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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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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

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NATURE GENETICS 2018年第5期50卷 765-766页

作者： Turcot, Valerie Lu, Yingchang Highland, Heather M. Schurmann, Claudia Justice, Anne E. Fine, Rebecca S. Bradfield, Jonathan P. Esko, Tonu Giri, Ayush Graff, Mariaelisa Guo, Xiuqing Hendricks, Audrey E. Karaderi, Tugce Lempradl, Adelheid Locke, Adam E. Mahajan, Anubha Marouli, Eirini Sivapalaratnam, Suthesh Young, Kristin L. Alfred, Tamuno Feitosa, Mary F. Masca, Nicholas G. D. Manning, Alisa K. Medina-Gomez, Carolina Mudgal, Poorva Ng, Maggie C. Y. Reiner, Alex P. Vedantam, Sailaja Willems, Sara M. Winkler, Thomas W. Abecasis, Goncalo Aben, Katja K. Alam, Dewan S. Alharthi, Sameer E. Allison, Matthew Amouyel, Philippe Asselbergs, Folkert W. Auer, Paul L. Balkau, Beverley Bang, Lia E. Barroso, Ines Bastarache, Lisa Benn, Marianne Bergmann, Sven Bielak, Lawrence F. Bluher, Matthias Boehnke, Michael Boeing, Heiner Boerwinkle, Eric Boger, Carsten A. Bork-Jensen, Jette Bots, Michiel L. Bottinger, Erwin P. Bowden, Donald W. Brandslund, Ivan Breen, Gerome Brilliant, Murray H. Broer, Linda Brumat, Marco Burt, Amber A. Butterworth, Adam S. Campbell, Peter T. Cappellani, Stefania Carey, David J. Catamo, Eulalia Caulfield, Mark J. Chambers, John C. Chasman, Daniel I. Chen, Yii-Der I. Chowdhury, Rajiv Christensen, Cramer Chu, Audrey Y. Cocca, Massimiliano Collins, Francis S. Cook, James P. Corley, Janie Galbany, Jordi Corominas Cox, Amanda J. Crosslin, David S. Cuellar-Partida, Gabriel D'Eustacchio, Angela Danesh, John Davies, Gail Bakker, Paul I. W. Groot, Mark C. H. Mutsert, Renee Deary, Ian J. Dedoussis, George Demerath, Ellen W. Heijer, Martin Hollander, Anneke I. Ruijter, Hester M. Dennis, Joe G. Denny, Josh C. Angelantonio, Emanuele Drenos, Fotios Du, Mengmeng Dube, Marie-Pierre Dunning, Alison M. Easton, Douglas F. Edwards, Todd L. Ellinghaus, David Ellinor, Patrick T. Elliott, Paul Evangelou, Evangelos Farmaki, Aliki-Eleni Farooqi, I. Sadaf Faul, Jessica D. Fauser, Sascha Feng, Shuang Ferrannini, Ele Ferrieres, Jean Florez, Jose C. Ford, Ian Fornage, Myriam Franco, Oscar H. Franke, Andre Franks, Paul W. Friedrich, Ne Montreal Heart Institute Université de Montréal Montreal Quebec Canada Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University School of Medicine Nashville TN USA Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York NY USA Genetics of Obesity and Related Metabolic Traits Program Icahn School of Medicine at Mount Sinai New York NY USA Department of Epidemiology University of North Carolina Chapel Hill NC USA Human Genetics Center University of Texas School of Public Health University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences University of Texas Health Science Center at Houston Houston TX USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Genetics Harvard Medical School Boston MA USA Division of Endocrinology and Center for Basic and Translational Obesity Research Boston Children’s Hospital Boston MA USA Center for Applied Genomics Division of Human Genetics Children’s Hospital of Philadelphia Philadelphia PA USA Quantinuum Research LLC San Diego CA USA Estonian Genome Center University of Tartu Tartu Estonia Division of Epidemiology Department of Medicine Institute for Medicine and Public Health Vanderbilt Genetics Institute Vanderbilt University Nashville TN USA Institute for Translational Genomics and Population Sciences LABioMed at Harbor-UCLA Medical Center Torrance CA USA Wellcome Trust Sanger Institute Hinxton UK Department of Mathematical and Statistical Sciences University of Colorado Denver CO USA Wellcome Trust Centre for Human Genetics University of Oxford Oxford UK Department of Biological Sciences Faculty of Arts and Sciences Eastern Mediterranean University Famagusta Cyprus Max Planck Institute of Immunobiology and Epigenetics Freiburg Germany Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (***35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

关键词： Genome-wide association studies Obesity

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Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways

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Chemico-Biological Interactions 2023年第1期370卷 110329页

作者： Hsu, Chia-Hung Weng, Pei-Wei Chen, Ming-Yao Yeh, Chi-Tai Setiawan, Syahru Agung Yadav, Vijesh Kumar Wu, Alexander T.H. Tzeng, David T.W. Gong, Jian-Xian Yang, Zhen Tzeng, Yew-Min Department of Emergency Medicine Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei City 11031 Taiwan Department of Emergency Medicine School of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Shuang Ho Hospital New Taipei City 23561 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Ph.D. Program of Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan School of Life Sciences The Chinese University of Hong Kong 999077 Hong Kong Lifebit London EC2A 2AP United Kingdom Laboratory of Chemical Genomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen 518055 China State Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China Shenzhen Bay Laboratory Shenzhen 518055 China Department of Applied Science National Taitung University Taitung

Until recently, sorafenib has been the only treatment approved by the U.S. Food and Drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers CD133, KLF4, CD44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p < 0.001) and tumorsphere formation (p < 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment. © 2022 Elsevier B.V.

关键词： Antrocinol Cancer stemness Hepatocellular carcinoma KRAS/AKT/ERK axis Sorafenib

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Experimental and analytical pipeline for sub-genomic RNA landscape of coronavirus by Nanopore sequencer

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Microbiology spectrum 2024年第4期12卷 e0395423页

作者： Bo-Jia Chen Ching-Hung Lin Hung-Yi Wu James J Cai Day-Yu Chao Doctoral Program in Microbial Genomics National Chung Hsing University and Academia Sinica Taichung Taiwan. Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University Taichung Taiwan. Department of Veterinary Integrative Biosciences Texas A&M University College Station Texas USA. Graduate Institute of Microbiology and Public Health College of Veterinary Medicine National Chung Hsing University Taichung Taiwan. Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan.

Coronaviruses (CoVs), including severe acute respiratory syndrome coronavirus 2, can infect a variety of mammalian and avian hosts with significant medical and economic consequences. During the life cycle of CoV, a coordinated series of subgenomic RNAs, including canonical subgenomic messenger RNA and non-canonical defective viral genomes (DVGs), are generated with different biological implications. Studies that adopted the Nanopore sequencer (ONT) to investigate the landscape and dynamics of viral RNA subgenomic transcriptomes applied arbitrary bioinformatics parameters without justification or experimental validation. The current study used bovine coronavirus (BCoV), which can be performed under biosafety level 2 for library construction and experimental validation using traditional colony polymerase chain reaction and Sanger sequencing. Four different ONT protocols, including RNA direct and cDNA direct sequencing with or without exonuclease treatment, were used to generate RNA transcriptomic libraries from BCoV-infected cell lysates. Through rigorously examining the k-mer, gap size, segment size, and bin size, the optimal cutoffs for the bioinformatic pipeline were determined to remove the sequence noise while keeping the informative DVG reads. The sensitivity and specificity of identifying DVG reads using the proposed pipeline can reach 82.6% and 99.6% under the k-mer size cutoff of 15. Exonuclease treatment reduced the abundance of RNA transcripts; however, it was not necessary for future library preparation. Additional recovery of clipped BCoV nucleotide sequences with experimental validation expands the landscape of the CoV discontinuous RNA transcriptome, whose biological function requires future investigation. The results of this study provide the benchmarks for library construction and bioinformatic parameters for studying the discontinuous CoV RNA *** defective viral genomic RNA, containing all the -acting elements required

关键词： Nanopore sequencer bovine coronavirus discontinuous RNA

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B-252 In Vitro Expression Analysis of Variants in the Upstream Region of Genes Related to Familial Hypercholesterolemia

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Clinical Chemistry 2023年第SUPPLEMENT_1期69卷

作者： de Araujo, J G Tamborlin, L Luchessi, A D Hirata, R D Hirata, M H Silbiger, V N Northeast Biotechnology Network (RENORBIO) Graduate Program in Biotechnology Federal University of Rio Grande do Norte Natal Brazil Institute of Biosciences São Paulo State University (UNESP) Rio Claro Brazil Laboratory of Biotechnology School of Applied Sciences University of Campinas Limeira Brazil Department of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil

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Impact of biologics initiation on oral corticosteroid use in the International Severe Asthma Registry and the Optimum Patient Care Research Database: a pooled analysis of real-world data

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The journal of allergy and clinical immunology. In practice 2025年

作者： Wenjia Chen Trung N Tran John Townend George C Christoff Ming-Ju Tsai Alan Altraja Belinda Cochrane Borja G Cosio Martin Sivori Ruth B Murray Michael P Makris Ghislaine Scelo Lakmini Bulathsinhala Ledit R F Ardusso María Eugenia Franchi Jorge Máspero Fernando Saldarini Ana María Stok Ana Giselle Tomaszuk Anahí Yañez Benjamin Emmanuel Cathy Emmas Konstantinos Kostikas Andrew N Menzies-Gow Neda Stjepanovic Sinthia Z Bosnic-Anticevich Eve Denton Peter G Gibson Mark Hew Christine Jenkins Peter G Middleton Matthew J Peters John W Upham Guy G Brusselle Renaud Louis Florence Schleich Paulo Márcio Pitrez Todor A Popov Celine Bergeron Mohit Bhutani Kenneth R Chapman Andréanne Côté Simon Couillard Delbert R Dorscheid M Diane Lougheed Mohsen Sadatsafavi Carlos Andrés Celis-Preciado Libardo Jiménez-Maldonado Bellanid Rodríguez-Cáceres Diana Jimena Cano Rosales Ivan Solarte Carlos A Torres-Duque Susanne Hansen Celeste M Porsbjerg Charlotte Suppli Ulrik Arnaud Bourdin Petros Bakakos Konstantinos P Exarchos Athena Gogali Aggelos A Ladias Nikolaos G Papadopoulos Andriana I Papaioannou Richard W Costello Breda Cushen Patrick D Mitchell Giorgio Walter Canonica Enrico Heffler Francesca Puggioni Takashi Iwanaga Tatsuya Nagano Yuji Tohda Mona S Al-Ahmad Désirée Larenas- Linnemann Bernt Bøgvald Aarli Sverre Lehmann Piotr Kuna José Alberto Ferreira João A Fonseca Cláudia Chaves Loureiro Riyad Al-Lehebi Adeeb A Bulkhi Yah Ru Juang Mariko Siyue Koh Anqi Liu Chin Kook Rhee Luis Perez-de-Llano Pin-Kuei Fu Diahn-Warng Perng Chau-Chyun Sheu Hao-Chien Wang Bassam Mahboub Laila Salameh John Busby Liam G Heaney David J Jackson Pujan H Patel Paul E Pfeffer Flavia Hoyte Rohit K Katial Njira Lugogo Roy Alton Pleasants Eileen Wang Michael E Wechsler Aaron Beastall Victoria Carter Nevaashni Eleangovan Kirsty Fletton David B Price Saw Swee Hock School of Public Health National University of Singapore Singapore. BioPharmaceuticals Medical AstraZeneca Gaithersburg MD USA. Observational and Pragmatic Research Institute Singapore Singapore Optimum Patient Care Cambridge UK. Medical University Sofia Faculty of Public Health Bulgaria. Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Department of Internal Medicine School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan. Department of Pulmonology University of Tartu and Lung Clinic Tartu University Hospital Tartu Estonia. Department of Respiratory and Sleep Medicine Campbelltown Hospital (SWSLHD) Campbelltown New South Wales Australia School of Medicine Western Sydney University Sydney New South Wales Australia. Son Espases University Hospital-IdISBa (Institut d'Investigació Sanitària Illes Balears)-Ciberes Mallorca Spain. Neumonology Center of School of Medicine University of Buenos Aires Hospital "Dr.JM.Ramos Mejia" Buenos Aires Argentina. Allergy Unit National and Kapodistrian University of Athens University General Hospital 'Attikon' Greece. Pulmonology Allergy and Immunology Department Rosario School of Medicine National University of Rosario Rosario SF Argentina. Hospital Universitario Austral Buenos Aires Argentina. Clinical Research for Allergy and Respiratory Medicine CIDEA Foundation Buenos Aires Argentina University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine Buenos Aires Argentina. Section Pulmonology Hospital Santojanni Autonomous City of Buenos Aires Argentina. Investigaciones en Patologias Respiratorias San Miguel de Tucuman Tucuman Argentina. AAMR ( Asociación Argentina de Medicina Respiratoria) Buenos Aires Argentina. The Allergy and Respiratory Medicine Research Center- InAER - Buenos Aires Argentina. BioPhar

BACKGROUND:For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited. OBJECTIVE:To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in SA patients from real-world specialist and primary care settings. METHODS:From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, UK), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2). The impact of biologic initiation on TOCS (including bursts for exacerbations) daily dose in the first and second year follow-up period was estimated using multivariable generalized linear models. RESULTS:Among 5663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second year of follow-up were 2.38 (95% CI, 1.87-3.04) and 2.11 (95% CI, 1.65-2.70), whereas the ORs of low (0-5mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61) respectively. Compared to non-initiators, biologic initiators had a substantially higher chance of achieving >75% reduction from baseline (OR [95% CI]: 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second year, respectively). These findings remained persistent and robust, when analyses were repeated with one country setting removed at a time. CONCLUSION:Biologic initiation in SA patients led to substantial reduction in TOCS exposure, in particular in the first year. Future analyses will explore the impact on OCS-related adverse health events.

关键词： Severe asthma anti-IL4/13 anti-IL5 anti-IgE biologics difficult-to-treat asthma monoclonal antibody oral corticosteroids real-world evidence steroids

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Application of Emerging Innovations in Microbiome Science to Space Development and Settlement Systems 73

Application of Emerging Innovations in Microbiome Science to...

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73rd International Astronautical Congress, IAC 2022

作者： Nastasi, Nicholas Anderson, Matthew Z. Balasubrahmaniam, Neeraja Bope, Ashleigh Britt, Rodney D. Cochran, Samuel J. Gill, Samuel J. Hegarty, Bridget Lee, Jiyoung Stamps, Blake W. Stickney, Amanda Taylor, Christopher G. Tram, Nguyen K. Van Dusen, John Varaljay, Vanessa A. Weir, Mark H. Horack, John M. Oglesbee, Michael Sullivan, Matthew B. Dannemiller, Karen C. Department of Civil Environmental & Geodetic Engineering Ohio State University ColumbusOH United States Division of Environmental Health Sciences College of Public Health Ohio State University ColumbusOH United States Environmental Sciences Graduate Program Ohio State University ColumbusOH United States Department of Microbiology College of Arts and Sciences Ohio State University ColumbusOH United States Department of Microbial Infection and Immunity Ohio State University ColumbusOH United States Center for Perinatal Research The Abigail Wexner Research Institute Nationwide Children's Hospital Department of Pediatrics Ohio State University ColumbusOH United States Department of Civil and Environmental Engineering Case School of Engineering Case Western Reserve University ClevelandOH United States Department of Food Science and Technology Ohio State University ColumbusOH United States Infectious Diseases Institute Ohio State University ColumbusOH United States Soft Matter Materials Branch Materials and Manufacturing Directorate Air Force Research Laboratory Wright - Patterson AFBOH United States Department of Plant Pathology College of Food Agriculture and Environmental Science Ohio State University ColumbusOH United States Department of Anesthesiology & Pain Medicine Nationwide Children's Hospital ColumbusOH United States Airman Systems Directorate 711th Human Performance Wing Air Force Research Laboratory WPAFBOH United States Sustainability Institute Ohio State University ColumbusOH United States Department of Mechanical and Aerospace Engineering College of Engineering John Glenn College of Public Affairs Ohio State University ColumbusOH United States Department of Veterinary Biosciences College of Veterinary Medicine Ohio State University ColumbusOH United States Center of Microbiome Science Ohio State University ColumbusOH United States

Future human spaceflight beyond low-Earth orbit will bring substantial changes and new requirements to the development of fully sustainable, healthy indoor human environments across a range of gravitational, radiative, and thermal conditions. One key aspect is understanding (and potentially leveraging) microorganisms that must coexist with humans, plants, and animals in enclosed habitats (their microbiota or microbiomes). Modern, genome-resolved microbiome science provides an opportunity to better understand how we can utilize microbes to optimize space missions and protect human health and well-being long-term. Microorganisms will be critical to mission success due to their direct or indirect interactions with 1) humans, 2) other living systems (e.g., plant and animal life as a food source and for experimentation), and 3) the built environment. For example, the human gut microbiome is a complex community that has important implications for human health and performance that include mental health, nutrition intake, and immune system function. The health of plant microbiomes is also critical for sustainable, dependable, and nutritious food production. Humans, plants, and other living systems (e.g., animals used in experimentation) will also shed microbes into the built environment, which may impact human exposure, plant health, system integrity, and planetary protection from microbial contamination in both forward and reverse directions. Microbes from all three systems will interact, resulting in potentially important 'non-linear' system implications that must be understood for the overall long-term sustainability of hardware, crew, and other living systems. This paper discusses recent advances in technology that expand measurement capabilities to ultra-low-biomass samples and now allow for better understanding of microbial taxa, community structure and drivers, and functional capacity, which together will empower microbiome-optimized deep-space human exploration miss

关键词： Bacteria

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ABCB1 Regulates Immune Genes in Breast Cancer

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Breast cancer (Dove Medical Press) 2023年 15卷 801-811页

作者： Han-Kun Chen Yi-Ling Chen Chih-Yang Wang Wei-Pang Chung Jung-Hua Fang Ming-Derg Lai Hui-Ping Hsu Department of Surgery Chi Mei Medical Center Tainan Taiwan. Department of Health and Nutrition Chia Nan University of Pharmacy and Science Tainan Taiwan. PhD Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 70403 Taiwan. Center of Applied Nanomedicine National Cheng Kung University Tainan Taiwan. Laboratory Animal Center College of Medicine National Cheng Kung University Tainan Taiwan. Department of Biochemistry and Molecular Biology National Cheng Kung University Tainan Taiwan. Institute of Basic Medical Sciences College of Medicine National Cheng Kung University Tainan Taiwan. Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan.

Background:Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and immune genes in breast cancer has not been widely studied. Methods:Microarray and RNA sequencing data were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal and Gene Expression Omnibus database. A patient-derived xenograft (PDX) model of HER2 breast cancer was established to investigate the association between and immune genes in breast cancer. Results:Expression of increased in doxorubicin-selected MCF-7/ADR cells. High expression of mRNA is correlated with lymph-node metastasis and worse overall survival in patients with breast cancer. is positively correlated with , and . In the HER2 stage IIA breast cancer PDX model, both doxorubicin and paclitaxel suppressed growth of P2 tumors. IL6, CSF1, CSF3, and PTGS2 expression were suppressed by paclitaxel but not doxorubicin. Intrasplenic MDSCs, including CD11bLy6G and CD11bLy6C cells, were more abundant than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well controlled after paclitaxel-trastuzumab combined therapy. Conclusion:ABCB1 was a poor predictor of HER2 LN breast cancer. Regulation of immune genes by ABCB1 contributed to cancer recurrence and treatment effect. The PDX model was suitable for investigation the expression of target genes and expansion of immune cells.

关键词： ABC transporters ABCB1 breast cancer myeloid-derived suppressor cells patient-derived xenograft

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A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection (Oct, 10.1038/s41590-021-01030-z, 2021)

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NATURE IMMUNOLOGY 2022年第2期23卷 341-341页

作者： Andreakos, Evangelos Abel, Laurent Vinh, Donald C. Kaja, Elzbieta Drolet, Beth A. Zhang, Qian O'Farrelly, Cliona Novelli, Giuseppe Rodriguez-Gallego, Carlos Haerynck, Filomeen Prando, Carolina Pujol, Aurora Su, Helen C. Casanova, Jean-Laurent Spaan, Andras N. Laboratory of Immunobiology Center for Clinical Experimental Surgery and Translational Research Biomedical Research Foundation of the Academy of Athens Athens Greece St. Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France University of Paris Imagine Institute Paris France Department of Medicine Division of Infectious Diseases McGill University Health Centre Montréal Québec Canada Infectious Disease Susceptibility Program Research Institute McGill University Health Centre Montréal Québec Canada MNM Diagnostics Inc. Lewes DE USA Department of Dermatology School of Medicine and Public Health University of Wisconsin Madison WI USA Comparative Immunology Group School of Biochemistry and Immunology Trinity Biomedical Sciences Institute Trinity College Dublin Dublin Ireland Department of Biomedicine and Prevention University of Rome Tor Vergata Rome Italy Department of Immunology Hospital Universitario de Gran Canaria Dr. Negrín Canarian Health System Las Palmas de Gran Canaria Las Palmas Spain Department of Clinical Sciences University Fernando Pessoa Canarias Las Palmas de Gran Canaria Las Palmas Spain Department of Pediatric Immunology and Pulmonology Centre for Primary Immunodeficiency Ghent (CPIG) PID Research Laboratory Jeffrey Modell Diagnosis and Research Centre Ghent University Hospital Ghent Belgium Faculdades Pequeno Príncipe Instituto de Pesquisa Pelé Pequeno Príncipe Curitiba Brazil Neurometabolic Diseases Laboratory Bellvitge Biomedical Research Institute (IDIBELL) L’Hospitalet de Llobregat Barcelona Spain Catalan Institution of Research and Advanced Studies (ICREA) Barcelona Spain Center for Biomedical Research on Rare Diseases U759 (CIBERER) ISCIII Barcelona Spain Intramural Research Program National Institute of Allergy and Infectious Disease

SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.

关键词： Infection Viral infection Biomedicine general Immunology Infectious Diseases

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Overview of the Head and Neck Tumor Segmentation for Magnetic Resonance Guided Applications (HNTS-MRG) 2024 Challenge

arXiv

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arXiv 2024年

作者： Wahid, Kareem A. Dede, Cem El-Habashy, Dina M. Kamel, Serageldin Rooney, Michael K. Khamis, Yomna Abdelaal, Moamen R.A. Ahmed, Sara Corrigan, Kelsey L. Chang, Enoch Dudzinski, Stephanie O. Salzillo, Travis C. McDonald, Brigid A. Mulder, Samuel L. McCullum, Lucas Alakayleh, Qusai Sjogreen, Carlos He, Renjie Mohamed, Abdallah S.R. Lai, Stephen Y. Christodouleas, John P. Schaefer, Andrew J. Naser, Mohamed A. Fuller, Clifton D. Department of Radiation Oncology The University of Texas MD Anderson Cancer HoustonTX United States Department of Imaging Physics The University of Texas MD Anderson Cancer HoustonTX United States Transitional Year Program Corewell Health Wiliam Beaumont Royal OakMI United States Department of Radiation Oncology University of Maryland School of Medicine BaltimoreMD United States Department of Clinical Oncology and Nuclear Medicine Faculty of Medicine Alexandria University Alexandria Egypt UT MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences Houston United States Department of Radiation Oncology Baylor College of Medicine HoustonTX United States Department of Head and Neck Surgery The University of Texas MD Anderson Cancer HoustonTX United States Elekta AtlantaGA United States Department of Computational Applied Mathematics and Operations Research Rice University HoustonTX United States

Magnetic resonance (MR)-guided radiation therapy (RT) is enhancing head and neck cancer (HNC) treatment through superior soft tissue contrast and longitudinal imaging capabilities. However, manual tumor segmentation remains a significant challenge, spurring interest in artificial intelligence (AI)-driven automation. To accelerate innovation in this field, we present the Head and Neck Tumor Segmentation for MR-Guided Applications (HNTS-MRG) 2024 Challenge, a satellite event of the 27th International Conference on Medical Image Computing and Computer Assisted Intervention. This challenge addresses the scarcity of large, publicly available AI-ready adaptive RT datasets in HNC and explores the potential of incorporating multi-timepoint data to enhance RT auto-segmentation performance. Participants tackled two HNC segmentation tasks: automatic delineation of primary gross tumor volume (GTVp) and gross metastatic regional lymph nodes (GTVn) on pre-RT (Task 1) and mid-RT (Task 2) T2-weighted scans. The challenge provided 150 HNC cases for training and 50 for testing, hosted on *** using a Docker submission framework. In total, 19 independent teams from across the world qualified by submitting both their algorithms and corresponding papers, resulting in 18 submissions for Task 1 and 15 submissions for Task 2. Evaluation using the mean aggregated Dice Similarity Coefficient showed top-performing AI methods achieved scores of 0.825 in Task 1 and 0.733 in Task 2. These results surpassed clinician interobserver variability benchmarks, marking significant strides in automated tumor segmentation for MR-guided RT applications in HNC. © 2024, CC BY.

关键词： Magnetic resonance imaging

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