IRCCS San Raffaele Scientific Institute Vita-Salute University Milan Italy Scientific Institute San Raffaele Hospital Vita-Salute University Milan Italy University of Poitiers Poitiers France CHU de Poitiers Poitiers France Ophthalmology Department CHU de Poitiers (Poitiers University Hospital) Poitiers France Unité 1084 National Institute of Health and Medical Research (INSERM) Poitiers France

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Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

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Nature communications 2023年第1期14卷 3043页

作者： Jianxin Shi Kouya Shiraishi Jiyeon Choi Keitaro Matsuo Tzu-Yu Chen Juncheng dai Rayjean J Hung Kexin Chen Xiao-Ou Shu Young Tae Kim Maria Teresa Landi dongxin Lin Wei Zheng Zhihua Yin Baosen Zhou Bao Song Jiucun Wang Wei Jie Seow Lei Song I-Shou Chang Wei Hu Li-Hsin Chien Qiuyin Cai Yun-Chul Hong Hee Nam Kim Yi-Long Wu Maria Pik Wong Brian douglas Richardson Karen M Funderburk Shilan Li Tongwu Zhang Charles Breeze Zhaoming Wang Batel Blechter Bryan A Bassig Jin Hee Kim demetrius Albanes Jason Y Y Wong Min-Ho Shin Lap Ping Chung Yang Yang She-Juan An Hong Zheng Yasushi Yatabe Xu-Chao Zhang Young-Chul Kim Neil E Caporaso Jiang Chang James Chung Man Ho Michiaki Kubo Yataro daigo Minsun Song Yukihide Momozawa Yoichiro Kamatani Masashi Kobayashi Kenichi Okubo Takayuki Honda dean H Hosgood Hideo Kunitoh Harsh Patel Shun-Ichi Watanabe Yohei Miyagi Haruhiko Nakayama Shingo Matsumoto Hidehito Horinouchi Masahiro Tsuboi Ryuji Hamamoto Koichi Goto Yuichiro Ohe Atsushi Takahashi Akiteru Goto Yoshihiro Minamiya Megumi Hara Yuichiro Nishida Kenji Takeuchi Kenji Wakai Koichi Matsuda Yoshinori Murakami Kimihiro Shimizu Hiroyuki Suzuki Motonobu Saito Yoichi Ohtaki Kazumi Tanaka Tangchun Wu Fusheng Wei Hongji dai Mitchell J Machiela Jian Su Yeul Hong Kim In-Jae Oh Victor Ho Fun Lee Gee-Chen Chang Ying-Huang Tsai Kuan-Yu Chen Ming-Shyan Huang Wu-Chou Su Yuh-Min Chen Adeline Seow Jae Yong Park Sun-Seog Kweon Kun-Chieh Chen Yu-Tang Gao Biyun Qian Chen Wu daru Lu Jianjun Liu Ann G Schwartz Richard Houlston Margaret R Spitz Ivan P Gorlov Xifeng Wu Ping Yang Stephen Lam Adonina Tardon Chu Chen Stig E Bojesen Mattias Johansson Angela Risch Heike Bickeböller Bu-Tian Ji H-Erich Wichmann david C Christiani Gadi Rennert Susanne Arnold Paul Brennan James McKay John K Field Sanjay S Shete Loic Le Marchand Geoffrey Liu Angeline Andrew Lambertus A Kiemeney Shan Zienolddiny-Narui Kjell Grankvist Mikael Johansson Angela Cox Fiona Taylor Jian-Min Yuan philip Lazarus Matthew B Schabath Melinda C Aldrich Hyo-Sung Jeon Shih Sheng Jiang Jae Sook Sung C Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA. jianxin.shi@nih.gov. Division of Genome Biology National Cancer Research Institute Tokyo Japan. Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA. Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan. Institute of Population Health Sciences National Health Research Institutes Zhunan Taiwan. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment Collaborative Innovation Center for Cancer Medicine Nanjing Medical University Nanjing China. Prosserman Centre for Population Health Research Lunenfeld-Tanenbaum Research Institute Sinai Health Toronto ON Canada. Department of Epidemiology and Biostatistics National Clinical Research Center for Cancer Key Laboratory of Molecular Cancer Epidemiology of Tianjin Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University Tianjin China. Division of Epidemiology Department of Medicine Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center Nashville TN USA. Cancer Research Institute Seoul National University College of Medicine Seoul Republic of Korea. Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China. Department of Epidemiology School of Public Health China Medical University Shenyang China. Department of Clinical Epidemiology and Center of Evidence Based Medicine The First Hospital of China Medical University Shenyang China. Department of Oncology Shandong Cancer Hospital and Institute Shandong Academy of Medical Sciences Jinan China. Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai China. S

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FAdS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

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