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Serum organophosphate flame retardants and plasticizers in Chinese females of childbearing age: Association with serum reproductive and thyroid hormones

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Chemosphere 2023年第1期337卷 139237页

作者： Liu, Yarui Li, Yongcheng Xiao, Nan Liu, Min Wang, Yu Luo, Haining Yao, Yiming Feng, Yujie Wang, Shuo College of Environmental Science and Engineering Nankai University 38 Tongyan Road Jinnan District Tianjin300350 China School of Environmental Science and Engineering Academy of Environment and Ecology Tianjin University 92 Weijin Road Nankai District Tianjin300072 China MOE Key Laboratory of Pollution Processes and Environmental Criteria College of Environmental Science and Engineering Nankai University 38 Tongyan Road Jinnan District Tianjin300350 China Department of Center for Reproductive Medicine Tianjin Central Hospital of Gynecology Obstetrics / Tianjin Key Laboratory of Human Development and Reproductive Regulation 156 Nankaisanma Road Nankai District Tianjin300100 China State Key Laboratory of Urban Water Resource and Environment Harbin Institute of Technology No. 73 Huanghe Road Nangang District Harbin150090 China Tianjin Key Laboratory of Food Science and Health School of Medicine Nankai University 94 Weijin Road Nankai District Tianjin300071 China

Organophosphate flame retardants (OPFRs) are extensively used as flame retardants and plasticizers, but their endocrine disrupting potentials have raised concerns. However, the impacts of OPFR exposures on reproductive and thyroid hormones in females remains unclear. In this study, serum concentrations of OPFRs were investigated, and levels of reproductive and thyroid hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone, prolactin (PRL), testosterone (T), and thyroid stimulating hormone, were analyzed in childbearing-age females undergoing in-vitro fertilization treatment from Tianjin, a coastal city in China (n = 319). Tris (2-chloroethyl) phosphate (TCEP) was the predominant OPFR, with a median concentration of 0.33 ng/mL and a detection frequency of 96.6%. In the whole population, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP) were positively associated with T (p © 2023 Elsevier Ltd

关键词： Hormones

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Corrosion Behaviour of Fe-Rgo Composites in Two Different Solutions for Bone Scaffold Applications

SSRN

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SSRN 2025年

作者： Bahrudin, Mohammad Taufiq Al Hakim Zulkarnaini, Nor Amira Syairah Ulum, Mokhamad Fakhrul Nur, Hadi Mohd Szali Januddi, Mohd Al Fatihhi Yusop, Abdul Hakim Md Faculty of Mechanical Engineering Universiti Teknologi Malaysia Johor Malaysia Department of Materials Manufacturing and Industrial Engineering Faculty of Mechanical Engineering Universiti Teknologi Malaysia Johor Malaysia School of Human Resource Development and Psychology Faculty of Social Science and Humanities Universiti Teknologi Malaysia Johor Johor Bharu Malaysia Indonesia Department of Chemistry Faculty of Mathematics and Natural Sciences Universitas Negeri Malang Malang Indonesia Universitas Negeri Malang Malang Indonesia Section Universiti Kuala Lumpur Malaysian Institute of Industrial Technology Johor Masai Malaysia Institut Pertanian Bogor Indonesia

Iron has been increasingly studied over the past decade as a potential material for biodegradable bone implants due to its favorable mechanical strength and degradability. However, its slow corrosion rate in both in vitro and in vivo environments poses a challenge to its use as a temporary medical implant. In this study, the effects of reduced graphene oxide (rGO) addition on the corrosion behavior of an Fe matrix were assessed in two different solutions: phosphate-buffered saline (PBS) and protein-containing cell culture medium (RPMI-Pro). The results indicate a significant difference in the corrosion rate and behavior of Fe-rGO composites, with notably faster degradation observed in RPMI-Pro. Electrochemical and immersion tests revealed that rGO enhances the in vitro corrosion of Fe scaffolds, primarily due to its high surface area and favorable electrical conductivity, which accelerate redox reactions within the scaffolds. The Fe-0.5rGO sample immersed in RPMI-Pro exhibited a higher corrosion rate, as the adsorbed fetal bovine serum (FBS) proteins facilitated Fe dissolution by complexing with Fe ions, thereby preventing the formation of a low-solubility, dense Fe-based oxide passive layer. © 2025, The Authors. All rights reserved.

关键词： Redox reactions

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Chikungunya virus drives gut microbiota shifts and IFN-Mediated intestinal repair: insights into microbiota-immune interplay

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Gut microbes 2025年第1期17卷 2512900页

作者： Hongyu Chen Kaiyun Ding Cong Tang Jingwen Xu Fengyuan Zhang Yao Yan Bai Li Yanan Zhou Yun Yang Hao Yang Qing Huang Wenhai Yu Haixuan Wang Daoju Wu Shuaiyao Lu Hongqi Liu Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC) Kunming Yunnan China. Yunnan Province Science and Technology Department Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development Kunming Yunnan China. National Human Diseases Animal Model Resource Center NHC Key Laboratory of Human Disease Comparative Medicine National Center of Technology Innovation for Animal Model State Key Laboratory of Respiratory Health and Multimorbidity and Key Laboratory of Pathogen Infection Prevention and Control Ministry of Education Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.

Chikungunya virus (CHIKV) infection causes joint damage and gastrointestinal clinical symptoms, including vomiting and diarrhea, particularly in elderly populations, reflecting the potential role of gut immunity in infection. However, the mechanisms by which CHIKV induces gastrointestinal diseases remain largely unexplored. This study investigated the characteristics of fecal and gut microbiota, gut metabolites, and gut immunity post-infection using multi-omics analysis. The role of gut microbiota was further validated through Oral antibiotic depletion (Abx). Importantly, a systematic comparison of age-dependent differences in gut microbiota composition and immune responses following CHIKV infection was conducted to elucidate the involvement of gut microbiota in CHIKV pathogenesis. CHIKV joint inoculation induces gastrointestinal infection and histological damage, drives fluctuations in gut microbiota, markedly increasing the abundance of and . and upregulates conjugates of taurine and bile acids. CHIKV infection further exacerbates systemic inflammatory burden and activates intestinal interferon (IFN) signaling cascades, which supports gut repair and mucosal regeneration, but low antiviral responses to CHIKV infection compared with that of adult animals. Our results suggest that the gastrointestinal tract, along with its microbes and metabolites, modulates CHIKV infection in an age-dependent manner, providing critical insights for diagnosis, treatment, and novel therapeutic development.

关键词： CHIKV gastrointestinal infection gut microbiota integrative analysis interferon

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The effects of applying virtual-reality implementation for reflection after contextual mobile learning 26

The effects of applying virtual-reality implementation for r...

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26th International Conference on Computers in Education, ICCE 2018

作者： Hsu, Ting-Chia Chan, Chuan-Yi Department of Technology Application and Human Resource Development National Taiwan Normal University Taiwan Taipei Municipal Neihu High School Taiwan

ISBN: (纸本)9789869721424

This study integrated Chinese, Geography, and computer science courses, with teachers from those disciplines collaborating to prepare their courses. The study employed mobile devices in the learning activities, used the situated learning strategy, and involved the students in real-life investigation in the interdisciplinary literacy curriculum. The students observed, learning in the real-life environment, and utilized mobile technologies to support their data collection and information searching. The students made connections between the knowledge in the textbook and the real-life situation in the literacy-based learning activities. After they came back to the classroom, they used the data and photos they had collected to design the virtual reality of the environment they had visited in order to recall and reflect on the activity. This study primarily explored the learning effectiveness of Chinese, and found that the students made significant progress. However, from the investigation of motivation, it was found that the students did not prefer to practicing writing based on the virtual reality situation in comparison with the real-life situation. © 2018 Asia-Pacific Society for Computers in Education..All Rights Reserved.

关键词： Virtual reality

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Locus of Control and Usage of Social Media on Academic Achievement Among Police College Students in Taiwan

Locus of Control and Usage of Social Media on Academic Achie...

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2nd International Conference on Innovative Technologies and Learning, ICITL 2019

作者： Kuo, Cheng-Te Chang, Chi-Cheng Yen, Wan-Hsuan Department of Technology Application and Human Resource Development National Taiwan Normal University No. 162 Sec. 1 HePing E. Rd. 106 Taipei Taiwan Police Administration Division Taiwan Police College No. 153 Sec. 3 Xinglong Rd. 116 Taipei Taiwan

ISBN: (纸本)9783030353421

In recent years, owing to the development of mobile devices, people can use social media more conveniently. This new trend of media drastically changes people’s lives, especially among adolescents. Earlier researches suggested it benefits their learning performance but also contains the risk of addiction. This research thus investigated the relationship between the usage of social media and the academic achievement of college students, and whether this would be different among students with the various locus of control. There was a total of 298 students participated in this research. The results are as follows: (1) External locus of control on expanding one’s conduct grade has several significant positive effects. (2) External locus of control on expressing the usage of social media has several significant positive effects. (3) Conduct grade was directly affected by External locus of control, this connection was the full mediation by the use time of social media. Last but not least, we have some suggestions for teachers, parents, and schools. Since using social media is essential for modern life, the following rise and problems from using social media applications or websites exist too. However, social media should not take the blame entirely. It all depends on how you use it. We should teach students to control themselves and use the right way to get better academic results, rather than getting rid of mobile phones and removing social media applications from their mobile phones. We hope that we can find the proper solutions in the future by having more in-depth research and avoid students’ abuse of social media and improve academic achievement. © Springer Nature Switzerland AG 2019.

关键词： Students

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Correction to: Retinoic acid receptor γ activation promotes differentiation of human induced pluripotent stem cells into esophageal epithelium

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Journal of gastroenterology 2020年第10期55卷 1010-1011页

作者： Yasufumi Koterazawa Michiyo Koyanagi-Aoi Keiichiro Uehara Yoshihiro Kakeji Takashi Aoi Division of Advanced Medical Science Graduate School of Science Technology and Innovation Kobe University 7-5-1 Kusunoki-cho Chuo-ku Kobe 650-0017 Japan. Department of iPS Cell Applications Graduate School of Medicine Kobe University Kobe Japan. Division of Gastrointestinal Surgery Department of Surgery Graduate School of Medicine Kobe University Kobe Japan. Center for Human Resource Development for Regenerative Medicine Kobe University Hospital Kobe Japan. Division of Pathology Graduate School of Medicine Kobe University Kobe Japan. Division of Advanced Medical Science Graduate School of Science Technology and Innovation Kobe University 7-5-1 Kusunoki-cho Chuo-ku Kobe 650-0017 Japan. takaaoi@med.kobe-u.ac.jp. Department of iPS Cell Applications Graduate School of Medicine Kobe University Kobe Japan. takaaoi@med.kobe-u.ac.jp. Center for Human Resource Development for Regenerative Medicine Kobe University Hospital Kobe Japan. takaaoi@med.kobe-u.ac.jp.

In the original publication of the article, the following errors were noted and corrected in this correction.

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Automatic assessment of individual culture attribute of power distance using a social context-enhanced prosodic network representation 19

Automatic assessment of individual culture attribute of powe...

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19th Annual Conference of the International Speech Communication, INTERSPEECH 2018

作者： Tsai, Fu-Sheng Yang, Hao-Chun Chang, Wei-Wen Lee, Chi-Chun Department of Electrical Engineering National Tsing Hua University Taiwan International Human Resource Development National Taiwan Normal University Taiwan MOST Joint Research Center for AI Technology All Vista Healthcare Taiwan

Culture is a collective social norm of human societies that often influences a person's values, thoughts, and social behaviors during interactions at an individual level. In this work, we present a computational analysis toward automatic assessing an individual's culture attribute of power distance, i.e., a measure of his/her belief about status, authority and power in organizations, by modeling their expressive prosodic structures during social encounters with people of different power status. Specifically, we propose a center-loss embedded network architecture to jointly consider the effect of social interaction contexts on individuals' prosodic manifestations in order to learn an enhanced representation for power distance recognition. Our proposed prosodic network achieves an overall accuracy of 78.6% in binary classification task of recognizing high versus low power distance. Our experiment demonstrates an improved discrim-inability (17.6% absolute improvement) over prosodic neural network without social context enhancement. Further visualization reveals that the diversity in the prosodic manifestation for individuals with low power distance seems to be higher than those of high power distance. © 2018 International Speech Communication Association. All rights reserved.

关键词： Speech communication

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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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Hearing loss prevalence and years lived with disability, 1990-2019: Findings from the Global Burden of Disease Study 2019

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The Lancet 2021年第10278期397卷 996-1009页

作者： Haile, Lydia M. Kamenov, Kaloyan Briant, Paul Svitil Orji, Aislyn U. Steinmetz, Jaimie D. Abdoli, Amir Abdollahi, Mohammad Abu-Gharbieh, Eman Afshin, Ashkan Ahmed, Haroon Rashid, Tarik Ahmed Akalu, Yonas Alahdab, Fares Alanezi, Fahad Mashhour Alanzi, Turki M. Al Hamad, Hanadi Ali, Liaqat Alipour, Vahid Al-Raddadi, Rajaa M. Amu, Hubert Arabloo, Jalal Arab-Zozani, Morteza Arulappan, Judie Ashbaugh, Charlie Atnafu, Desta Debalkie Babar, Zaheer-Ud-Din Baig, Atif Amin Banik, Palash Chandra Bärnighausen, Till Winfried Barrow, Amadou Bender, Rose G. Bhagavathula, Akshaya Srikanth Bhardwaj, Nikha Bhardwaj, Pankaj Bibi, Sadia Bijani, Ali Burkart, Katrin Cederroth, Christopher R. Charan, Jaykaran Choudhari, Sonali Gajanan Chu, Dinh-Toi Couto, Rosa A.S. Dagnew, Amare Belachew Dagnew, Baye Dahlawi, Saad M.A. Dai, Xiaochen Dandona, Lalit Dandona, Rakhi Desalew, Assefa Dhamnetiya, Deepak Dhimal, Mandira Lamichhane Dhimal, Meghnath Doyle, Kerrie E. Duncan, Bruce B. Ekholuenetale, Michael Filip, Irina Fischer, Florian Franklin, Richard Charles Gaidhane, Abhay Motiramji Gaidhane, Shilpa Gallus, Silvano Ghamari, Farhad Ghashghaee, Ahmad Ghozali, Ghozali Gilani, Syed Amir Glǎvan, Ionela-Roxana Golechha, Mahaveer Goulart, Barbara Niegia Garcia Gupta, Veer Bala Gupta, Vivek Kumar Hamidi, Samer Hammond, Billy Randall Hay, Simon I. Hayat, Khezar Heidari, Golnaz Hoffman, Howard J. Hopf, Kathleen Pillsbury Hosseinzadeh, Mehdi Househ, Mowafa Hussain, Rabia Hwang, Bing-Fang Iavicoli, Ivo Ibitoye, Segun Emmanuel Ilesanmi, Olayinka Stephen Irvani, Seyed Sina Naghibi Islam, Sheikh Mohammed Shariful Iwagami, Masao Jacob, Louis Jayapal, Sathish Kumar Jha, Ravi Prakash Jonas, Jost B. Kalhor, Rohollah Al-Salihi, Nawzad Kameran Kandel, Himal Kasa, Ayele Semachew Kayode, Gbenga A. Khalilov, Rovshan Khan, Ejaz Ahmad Khatib, Mahalaqua Nazli Kosen, Soewarta Koyanagi, Ai Kumar, G. Anil Landires, Ivan Lasrado, Savita Lim, Stephen S. Liu, Xuefeng Lobo, Stany W. Lugo, Alessandra Makki, Alaa Mendoza, Walter Mersha, Amanual Getnet Mihretie, Kebadnew Mulatu Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Noncommunicable Diseases World Health Organization (WHO) Geneva Switzerland Department of Parasitology and Mycology Jahrom University of Medical Sciences Jahrom Iran The Institute of Pharmaceutical Sciences (TIPS) Tehran University of Medical Sciences Tehran Iran School of Pharmacy Tehran University of Medical Sciences Tehran Iran Clinical Sciences Department University of Sharjah Sharjah United Arab Emirates Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Department of Biosciences COMSATS Institute of Information Technology Islamabad Pakistan Department of Computer Science and Engineering University of Kurdistan Hewler Erbil Iraq Department of Medical Physiology University of Gondar Gondar Ethiopia Mayo Evidence-based Practice Center Mayo Clinic Foundation for Medical Education and Research Rochester MN United States Imam Abdulrahman Bin Faisal University Dammam Saudi Arabia Health Information Management and Technology Department Dammam Saudi Arabia Geriatric and Long Term Care Department Hamad Medical Corporation Doha Qatar Rumailah Hospital Hamad Medical Corporation Doha Qatar Department of Biological Sciences National University of Medical Sciences (NUMS) Rawalpindi Pakistan Health Management and Economics Research Center Tehran Iran Department of Community Medicine King Abdulaziz University Jeddah Saudi Arabia Department of Population and Behavioural Sciences University of Health and Allied Sciences Ho Ghana Social Determinants of Health Research Center Birjand University of Medical Sciences Birjand Iran Department of Maternal and Child Health Sultan Qaboos University Muscat Oman Department of Health System and Health Economics Bahir Dar University Bahir Dar Ethiopia Department of Pharmacy University of Huddersfield Huddersfield United Kingdom Unit of Biochemistry Universiti

Background: Hearing loss affects access to spoken language, which can affect cognition and development, and can negatively affect social wellbeing. We present updated estimates from the Global Burden of Disease (GBD) study on the prevalence of hearing loss in 2019, as well as the condition's associated disability. Methods: We did systematic reviews of population-representative surveys on hearing loss prevalence from 1990 to 2019. We fitted nested meta-regression models for severity-specific prevalence, accounting for hearing aid coverage, cause, and the presence of tinnitus. We also forecasted the prevalence of hearing loss until 2050. Findings: An estimated 1·57 billion (95% uncertainty interval 1·51–1·64) people globally had hearing loss in 2019, accounting for one in five people (20·3% [19·5–21·1]). Of these, 403·3 million (357·3–449·5) people had hearing loss that was moderate or higher in severity after adjusting for hearing aid use, and 430·4 million (381·7–479·6) without adjustment. The largest number of people with moderate-to-complete hearing loss resided in the Western Pacific region (127·1 million people [112·3–142·6]). Of all people with a hearing impairment, 62·1% (60·2–63·9) were older than 50 years. The Healthcare Access and Quality (HAQ) Index explained 65·8% of the variation in national age-standardised rates of years lived with disability, because countries with a low HAQ Index had higher rates of years lived with disability. By 2050, a projected 2·45 billion (2·35–2·56) people will have hearing loss, a 56·1% (47·3–65·2) increase from 2019, despite stable age-standardised prevalence. Interpretation: As populations age, the number of people with hearing loss will increase. Interventions such as childhood screening, hearing aids, effective management of otitis media and meningitis, and cochlear implants have the potential to ameliorate this burden. Because the burden of moderate-to-complete hearing loss is concentrated in countries with low health-ca

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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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