Author: "Yong Loo Lin School of Medicine, National University of Singapore" / Search Limiters: Available in Library Collection - Searchworks@Jio Institute Digital Library Search Results

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9,634 results on '"Yong Loo Lin School of Medicine, National University of Singapore"'

1. Telomere-mediated genomic instability and the clinico-pathological parameters in breast cancer

Author: Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore ; Michigan Center for Translation Pathology, University of Michigan Health System, Comprehensive Cancer Center, Ann Arbor, MI, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore, Department of Pathology, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore ; Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Poonepalli, Anuradha, Banerjee, Birendranath, Ramnarayanan, Kalpana, Palanisamy, Nallasivam, Putti, Thomas Choudary, Hande, M. Prakash, Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore ; Michigan Center for Translation Pathology, University of Michigan Health System, Comprehensive Cancer Center, Ann Arbor, MI, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore, Department of Pathology, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore ; Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Poonepalli, Anuradha, Banerjee, Birendranath, Ramnarayanan, Kalpana, Palanisamy, Nallasivam, Putti, Thomas Choudary, and Hande, M. Prakash
Abstract: A study was undertaken to correlate telomere dysfunction and genomic instability with the histopathological grades and the estrogen and progesterone receptor status in breast cancer. Sixty-one archived breast tissues (38 cancer tissues and 23 paired normal tissues) were used in the study. The breast tumor tissues showed significantly shorter telomeres (7.7 kb) compared with the paired adjacent tissues (9.0 kb) by Southern blot analysis. Moreover, telomere shortening was more significant in Grade III tumors than in the Grade II tumors ( P = 0.05). Quantitative fluorescence in situ hybridization on paraffin tissue sections revealed a similar trend in telomere shortening. Telomere attrition was associated with telomere dysfunction as revealed by the presence of significantly higher anaphase bridges in tumor cells which was tumor grade dependent. Furthermore, estrogen receptive negative tumors displayed higher anaphase and internuclear bridges. Selected samples from each grade showed greater genomic imbalances in the higher grades than the lower grade tumors as detected by array-comparative genomic hybridization. Telomerase activity was found to be higher in the higher grades (Grade II and III) compared with the lower grade (Grade I). The average mRNA expression of TRF1 and POT1 was lower in the tumor tissues than in the normal tissues. Tankyrase 1 mRNA expression showed a grade-dependent increase in tumor tissues and its expression was also high in estrogen and progesterone negative tumors. The data support the notion that telomere dysfunction might be of value as a marker of aggressiveness of the tumors in breast cancer patients. ?? 2008 Wiley-Liss, Inc.
Published: 2008

2. Studying Phenotypes of Gestational Diabetes Mellitus in an Asian Pregnant Cohort (GDM-CARE)

Author: Lingjun Li, Assistant Director, Public Affairs, Global Centre for Asian Women's Health, Assistant Professor, Department of O&G, Yong Loo Lin School of Medicine, National University of Singapore
Published: 2024

3. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology ; Biochemistry and Molecular Biology, Dpt. of Cancer & Cell Biology ; University of Cincinnati, Institut Jacques Monod (IJM) ; CNRS - Université Paris VII - Paris Diderot, Virologie humaine ; INSERM - IFR128 - École Normale Supérieure (ENS) - Lyon, Instituto de Investigaciones Biotecnológicas, (IIB-INTECH) ; Universidad Nacional de San Martin, MRC Centre for Developmental Neurobiology ; MRC Centre for Developmental Neurobiology, University of Brescia ; University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; Hanson Institute, Adelaide, Jeune Equipe JE 2526 ; Université d'Auvergne - Clermont-Ferrand I, Institut de Recherche Agronomique (Unité sous contrat USC-2018) ; Institut national de la recherche agronomique (INRA), Facultad de Medicina ; Universidad de Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, 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Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Cong-Zhao, Zhu, Changlian, Zhu, Wei-Guo, Zhu, Xiao-Feng, Zhu, Xiongwei, Zhu, Yuangang, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, Zschocke, Jürgen, Zuckerbraun, Brian, Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la 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Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale 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Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, 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Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, Schapira, Anthony H V, Scharl, Michael, Schätzl, Hermann M, Scheper, Wiep, Schiaffino, Stefano, Schneider, Claudio, Schneider, Marion E, Schneider-Stock, Regine, Schoenlein, Patricia V, Schorderet, Daniel F, Schüller, Christoph, Schwartz, Gary K, Scorrano, Luca, Sealy, Linda, Seglen, Per O, Segura-Aguilar, Juan, Seiliez, Iban, Seleverstov, Oleksandr, Sell, Christian, Seo, Jong Bok, Separovic, Duska, Setaluri, Vijayasaradhi, Setoguchi, Takao, Settembre, Carmine, Shacka, John J, Shanmugam, Mala, Shapiro, Irving M, Shaulian, Eitan, Shaw, Reuben J, Shelhamer, James H, Shen, Han-Ming, Shen, Wei-Chiang, Sheng, Zu-Hang, Shi, Yang, Shibuya, Kenichi, Shidoji, Yoshihiro, Shieh, Jeng-Jer, Shih, Chwen-Ming, Shimada, Yohta, Shimizu, Shigeomi, Shintani, Takahiro, Shirihai, Orian S, Shore, Gordon C, Sibirny, Andriy A, Sidhu, Stan B, Sikorska, Beata, Silva-Zacarin, Elaine C M, Simmons, Alison, Simon, Anna Katharina, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, Sinclair, David A, Singh, Rajat, Sinha, Debasish, Sinicrope, Frank A, Sirko, Agnieszka, Siu, Parco M, Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P, Slack, Ruth S, Smaili, Soraya S, Smith, Duncan R, Soengas, Maria S, Soldati, Thierry, Song, Xueqin, Sood, Anil K, Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Srinivasula, Srinivasa M, Stefanis, Leonidas, Steffan, Joan S, Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van Den Berghe, Greet, Van Der Klei, Ida J, Van Doorn, Wouter, Van Dyk, Linda F, Van Egmond, Marjolein, Van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, 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Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Cong-Zhao, Zhu, Changlian, Zhu, Wei-Guo, Zhu, Xiao-Feng, Zhu, Xiongwei, Zhu, Yuangang, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, Zschocke, Jürgen, and Zuckerbraun, Brian
Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

4. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology ; Biochemistry and Molecular Biology, Dpt. of Cancer & Cell Biology ; University of Cincinnati, Institut Jacques Monod (IJM) ; CNRS - Université Paris VII - Paris Diderot, Virologie humaine ; INSERM - IFR128 - École Normale Supérieure (ENS) - Lyon, Instituto de Investigaciones Biotecnológicas, (IIB-INTECH) ; Universidad Nacional de San Martin, MRC Centre for Developmental Neurobiology ; MRC Centre for Developmental Neurobiology, University of Brescia ; University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; Hanson Institute, Adelaide, Jeune Equipe JE 2526 ; Université d'Auvergne - Clermont-Ferrand I, Institut de Recherche Agronomique (Unité sous contrat USC-2018) ; Institut national de la recherche agronomique (INRA), Facultad de Medicina ; Universidad de Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, 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Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, Schapira, Anthony H V, Scharl, Michael, Schätzl, Hermann M, Scheper, Wiep, Schiaffino, Stefano, Schneider, Claudio, Schneider, Marion E, Schneider-Stock, Regine, Schoenlein, Patricia V, Schorderet, Daniel F, Schüller, Christoph, Schwartz, Gary K, Scorrano, Luca, Sealy, Linda, Seglen, Per O, Segura-Aguilar, Juan, Seiliez, Iban, Seleverstov, Oleksandr, Sell, Christian, Seo, Jong Bok, Separovic, Duska, Setaluri, Vijayasaradhi, Setoguchi, Takao, Settembre, Carmine, Shacka, John J, Shanmugam, Mala, Shapiro, Irving M, Shaulian, Eitan, Shaw, Reuben J, Shelhamer, James H, Shen, Han-Ming, Shen, Wei-Chiang, Sheng, Zu-Hang, Shi, Yang, Shibuya, Kenichi, Shidoji, Yoshihiro, Shieh, Jeng-Jer, Shih, Chwen-Ming, Shimada, Yohta, Shimizu, Shigeomi, Shintani, Takahiro, Shirihai, Orian S, Shore, Gordon C, Sibirny, Andriy A, Sidhu, Stan B, Sikorska, Beata, Silva-Zacarin, Elaine C M, Simmons, Alison, Simon, Anna Katharina, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, Sinclair, David A, Singh, Rajat, Sinha, Debasish, Sinicrope, Frank A, Sirko, Agnieszka, Siu, Parco M, Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P, Slack, Ruth S, Smaili, Soraya S, Smith, Duncan R, Soengas, Maria S, Soldati, Thierry, Song, Xueqin, Sood, Anil K, Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Srinivasula, Srinivasa M, Stefanis, Leonidas, Steffan, Joan S, Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

5. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; 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LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; 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biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, 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Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van Den Berghe, Greet, Van Der Klei, Ida J, Van Doorn, Wouter, Van Dyk, Linda F, Van Egmond, Marjolein, Van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, 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Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

6. Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Author: Ezequiel Ruiz-Mateos, Naomi Mc Govern, Bernett Lee, Tamas Fulop, Karolina Pilipow, Tze Pin Ng, Crystal Tze Ying Tan, Shu Wen Tan, Reena Rajasuriar, Hartmut Geiger, Wilson How, Mai Chan Lau, Benoit Malleret, Amanda Amoah, Florent Ginhoux, Marie Strickland, Jin Miao Chen, Maria Carolina Florian, Glenn Wong, Enrico Lugli, Adeeba Kamarulzaman, Marion Chevrier, Veronica Zanon, Hassen Kared, Anis Larbi, Josephine Lum, [Kared,H, Tan,SW, Lau,MC, Chevrier,M, Tan,C, How,W, Wong,G, Strickland,M, Malleret,B, Govern,NM, Lum,J, Chen,JM, Lee,B, Ginhoux,F, Larbi,A] Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Immunos Building, Biopolis, Republic of Singapore. [Strickland,M] Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. [Malleret,B, Larbi,A] Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. [Amoah,A, Florian,MC, Geiger,H] Institute of Molecular Medicine, University of Ulm, Ulm, Germany. [Pilipow,K, Zanon,V, Lugli,E] Humanitas Clinical and Research Center, Laboratory of Translational Immunology (LTI), Rozzano, Italy. [Geiger,H] Experimental Hematology and Cancer Biology, CCHMC, Cincinnati, OH, USA. [Ruiz-Mateos,E] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain. [Fulop.T, Larbi,A] Department of Medicine, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada. [Rajasuriar,R, Kamarulzaman,A] Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia. [Rajasuriar,R] The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia. [Rajasuriar,R, Kamarulzaman,A] Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ng,TP] Gerontology Research Programme and Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., The study is supported by a research grant from the Agency for Science, Technology and Research (No. 10-036), by the Singapore Immunology Network and by a Starting Grant from the European Research Council (ERC-StG-2014 PERSYST 640511 to E.L.). A.L. is a scholar of International Society for Advancement of Cytometry (ISAC). R.R. and A.K. are funded by the High Impact Research/Ministry of Higher Education Research Grant, Malaysia (HIR/ MOHE, H-20001-E000001) and the RU grant (UMRG RP029-14HTM). E.R-M was supported by Consejería de Salud y Bienestar Social of Junta de Andalucía through the Nicolás Monardes Program (C-0032/17) and Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Fondos Europeos para el Desarrollo Regional, FEDER, grants PI16/ 00684, PI19/01127, RETICS, Red de Investigación en SIDA (RD16/0025/0020)., Agency for Science, Technology and Research A*STAR (Singapore), Singapore Immunology Network, European Research Council, International Society for Advancement of Cytometry, Ministry of Higher Education (Malaysia), Junta de Andalucía, Instituto de Salud Carlos III, European Commission, and Red Española de Investigación en SIDA
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Aging, animal diseases, General Physics and Astronomy, HIV Infections, Signal transduction, Immunological memory, Memory T cells, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, 0302 clinical medicine, Organisms::Eukaryota::Animals [Medical Subject Headings], Cytotoxic T cell, Flow cytometry, lcsh:Science, Wnt Signaling Pathway, beta Catenin, Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction::Wnt Signaling Pathway [Medical Subject Headings], Multidisciplinary, Wnt signaling pathway, Catenins, Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins [Medical Subject Headings], 3. Good health, Cell biology, Intercellular Signaling Peptides and Proteins, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Stem cell, Naive T cell, Science, T cells, Context (language use), chemical and pharmacologic phenomena, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], Thymus Gland, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Immune system, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::beta Catenin [Medical Subject Headings], Antigen, Antigens, CD, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Aging [Medical Subject Headings], Anatomy::Tissues::Lymphoid Tissue::Thymus Gland [Medical Subject Headings], Cateninas, Animals, Humans, Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Antigens [Medical Subject Headings], Anatomy::Cells::Stem Cells::Hematopoietic Stem Cells::Lymphoid Progenitor Cells::Precursor Cells, T-Lymphoid [Medical Subject Headings], Vía de señalización wnt, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Precursor Cells, T-Lymphoid, Células T de memoria, Gene Expression Profiling, General Chemistry, biochemical phenomena, metabolism, and nutrition, 030104 developmental biology, Sistema inmunológico, Phenomena and Processes::Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic Memory [Medical Subject Headings], bacteria, lcsh:Q, Citometría de flujo, Immunologic Memory, 030215 immunology
Abstract: The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history., Aging is associated with immune attrition that may impact the effectiveness of the immune system to protect the host from pathogens. Here the authors show that immune aging is associated with alterations in the Wnt/β-catenin signaling and reduced stem cell memory T lymphocytes, hinting the Wnt/β-catenin pathway as a potential therapy target.
Published: 2020

7. A comparative study of disorders of gut–brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study

Author: Johann P. Hreinsson, Reuben K. M. Wong, Jan Tack, Peter Whorwell, Marc A. Benninga, Viola Andresen, Bruno Bonaz, Suck Chei Choi, Enrico S. Corazziari, Javier Santos, Shin Fukudo, Motoyori Kanazawa, Xuicai Fang, Shrikant I. Bangdiwala, Ami D. Sperber, Olafur S. Palsson, Magnus Simrén, Institut Català de la Salut, [Hreinsson JP] Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [Wong RKM] Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. [Tack J] Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium. [Whorwell P] University of Manchester, Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK. [Benninga MA] Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands. [Andresen V] Department of Medicine, Israelitic Hospital, Hamburg, Germany. [Santos J] Laboratori de Fisiologia i Fisiopatologia Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Aparell Digestiu, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus, Pediatrics, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and ARD - Amsterdam Reproduction and Development
Subjects: Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], IRRITABLE-BOWEL-SYNDROME, Physiology, Clinical Neurology, QUESTIONNAIRE, cross-sectional studies, Qüestionaris, Nervous System::Central Nervous System::Brain [ANATOMY], Aparell digestiu - Malalties - Epidemiologia, sistema nervioso::sistema nervioso central::encéfalo::prosencéfalo::telencéfalo::cerebro [ANATOMÍA], CRITERIA, functional gastrointestinal disorders, Cervell, SCALE, irritable bowel syndrome, Science & Technology, Gastroenterology & Hepatology, Còlon irritable - Epidemiologia, Endocrine and Autonomic Systems, enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable [ENFERMEDADES], Neurosciences, Gastroenterology, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], functional constipation, functional dyspepsia, PREVALENCE, SEVERITY, Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome [DISEASES], RISK-FACTORS, Neurosciences & Neurology, Life Sciences & Biomedicine
Abstract: Functional constipation; Functional dyspepsia; Functional gastrointestinal disorders Estreñimiento funcional; Dispepsia funcional; Trastornos gastrointestinales funcionales Restrenyiment funcional; Dispèpsia funcional; Trastorns gastrointestinals funcionals Objective Many studies have been published on disorders of the gut–brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. Methods We used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. Results The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08–1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48–1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. Conclusion The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.
Published: 2023
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8. Biology of resident tissue macrophages

Author: Florent Ginhoux, Christopher Lee, School of Biological Sciences, Singapore Immunology Network, Yong Loo Lin School of Medicine, National University of Singapore, and Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre
Subjects: Macrophage, Macrophages, Biological sciences [Science], Cell Differentiation, Kupffer Cell, Microglia, Biology, Molecular Biology, Monocytes, Developmental Biology
Abstract: Although best known for their phagocytic and immunological functions, macrophages have increasingly been recognised as key players in the development, homeostasis and regeneration of their host tissues. Early during development, macrophages infiltrate and colonise all tissues within the body, developing symbiotically with their host tissues and acquiring unique functional adaptations based on the tissue microenvironment. These embryonic resident tissue macrophages (RTMs) are ontogenically distinct from the later adult bone marrow-derived monocytes, and in some tissues are self-maintained independently of general circulation at a steady state. In this article, we briefly discuss the ontogeny, maintenance and unique tissue adaptions of RTMs focusing on microglia, Kupffer cells, Langerhans cells, intestinal macrophages, cardiac macrophages and tumour-associated macrophages, and highlight their role in development, homeostasis and dysfunction. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) F.G. is supported by Singapore Immunology Network (SIgN) core funding. F.G. is a European Molecular Biology Organization (EMBO) YIP awardee and is supported by the National Research Foundation Singapore Senior Investigatorship (NRFI) (NRF2016NRF-NRFI001-02). C.Z.W.L. is supported by the Agency for Science, Technology and Research (A*STAR) Graduate Scholarship.
Published: 2022
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9. Insights into the evolution of regulated actin dynamics via characterization of primitive gelsolin/cofilin proteins from Asgard archaea

Author: Edward Manser, Robert Robinson, Linh T. Tran, Yohendran Baskaran, Laurent Blanchoin, Magali Orhant-Prioux, Caner Akıl, Agency for science, technology and research [Singapore] (A*STAR), Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Research Institute for Interdisciplinary Science, Okayama University, CytoMorphoLab, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Vidyasirimedhi Institute of Science and Technology, Agency for Science, Technology and Research, Singapore National Medical Research Council (NMRC Grant OFIRG/0067/2018), Vidyasirimedhi Institute of Science and Technology, Research Institute for Interdisciplinary Science, Japan Society for the Promotion of Science (KAKENHI Grant JP20H00476), European Project: 741773,AAA, Department of Pharmacology, Yong Loo Lin School of Medicine [Singapour], National University of Singapore (NUS), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), and Vidyasirimedhi Institute of Science and Technology [Thaïlande] (VISTEC)
Subjects: Protein Conformation, alpha-Helical, gelsolin, Archaeal Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, macromolecular substances, Biochemistry, Polymerization, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Genome, Archaeal, Lokiarchaeota, Amino Acid Sequence, Cytoskeleton, Actin, X-ray crystallography, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Chemistry, Actin filament severing, Biological Sciences, eukaryogenesis, Cofilin, musculoskeletal system, Actin cytoskeleton, Archaea, Actins, Cell biology, Actin Depolymerizing Factors, Asgard archaea, Profilin, biology.protein, Sequence Alignment, actin, Filopodia, Gelsolin, 030217 neurology & neurosurgery
Abstract: Significance Eukaryotic gelsolin superfamily proteins generally comprise three or more related domains. Here we characterize single- and double-domain gelsolins from Thorarchaeota (Thor). Similar domain architectures are present in Heimdall-, Loki-, and Odinarchaeota. Thor gelsolins are functional in regulating rabbit actin in in vitro assays, showing a range of activities including actin filament severing and bundling. These gelsolins bind to the eukaryotic gelsolin/cofilin-binding site on actin. Two-domain, but not one-domain, gelsolins are calcium regulated. Thor gelsolins appear to have the characteristics and structure consistent with primitive gelsolins/cofilins, suggesting that these single- and double-domain gelsolins are a record of a nascent preeukaryotic actin-regulation machinery., Asgard archaea genomes contain potential eukaryotic-like genes that provide intriguing insight for the evolution of eukaryotes. The eukaryotic actin polymerization/depolymerization cycle is critical for providing force and structure in many processes, including membrane remodeling. In general, Asgard genomes encode two classes of actin-regulating proteins from sequence analysis, profilins and gelsolins. Asgard profilins were demonstrated to regulate actin filament nucleation. Here, we identify actin filament severing, capping, annealing and bundling, and monomer sequestration activities by gelsolin proteins from Thorarchaeota (Thor), which complete a eukaryotic-like actin depolymerization cycle, and indicate complex actin cytoskeleton regulation in Asgard organisms. Thor gelsolins have homologs in other Asgard archaea and comprise one or two copies of the prototypical gelsolin domain. This appears to be a record of an initial preeukaryotic gene duplication event, since eukaryotic gelsolins are generally comprise three to six domains. X-ray structures of these proteins in complex with mammalian actin revealed similar interactions to the first domain of human gelsolin or cofilin with actin. Asgard two-domain, but not one-domain, gelsolins contain calcium-binding sites, which is manifested in calcium-controlled activities. Expression of two-domain gelsolins in mammalian cells enhanced actin filament disassembly on ionomycin-triggered calcium release. This functional demonstration, at the cellular level, provides evidence for a calcium-controlled Asgard actin cytoskeleton, indicating that the calcium-regulated actin cytoskeleton predates eukaryotes. In eukaryotes, dynamic bundled actin filaments are responsible for shaping filopodia and microvilli. By correlation, we hypothesize that the formation of the protrusions observed from Lokiarchaeota cell bodies may involve the gelsolin-regulated actin structures.
Published: 2020
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10. Seroprevalence of IgG antibodies against diphtheria antitoxin among migrant workers in Singapore, 2016–2019

Author: Li Wei Ang, Qi Gao, Lin Cui, Aysha Farwin, Matthias Paul Han Sim Toh, Irving Charles Boudville, Mark I-Cheng Chen, Angela Chow, Raymond Tzer-Pin Lin, Vernon Jian Ming Lee, Yee Sin Leo, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Saw Swee Hock School of Public Health, National University of Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Subjects: Adult, Transients and Migrants, Singapore, Basic protection, Diphtheria Toxoid, Research, Public Health, Environmental and Occupational Health, Immunity, Seroprevalence, Diphtheria, Migrant workers, complex mixtures, Antibodies, Bacterial, Diphtheria Antitoxin, Seroepidemiologic Studies, Immunoglobulin G, Humans, Medicine [Science], Public aspects of medicine, RA1-1270, geographic locations, Vaccination coverage
Abstract: Background: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks. Published version MICC was supported by the Ministry of Health, Singapore, under the Communicable Diseases – Public Health Research Grant (grant number MOHCS‑ 15MAR001) for sample collection. Laboratory testing for the seroprevalence of diphtheria among migrant workers was supported by the National Public Health Laboratory.
Published: 2022

11. Prevalence of measles antibodies among migrant workers in Singapore: a serological study to identify susceptible population subgroups

Author: Li Wei Ang, Qi Gao, Lin Cui, Aysha Farwin, Matthias Paul Han Sim Toh, Irving Charles Boudville, Mark I-Cheng Chen, Angela Chow, Raymond Tzer-Pin Lin, Vernon Jian Ming Lee, Yee Sin Leo, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Saw Swee Hock School of Public Health, National University of Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: Male, Transients and Migrants, Singapore, Research, Immunity, Infectious and parasitic diseases, RC109-216, Middle Aged, Antibodies, Viral, Migrant workers, Infectious Diseases, Seroepidemiologic Studies, Prevalence, Humans, Female, Medicine [Science], Vaccination coverage, Measles
Abstract: Background: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore. Methods: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT). Results: A total of 2234 migrant workers aged 20–49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2–91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965–1989 than those born in 1990–1999 (95.3% vs. 86.6%, p < 0.0005), whereas there was no significant difference by gender (90.8% in men vs. 89.9% in women, p = 0.508). 195 out of 213 samples with equivocal or negative ELISA results were tested positive using PRNT. Conclusion: The IgG seroprevalence in migrant workers was below the herd immunity threshold of 95% for measles. Sporadic outbreaks may occur in susceptible individuals due to high transmissibility of measles virus. Seroprevalence surveys can help identify susceptible subgroups for vaccination. Ministry of Health (MOH) Published version Sample collection was supported by the Ministry of Health, Singapore, under the Communicable Diseases—Public Health Research Grant (Grant Number MOHCS15MAR001). Laboratory testing for the seroprevalence of measles in migrant workers was supported by the National Public Health Laboratory.
Published: 2022

12. MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites

Author: Melissa Fullwood, KAIJING CHEN, Yi Xiang See, School of Biological Sciences, Cancer Science Institute of Singapore, National University of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, and Institute of Molecular and Cell Biology, A*STAR
Subjects: Biological sciences::Molecular biology [Science], Chromatin Interactions, Genetics, Biological sciences::Genetics [Science], Genetics (clinical), Cancer
Abstract: The MYC oncogene encodes for the MYC protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. MYC overexpression leads to MYC binding at active enhancers, resulting in a global transcriptional amplification of active genes. Since superenhancers are frequently dysregulated in cancer, we hypothesized that MYC preferentially invades into superenhancers and alters the cancer genome organization. To that end, we performed ChIP-seq, RNA-seq, 4C-seq and SIQHiC (Spike-in Quantitative Hi-C) on the U2OS osteosarcoma cell line with tetracycline-inducible MYC. MYC overexpression in U2OS cells modulated histone acetylation and increased MYC binding at superenhancers. SIQHiC analysis revealed increased global chromatin contact frequency, particularly at chromatin interactions connecting MYC binding sites at promoters and enhancers. Immunofluorescence staining showed that MYC molecules formed punctate foci at these transcriptionally active domains after MYC overexpression. These results demonstrate the accumulation of overexpressed MYC at promoter-enhancer hubs and suggest that MYC invades into enhancers through spatial proximity. At the same time, the increased protein-protein interactions may strengthen these chromatin interactions to increase chromatin contact frequency. CTCF siRNA knockdown in MYC overexpressed U2OS cells demonstrated that removal of architectural proteins can disperse MYC and abrogate the increase in chromatin contacts. By elucidating the chromatin landscape of MYC driven cancers, we can potentially target MYC associated chromatin interactions for cancer therapy. Ministry of Education (MOE) Accepted version This research is supported by the RNA Biology Center at the Cancer Science Institute of Singapore, NUS, as part of funding under the Singapore Ministry of Education Academic Research Fund Tier 3 grant awarded to Daniel Tenen (MOE2014-T3-1-006). This research is supported by the NRF Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative and a Singapore Ministry of Education Academic Research Fund Tier 2 grant awarded to M.J.F. (MOET2EP30120-0009).
Published: 2022

13. Osteomyelitis in Immunocompromised children and neonates, a case series

Author: Bryan Foong, Kenneth Pak Leung Wong, Carolin Joseph Jeyanthi, Jiahui Li, Kevin Boon Leong Lim, Natalie Woon Hui Tan, Lee Kong Chian School of Medicine (LKCMedicine), Yong Loo Lin School of Medicine, National University of Singapore, Duke-National University of Singapore Medical School, and KK Women’s and Children’s Hospital
Subjects: Male, Infant, Newborn, Immunocompromised children, Neonates, Osteomyelitis, Mycobacterium tuberculosis, Pediatrics, Mycobacterium bovis, RJ1-570, Anti-Bacterial Agents, Pediatrics, Perinatology and Child Health, Immunocompromised Children, Humans, Medicine [Science], Child, Research Article, Retrospective Studies
Abstract: Background Osteomyelitis in immunocompromised children can present differently from immunocompetent children and can cause devastating sequelae if treated inadequately. We aim to review the aetiology, clinical profile, treatment and outcomes of immunocompromised children with osteomyelitis. Methods Retrospective review of all immunocompromised children aged Results Fourteen patients were identified. There were 10 boys (71%), and the median age at admission was 70.5 months (inter-quartile range: 12.3–135.0 months). Causal organisms included, two were Staphylococcus aureus, two were Mycobacterium bovis (BCG), and one each was Mycobacterium tuberculosis, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia pseudomallei and Rhizopus sp. One patient had both Clostridium tertium and Clostridium difficile isolated. Treatment involved appropriate antimicrobials for a duration ranging from 6 weeks to 1 year, and surgery in 11 patients (79%). Wherever possible, the patients received treatment for their underlying immunodeficiency. For outcomes, only three patients (21%) recovered completely. Five patients (36%) had poor bone growth, one patient had recurrent discharge from the bone and one patient had palliative care for underlying osteosarcoma. Conclusions Although uncommon, osteomyelitis in immunocompromised children and neonates can be caused by unusual pathogens, and can occur with devastating effects. Treatment involves prolonged administration of antibiotics and surgery. Immune recovery also seems to be an important factor in bone healing.
Published: 2021

14. Serotype distribution and incidence of invasive early onset and late onset group B streptococcal disease amongst infants in Singapore

Author: Kai-Qian Kam, Koh Cheng Thoon, Wen Sim Nancy Tee, Michelle Lay Teng Ang, Natalie Woon Hui Tan, Kee Thai Yeo, Jiahui Li, Chia Yin Chong, Lee Kong Chian School of Medicine (LKCMedicine), KK Women’s and Children’s Hospital, Yong Loo Lin School of Medicine, National University of Singapore, and Duke-National University of Singapore Medical School
Subjects: Group B Streptococcus, Singapore, Group B streptococcus, Incidence, Infant, Infectious and parasitic diseases, RC109-216, GBS, Serogroup, Late Onset Disorders, Streptococcus agalactiae, Serotype, Infectious Diseases, Risk factors, Streptococcal Infections, EOD, Humans, Medicine [Science], LOD, Retrospective Studies, Research Article
Abstract: Background The current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD. Methods A retrospective study of infants ≤ 90-day-old over an 8-year period (2010–2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared. Results A total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0–243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0–250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD. Conclusions The LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.
Published: 2021

15. Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Author: Jackwee Lim, Kia Joo Puan, Liang Wei Wang, Karen Wei Weng Teng, Chiew Yee Loh, Kim Peng Tan, Guillaume Carissimo, Yi-Hao Chan, Chek Meng Poh, Cheryl Yi-Pin Lee, Siew-Wai Fong, Nicholas Kim-Wah Yeo, Rhonda Sin-Ling Chee, Siti Naqiah Amrun, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres-Ruesta, Norman Leo Fernandez, Wilson How, Anand Kumar Andiappan, Wendy Lee, Kaibo Duan, Seow-Yen Tan, Gabriel Yan, Shirin Kalimuddin, David Chien Lye, Yee-Sin Leo, Sean W. X. Ong, Barnaby E. Young, Laurent Renia, Lisa F. P. Ng, Bernett Lee, Olaf Rötzschke, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, and Saw Swee Hock School of Public Health, National University of Singapore
Subjects: Adult, Male, Immunology, Cytokine Profile, severity, Inflammation, cytokine profile, CD38, active infection, Cohort Studies, Post-Acute COVID-19 Syndrome, Immune system, immunophenotyping, medicine, Humans, Immunology and Allergy, Medicine [Science], Aged, Original Research, CD86, SARS-CoV-2, business.industry, COVID-19, Convalescence, Middle Aged, immune recovery, RC581-607, Vascular endothelial growth factor A, inflammation, SARS – CoV – 2, Female, Hepatocyte growth factor, Interleukin-3 receptor, Immunologic diseases. Allergy, medicine.symptom, business, CD8, medicine.drug
Abstract: Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of "long COVID-19", and defines key cells and cytokines that delineate true and quasi-convalescent states. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This work was supported by A*STAR Infectious Diseases Labs and Singapore Immunology Network (SIgN) core research grants, and the A*STAR COVID-19 Research funding (H/20/04/g1/006) provided to SIgN by the Biomedical Research Council (BMRC). Subject recruitment, sample collection and analyses were funded by the National Medical Research Council (NMRC) COVID-19 Research Fund (COVID19RF-001, COVID19-RF007, COVID190RF-060). The SIgN Immunomonitoring Platform is supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011. The SIgN Flow Cytometry and the Multiple Analyte Platforms were supported by a grant from the National Research Foundation, Immunomonitoring Service Platform ISP) (#NRF2017_SISFP09) and the National Research Foundation Singapore (NRF).
Published: 2021
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16. Persistent Symptoms and Association With Inflammatory Cytokine Signatures in Recovered Coronavirus Disease 2019 Patients

Author: Paul A. Tambyah, David C. Lye, Barnaby Edward Young, Yi-Hao Chan, Lisa F. P. Ng, Surinder Pada, Bernett Lee, Rhonda Sin-Ling Chee, Yee Sin Leo, Nicholas Kim-Wah Yeo, Ying Ding, Sean Wei Xiang Ong, Seow Yen Tan, Siew-Wai Fong, Laurent Rénia, Siti Naqiah Amrun, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: 0301 basic medicine, medicine.medical_specialty, Chronic Fatigue, medicine.medical_treatment, persistent symptoms, Inflammation, medicine.disease_cause, Gastroenterology, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, medicine, Major Article, Medicine [Science], 030212 general & internal medicine, Macrophage inflammatory protein, long-term, business.industry, Interleukin, COVID-19, Immune dysregulation, cytokines, Editor's Choice, 030104 developmental biology, Infectious Diseases, Cytokine, AcademicSubjects/MED00290, Oncology, Cytokines, medicine.symptom, business, chronic fatigue, Cohort study
Abstract: Background: The complications and sequelae of coronavirus disease 2019 (COVID-19) and their effect on long-term health are unclear, and the trajectory of associated immune dysregulation is poorly understood. Methods: We conducted a prospective longitudinal multicenter cohort study at 4 public hospitals in Singapore. Patients with COVID-19 were monitored for a median of 6 months after recovery from acute infection. Clinical symptoms and radiologic data were collected, along with plasma samples for quantification of immune mediators. The relationship between clinical symptoms and immune cytokine profiles was investigated. Results: Two hundred eighty-eight participants were recruited, and follow-up data were available for 183, 175, and 120 participants at days 30, 90, and 180 postsymptom onset, respectively. Symptoms related to COVID-19 were present in 31 (16.9%), 13 (7.4%), and 14 (11.7%) at days 30, 90, and 180. In a multivariable model, age >65 years, non-Chinese ethnicity, and the severity of acute infection were associated with increased likelihood of persistent symptoms. Recovered COVID-19 patients had elevated levels of proinflammatory interleukin (IL)-17A, stem cell factor, IL-12p70, and IL-1β and pro-angiogenic macrophage inflammatory protein 1β, brain-derived neurotrophic factor, and vascular endothelial growth factor at day 180 compared with healthy controls. Higher levels of monocyte chemoattractant protein-1 and platelet-derived growth factor-BB were detected in patients with persistent symptoms, versus symptom-free patients. Conclusions: Approximately 10% of recovered patients had persistent symptoms 6 months after initial infection. Immune cytokine signatures of the recovered patients reflected ongoing chronic inflammation and angiogenesis. Patients with COVID-19 should be monitored closely for emerging long-term health consequences. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version Recruitment of study participants and sample collection was funded by the Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001, COVID19RF-060) and A*STAR COVID-19 Research funding (H/20/04/g1/006). The SIgN Immunomonitoring Platform is supported by a BMRC IAF 311006 grant and BMRC transition funds (H16/99/b0/011). The SIgN MAP platform was supported by a grant from the National Research Foundation, Immunomonitoring Service Platform (NRF2017_SISFP09) from the National Research Foundation Singapore.
Published: 2021

17. Mechanisms of Resistance to PI3K Inhibitors in Cancer: Adaptive Responses, Drug Tolerance and Cellular Plasticity

Author: Pieter Johan Adam Eichhorn, Sarah Christine Elisabeth Wright, Violeta Serra, Jordi Rodon, Natali Vasilevski, Institut Català de la Salut, [Wright SCE, Vasilevski N] Faculty of Health Sciences, Curtin Medical School, Curtin University, Bentley 6102, Australia. Curtin Health Innovation Research Institute and Faculty of Health Sciences, Curtin University, Bentley 6102, Australia. [Serra V] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rodon J] MD Anderson Cancer Center, Investigational Cancer Therapeutics Department, Houston, TX 77030, USA. [Eichhorn PJA] Faculty of Health Sciences, Curtin Medical School, Curtin University, Bentley 6102, Australia. Curtin Health Innovation Research Institute and Faculty of Health Sciences, Curtin University, Bentley 6102, Australia. Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Cancer Research, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], Angiogenesis, Motility, Review, Biology, lcsh:RC254-282, neoplasias [ENFERMEDADES], 03 medical and health sciences, 0302 clinical medicine, PI3K pathway inhibitors, Drug tolerance, medicine, PI3K/AKT/mTOR pathway, Otros calificadores::/terapia [Otros calificadores], Resistència als medicaments, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], Hyperactivation, Cell growth, Càncer - Tractament, Cancer, Other subheadings::/therapy [Other subheadings], lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, PI3K pathway, Neoplasms [DISEASES], 030104 developmental biology, Oncology, Cellular plasticity, mechanisms of resistance, 030220 oncology & carcinogenesis, Neuroscience
Abstract: Simple Summary The phosphoinositide-3-kinase (PI3K) pathway is the most frequently activated pathway in human cancers. Consequently, a number of compounds targeting the various nodes of this pathway have been developed. However, the majority of these compounds have been unsuccessful in patients due to high levels of toxicity, as well as their inability to effectively downregulate the pathway to levels required for tumour responses. This inability to downregulate the pathway is partially mediated by intrinsic adaptive response, also known as compensatory mechanisms or feedback loops, which reactivate the pathway following inhibition; limiting the effectiveness of these compounds. In this review we highlight the mechanisms of action of these adaptive responses and highlight potential combinatorial strategies to delay tumour progression. Abstract The phosphatidylinositol-3-kinase (PI3K) pathway plays a central role in the regulation of several signalling cascades which regulate biological processes such as cellular growth, survival, proliferation, motility and angiogenesis. The hyperactivation of this pathway is linked to tumour progression and is one of the most common events in human cancers. Additionally, aberrant activation of the PI3K pathway has been demonstrated to limit the effectiveness of a number of anti-tumour agents paving the way for the development and implementation of PI3K inhibitors in the clinic. However, the overall effectiveness of these compounds has been greatly limited by inadequate target engagement due to reactivation of the pathway by compensatory mechanisms. Herein, we review the common adaptive responses that lead to reactivation of the PI3K pathway, therapy resistance and potential strategies to overcome these mechanisms of resistance. Furthermore, we highlight the potential role in changes in cellular plasticity and PI3K inhibitor resistance.
Published: 2021

18. H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions

Author: Greg Tucker-Kellogg, Ying Zhang, Zhendong Cao, Mei Chee Lim, Yichao Cai, Melissa J. Fullwood, Shang Li, Erez Lieberman Aiden, Yan Ping Loh, Lakshmanan Manikandan, Anandhkumar Raju, Vinay Tergaonkar, Jia Qi Tng, School of Biological Sciences, Cancer Science Institute of Singapore, National University of Singapore, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Department of Biological Sciences, National University of Singapore, Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Computational Biology Programme, National University of Singapore, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Department of Genetics, Baylor College of Medicine, and Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania
Subjects: 0301 basic medicine, General Physics and Astronomy, Genome, Histones, Gene Knockout Techniques, Mice, 0302 clinical medicine, Neoplasms, Gene expression, CRISPR, RNA-Seq, Regulation of gene expression, Multidisciplinary, biology, Silencers, Phenotype, Chromatin, Cell biology, Gene Expression Regulation, Neoplastic, Histone, Biological sciences::Molecular biology [Science], Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Chromatin Immunoprecipitation Sequencing, Epigenetics, Female, Transcription, Science, Epigenetic code, macromolecular substances, Epigenetic Repression, Chromatin structure, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Downregulation and upregulation, Insulin-Like Growth Factor II, Cell Line, Tumor, Silencer Elements, Transcriptional, Animals, Humans, Cancer models, Enhancer, Gene, Gene knockout, General Chemistry, Xenograft Model Antitumor Assays, Gene regulation, Fibroblast Growth Factors, 030104 developmental biology, biology.protein, Function (biology)
Abstract: The mechanisms underlying gene repression and silencers are poorly understood. Here we investigate the hypothesis that H3K27me3-rich regions of the genome, defined from clusters of H3K27me3 peaks, may be used to identify silencers that can regulate gene expression via proximity or looping. We find that H3K27me3-rich regions are associated with chromatin interactions and interact preferentially with each other. H3K27me3-rich regions component removal at interaction anchors by CRISPR leads to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. Cells with H3K27me3-rich regions knockout also show changes in phenotype associated with cell identity, and altered xenograft tumor growth. Finally, we observe that H3K27me3-rich regions-associated genes and long-range chromatin interactions are susceptible to H3K27me3 depletion. Our results characterize H3K27me3-rich regions and their mechanisms of functioning via looping., Mechanisms underlying gene repression and silencers remain poorly understood. Here the authors investigate the role of H3K27me3-rich regions in the genome, as defined from clusters of H3K27me3 peaks, in regulating gene expression via looping.
Published: 2021

19. A community-enabled readiness for first 1000 days learning ecosystem (CRADLE) for first-time families: study protocol of a three-arm randomised controlled trial

Author: Kee Chong Ng, Oh. Moh Chay, Joyce Teo, See Ling Loy, Nurul Khairani Binte Abdul Razak, Thilagamangai, Sze Wern Chan, Lee Kong Chian School of Medicine (LKCMedicine), Duke-NUS Medical School, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: Parents, Choice Architecture, medicine.medical_specialty, Psychological intervention, Mothers, Medicine (miscellaneous), law.invention, Study Protocol, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Pregnancy, law, First-Time Parent, Choice architecture, medicine, Humans, Childbirth, Pharmacology (medical), Medicine [Science], 030212 general & internal medicine, Early childhood, Child, Ecosystem, Randomized Controlled Trials as Topic, Randomised controlled trial, Self-efficacy, Singapore, lcsh:R5-920, Nudge, 030219 obstetrics & reproductive medicine, Parenting, business.industry, First-time parent, Infant, Newborn, Midwife, medicine.disease, Test (assessment), Child, Preschool, Family medicine, Female, lcsh:Medicine (General), business
Abstract: Background Enhanced parenting self-efficacy (PSE) contributes to positive parenting and future parental-child health. First-time parents, in particular, are in need of support since the pregnancy until post-delivery to strengthen their early PSE. However, there is a lack of effective and sustainable relevant programmes in the community. The Community-enabled Readiness for first 1000 Days Learning Ecosystem (CRADLE) aims to develop a self-learning eco-community throughout the pregnancy and early childhood to promote PSE among first-time parents. We apply choice architecture strategy using behavioural nudges and midwife-led continuity care during the first 1000 days, and test their effects on PSE and mother-child health for first-time families in Singapore. Methods This three-arm randomised controlled trial will recruit up to 750 pregnant women from the KK Women’s and Children’s Hospital, Singapore. Participants will be randomly assigned to receive: (1) standard routine care; (2) behavioural nudges (text messages) along with the use of a social media platform; or (3) midwife-led continuity care involving individualised teleconferencing sessions, during pregnancy and post-delivery. Using web-based questionnaires, participants will be assessed for baseline socio-demography and health status in the first visit, with follow-up assessments in the third trimester, at birth, 6-week (primary end-point), 6-, 12-, 18- and 24-month post-delivery. The primary outcome is PSE. Secondary outcomes include health and birth experience, mental wellness, feeding practice, maternal and child nutritional status. Intention-to-treat and per-protocol analyses will be performed using general linear models to test the effects of interventions across three arms. Recruitment has begun in June 2020 and is estimated to complete in September 2022. Discussion This study may identify a sustainable effective strategy in the community by helping first-time parents to have a positive experience during the pregnancy, childbirth and parenthood, leading to an enhanced PSE and health outcomes for both mother and child. Findings from this study will provide insight into the implementation of early parenting and mother-child care programmes. Trial registration ClinicalTrials.gov NCT04275765. Registered on 19 February 2020.
Published: 2021

20. A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

Author: Barry Halliwell, Camilo Libedinsky, Gil Gerald Lasam Gammad, Xiang Zheng, Muthu Kumar Gnanasammandhan, Chou Chai, Yanzhuang Yeo, Robert Alan Jappy Tucker, Fengyuan Yang, Daniel Boon Loong Teh, Yong Zhang, Nagarjun Bolem, Kah-Leong Lim, Brian K. Kennedy, Gavin S. Dawe, Bing Cheng Wu, Tan Boon Toh, Zhendong Lei, Edward Kai-Hua Chow, John S. Ho, Wei-Yi Ong, Akshaya Bansal, Lissa Hooi, Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: Materials science, medicine.medical_treatment, Photodynamic therapy, 02 engineering and technology, 010402 general chemistry, Light delivery, 01 natural sciences, Polyethylene Glycols, Mice, Mouse xenograft, Cell Line, Tumor, medicine, Animals, Medicine [Science], General Materials Science, Photosensitizer, Optical Fibers, Photosensitizing Agents, Brain Neoplasms, Mechanical Engineering, Hydrogels, Aminolevulinic Acid, equipment and supplies, 021001 nanoscience & nanotechnology, Biocompatible material, Photon upconversion, 0104 chemical sciences, Cell Transformation, Neoplastic, Photochemotherapy, Mechanics of Materials, Self-healing hydrogels, Nanoparticles, Implant, 0210 nano-technology, Glioblastoma, Wireless Technology, Biomedical engineering
Abstract: Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery. Ministry of Education (MOE) Nanyang Technological University This work was supported by National University of Singapore’s start up grants, R-183-000-413-733 and R-185-000-363-733; Singapore’s Ministry of Education grants (MOE 2016-T3-1-004, R-397-000-274-112, R-397-000-270-114); and a Lee Kong Chian School of Medicine, Nanyang Technological University start-up grant.
Published: 2020

21. Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases

Author: Elena Sumarokova, Gina Gualano, Evgeny Belilovski, Armine Izadifar, Eva Tabernero, Pierre Bachez, Alessandro Torre, Maria Luiza de Souza-Galvão, François-Xavier Blanc, Claire Andrejak, Mathilde Fréchet Jachym, Denise Rossato Silva, Paolo Scarpellini, Margarita Marín Royo, Dina Visca, Ángel Domínguez-Castellano, Teresa Rodrigo, Antoine Froissart, Damien Le Dû, Giovanni Sotgiu, Antonio Spanevello, Pierre-Alexandre Bart, Simon Tiberi, Miguel Zabaleta Murguiondo, Frédéric Schlemmer, Marina Tadolini, Rosella Centis, Matteo Saporiti, Sergey Borisov, Giovanni Battista Migliori, Vania Giacomet, Delia Goletti, Frédéric Rivière, Ilaria Motta, Samir Dourmane, Soazic Grard, José Cardoso-Landivar, José-María García-García, Jesica Mazza-Stalder, Fabrizio Palmieri, Luigi Codecasa, Catherine W.M. Ong, Adrián Sánchez-Montalvá, Lia D'Ambrosio, Jan-Willem C. Alffenaar, Paul A. Tambyah, Tadolini M., Codecasa L.R., Garcia-Garcia J.-M., Blanc F.-X., Borisov S., Alffenaar J.-W., Andrejak C., Bachez P., Bart P.-A., Belilovski E., Cardoso-Landivar J., Centis R., D'Ambrosio L., De Souza-Galvao M.-L., Dominguez-Castellano A., Dourmane S., Jachym M.F., Froissart A., Giacomet V., Goletti D., Grard S., Gualano G., Izadifar A., Le Du D., Royo M.M., Mazza-Stalder J., Motta I., Min Ong C.W., Palmieri F., Riviere F., Rodrigo T., Silva D.R., Sanchez-Montalva A., Saporiti M., Scarpellini P., Schlemmer F., Spanevello A., Sumarokova E., Tabernero E., Tambyah P.A., Tiberi S., Torre A., Visca D., Murguiondo M.Z., Sotgiu G., Migliori G.B., Centre hospitalier universitaire de Nantes (CHU Nantes), University Medical Center Groningen [Groningen] (UMCG), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Henri Mondor, Centre Hospitalier Intercommunal de Créteil (CHIC), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Hôpital Raymond Poincaré [AP-HP], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Maturation des proteines, destinée cellulaire et thérapeutique (PROMTI), Département Biologie des Génomes (DBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Aristotle University of Thessaloniki, [Tadolini,m] Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy. [Codecasa,LR, Saporiti,M] TB Reference Centre, Villa Marelli Institute, Niguarda Hospital, Milan, Italy. [García-García,JM, Rodrigo,T]Tuberculosis Research Programme (PII-TB), SEPAR, Barcelona, Spain. [Blanc,FX] Centre Hospitalier Universitaire, Nantes, France. [Borisov,S, Belilovski,E, Sumarokova,E] Moscow Research and Clinical Center for TB Control, Moscow, Russian Federation. [Alffenaar,JW] The University of Sydney, Sydney Pharmacy School, Sydney, Australia. [Alffenaar,JW] Westmead Hospital, Sydney, Australia. [Alffenaar,JW] Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia. [Andréjak,C] Service de Pneumologie CHU AMIENS PICARDIE, France AND UR Université de Picardie Jules Verne, Amiens, France. [Bachez,P] Service de Pneumologie, Clinique Saint Luc, Bouge, Belgium. [Bart,PA] Dept of Internal Medicine, Lausanne University, Lausanne, Switzerland. [Cardoso-Landivar,J] Servicio Neumología, Vall D´Hebron University Hospital, Barcelona, Spain. [Centis,R] Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy. [D'Ambrosio,L] Public Health Consulting Group, Lugano, Switzerland. [Dominguez-Castellano,A] Servicio de Enfermedades Infecciosas y Microbiología, Hospital Virgen Macarena, Sevilla, Spain. [Dourmane,S] Service de Pneumologie, Groupe hospitalier sud île de France (GHSIF), Melun, France. [Fréchet Jachym,M, Le Du,D] Centre Hospitalier de Bligny, Briis Sous Forges, France. [Froissart,A] Service de Médecine interne, CHI de Créteil, Créteil, France. [Giacomet,V]20Pediatric Infectious Diseases Unit, Dept of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Milan, Italy. [Goletti,D] Translational Research Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy. [Grard,S] Centre de Lutte Antituberculeuse (CLAT 38), Grenoble, France. [Gualano,G, Palmieri,F] Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases 'L. Spallanzani', IRCCS, Rome, Italy. [Izadifar,A] Hôpital Européen de Paris La Roseraie, Aubervilliers, France. [Marín Royo,M] Servicio Neumología, Hospital General Universitario de Castellón, Castelló, Spain. [Mazza-Stalder,J] Pulmonary Division, Lausanne University Hospital CHUV, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. [Motta,I] Dipartimento di Scienze Mediche, Clinica Universitaria Malattie Infettive, Ospedale Amedeo di Savoia, Torino, Italia. [Ong,CWM, Tambyah,PA] Dept of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. [Ong,CWM, Tambyah,PA] Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore. [Rivière,F] Hôpital d'Instruction des Armées (HIA) Percy, Clamart, France. [Silva,DR] Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil. [Sánchez-Montalvá,A]Infectious Diseases Dept, International Health and Tuberculosis Unit, Vall d'Hebron University Hospital, Barcelona, Spain. [Sánchez-Montalvá,A] Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain. [Sánchez-Montalvá,A] Grupo de Estudio de Infecciones por Micobacterias (GEIM), Spanish Society of Infectious Diseases (SEIMC), Spain. [Scarpellini,P] Unit of Infectious Diseases, Università Vita e Salute, San Raffaele Hospital, Milan, Italy. [Schlemmer,F] Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France. [Spanevello,A, Visca,D] Division of Pulmonary Rehabilitation, Istituti Clinici Scientifici Maugeri, IRCCS, Tradate, Italy. [Spanevello,A, Visca,D] Dept of Medicine and Surgery, Respiratory Diseases, University of Insubria, Tradate, Italy. [Tabernero,E] Servicio Neumología, Hospital de Cruces, Bilbao, Spain. [Tiberi,S] Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. [Tiberi,S] Division of Infection, Royal London Hospital, Barts Health NHS Trust, London, UK. [Torre,A] Dept of Infectious Diseases, University of Milan, L. Sacco Hospital, Milan, Italy. [Zabaleta Murguiondo,M] Servicio Neumología Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Sotgiu,G] Clinical Epidemiology and Medical Statistics Unit, Dept of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy. [Migliori,GB] Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy., and CHU Henri Mondor [Créteil]
Subjects: Male, Pediatrics, Adult, Aged, Antitubercular Agents/therapeutic use, Antiviral Agents/therapeutic use, Azithromycin/therapeutic use, Betacoronavirus, Clinical Laboratory Techniques, Cohort Studies, Coinfection, Coronavirus Infections/complications, Coronavirus Infections/diagnosis, Coronavirus Infections/drug therapy, Drug Combinations, Emigrants and Immigrants, Female, Humans, Hydroxychloroquine/therapeutic use, Lopinavir/therapeutic use, Lung/diagnostic imaging, Middle Aged, Mortality, Pandemics, Pneumonia, Viral/complications, Pneumonia, Viral/diagnosis, Pneumonia, Viral/drug therapy, Ritonavir/therapeutic use, Tomography, X-Ray Computed, Tuberculosis/complications, Tuberculosis/diagnosis, Tuberculosis/drug therapy, Tuberculosis, Pulmonary/complications, Tuberculosis, Pulmonary/diagnosis, Tuberculosis, Pulmonary/drug therapy, [SDV]Life Sciences [q-bio], viruses, Antitubercular Agents, Azithromycin, Clinical Laboratory Technique, Lopinavir, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Sequelae, Antitubercular Agent, 0302 clinical medicine, COVID-19 Testing, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography [Medical Subject Headings], Drug Combination, 030212 general & internal medicine, Viral, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques [Medical Subject Headings], Lung, Tomography, ComputingMilieux_MISCELLANEOUS, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Vital Statistics::Mortality [Medical Subject Headings], virus diseases, Pulmonary, respiratory system, X-Ray Computed, Impactos en la salud, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography [Medical Subject Headings], Cohort, Coronavirus Infections, medicine.drug, Cohort study, Human, Hydroxychloroquine, Impacts on health, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Tuberculosis, Tuberculosi, Infecciones por coronavirus, Estudios de cohortes, Pneumonia, Viral, Antiviral Agents, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Actinomycetales Infections::Mycobacterium Infections::Tuberculosis [Medical Subject Headings], 03 medical and health sciences, Tuberculosis diagnosis, medicine, Research Letter, Tuberculosis, Pulmonary, Secuelas, Ritonavir, Antiviral Agent, Pandemia, Betacoronaviru, Pandemic, business.industry, Coronavirus Infection, SARS-CoV-2, COVID-19, Emigrants and Immigrant, Pneumonia, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents::Antitubercular Agents [Medical Subject Headings], medicine.disease, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], COVID-19 Drug Treatment, Coronavirus, 030228 respiratory system, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cohort Studie, business
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3–5].
Published: 2020
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22. Next-generation ARIA care pathways for rhinitis and asthma: A model for multimorbid chronic diseases

Author: Bousquet, J.J. and Schünemann, H.J. and Togias, A. and Erhola, M. and Hellings, P.W. and Zuberbier, T. and Agache, I. and Ansotegui, I.J. and Anto, J.M. and Bachert, C. and Becker, S. and Bedolla-Barajas, M. and Bewick, M. and Bosnic-Anticevich, S. and Bosse, I. and Boulet, L.P. and Bourrez, J.M. and Brusselle, G. and Chavannes, N. and Costa, E. and Cruz, A.A. and Czarlewski, W. and Fokkens, W.J. and Fonseca, J.A. and Gaga, M. and Haahtela, T. and Illario, M. and Klimek, L. and Kuna, P. and Kvedariene, V. and Le, L.T.T. and Larenas-Linnemann, D. and Laune, D. and Lourenço, O.M. and Menditto, E. and Mullol, J. and Okamoto, Y. and Papadopoulos, N. and Pham-Thi, N. and Picard, R. and Pinnock, H. and Roche, N. and Roller-Wirnsberger, R.E. and Rolland, C. and Samolinski, B. and Sheikh, A. and Toppila-Salmi, S. and Tsiligianni, I. and Valiulis, A. and Valovirta, E. and Vasankari, T. and Ventura, M.-T. and Walker, S. and Williams, S. and Akdis, C.A. and Annesi-Maesano, I. and Arnavielhe, S. and Basagana, X. and Bateman, E. and Bedbrook, A. and Bennoor, K.S. and Benveniste, S. and Bergmann, K.C. and Bialek, S. and Billo, N. and Bindslev-Jensen, C. and Bjermer, L. and Blain, H. and Bonini, M. and Bonniaud, P. and Bouchard, J. and Briedis, V. and Brightling, C.E. and Brozek, J. and Buhl, R. and Buonaiuto, R. and Canonica, G.W. and Cardona, V. and Carriazo, A.M. and Carr, W. and Cartier, C. and Casale, T. and Cecchi, L. and Cepeda Sarabia, A.M. and Chkhartishvili, E. and Chu, D.K. and Cingi, C. and Colgan, E. and De Sousa, J.C. and Courbis, A.L. and Custovic, A. and Cvetkosvki, B. and Damato, G. and Da Silva, J. and Dantas, C. and Dokic, D. and Dauvilliers, Y. and Dedeu, A. and De Feo, G. and Devillier, P. and Di Capua, S. and Dykewickz, M. and Dubakiene, R. and Ebisawa, M. and El-Gamal, Y. and Eller, E. and Emuzyte, R. and Farrell, J. and Fink-Wagner, A. and Fiocchi, A. and Fontaine, J.F. and Gemicioǧlu, B. and Schmid-Grendelmeir, P. and Gamkrelidze, A. and Garcia-Aymerich, J. and Gomez, M. and Diaz, S.G. and Gotua, M. and Guldemond, N.A. and Guzmán, M.-A. and Hajjam, J. and O'Hourihane, J.B. and Humbert, M. and Iaccarino, G. and Ierodiakonou, D. and Ivancevich, J.C. and Joos, G. and Jung, K.-S. and Jutel, M. and Kaidashev, I. and Kalayci, O. and Kardas, P. and Keil, T. and Khaitov, M. and Khaltaev, N. and Kleine-Tebbe, J. and Kowalski, M.L. and Kritikos, V. and Kull, I. and Leonardini, L. and Lieberman, P. and Lipworth, B. and Lodrup Carlsen, K.C. and Loureiro, C.C. and Louis, R. and Mair, A. and Marien, G. and Mahboub, B. and Malva, J. and Manning, P. and De Manuel Keenoy, E. and Marshall, G.D. and Masjedi, M.R. and Maspero, J.F. and Mathieu-Dupas, E. and Matricardi, P.M. and Melén, E. and Melo-Gomes, E. and Meltzer, E.O. and Mercier, J. and Miculinic, N. and Mihaltan, F. and Milenkovic, B. and Moda, G. and Mogica-Martinez, M.-D. and Mohammad, Y. and Montefort, S. and Monti, R. and Morais-Almeida, M. and Mösges, R. and Münter, L. and Muraro, A. and Murray, R. and Naclerio, R. and Napoli, L. and Namazova-Baranova, L. and Neffen, H. and Nekam, K. and Neou, A. and Novellino, E. and Nyembue, D. and O'Hehir, R. and Ohta, K. and Okubo, K. and Onorato, G. and Ouedraogo, S. and Pali-Schöll, I. and Palkonen, S. and Panzner, P. and Park, H.-S. and Pépin, J.-L. and Pereira, A.-M. and Pfaar, O. and Paulino, E. and Phillips, J. and Plavec, D. and Popov, T.A. and Portejoie, F. and Price, D. and Prokopakis, E.P. and Pugin, B. and Raciborski, F. and Rajabian-Söderlund, R. and Reitsma, S. and Rodo, X. and Romano, A. and Rosario, N. and Rottem, M. and Ryan, D. and Salimäki, J. and Sanchez-Borges, M.M. and Sisul, J.-C. and Solé, D. and Somekh, D. and Sooronbaev, T. and Sova, M. and Spranger, O. and Stellato, C. and Stelmach, R. and Ulrik, C.S. and Thibaudon, M. and To, T. and Todo-Bom, A. and Tomazic, P.V. and Valero, A.A. and Valenta, R. and Valentin-Rostan, M. and Van Der Kleij, R. and Vandenplas, O. and Vezzani, G. and Viart, F. and Viegi, G. and Wallace, D. and Wagenmann, M. and Wang, D.Y. and Waserman, S. and Wickman, M. and Williams, D.M. and Wong, G. and Wroczynski, P. and Yiallouros, P.K. and Yorgancioglu, A. and Yusuf, O.M. and Zar, H.J. and Zeng, S. and Zernotti, M. and Zhang, L. and Zhong, N.S. and Zidarn, M., MACVIA-France, Fondation Partenariale FMC VIA-LR, CHU, Montpellier Cedex 5, 34295, France, INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny Le Bretonneux, France, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Brussels, Belgium, Humboldt-Uniersität zu Berlin, Berlin, Germany, Department of Dermatology and Allergy, Comprehensive Allergy-Centre, Berlin Institute of Health, Berlin, Germany, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada, Division of Allergy, Immunology, and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States, National Institute for Health and Welfare, Helsinki, Finland, Dept. of Otorhinolaryngology, Univ Hospitals Leuven, Louvain, Belgium, Academic Medical Center, Univ of Amsterdam, Amsterdam, Netherlands, Faculty of Medicine, Transylvania University, Brasov, Romania, Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, Spain, ISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, IMIM (Hospital del Mar Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, Upper Airways Research Laboratory, ENT Dept., Ghent University Hospital, Ghent, Belgium, Dept. of Otolaryngology, Head and Neck Surgery, University of Mainz, Mainz, Germany, Hospital Civil de Guadalajara Dr Juan I Menchaca, Guadalarara, Mexico, iQ4U Consultants Ltd., London, United Kingdom, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia, Woolcock Emphysema Centre, Sydney, Australia, Sydney Local Health District, Glebe, NSW, Australia, La Rochelle, France, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada, EIT Health France, Paris, France, Dept. of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands, UCIBIO, REQUINTE, Faculty of Pharmacy, Competence Center on Active and Healthy Ageing, University of Porto (Porto4Ageing), Porto, Portugal, ProAR-Nucleo de Excelencia em Asma, Federal University of Bahia, Bahia, Brazil, WHO GARD Planning Group, Salvador, Brazil, Medical Consulting Czarlewski, Levallois, France, Department of Otorhino-Laryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda Porto, Portugal, Athens Chest Hospital, 7th Resp. Med. Dept. and Asthma Center, Athens, Greece, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland, Division for Health Innovation, Campania Region and Federico II University Hospital Naples (R and D and DISMET), Naples, Italy, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Łódź, Poland, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, University of Medicine and Pharmacy, Hochiminh City, Viet Nam, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, KYomed INNOV, Montpellier, France, Faculty of Health Sciences and CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal, CIRFF, Federico II University, Naples, Italy, Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, Barcelona, Spain, Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Dept. of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan, Division of Infection, Immunity and Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, 2nd Pediatric Clinic, Athens General Children's Hospital P and A Kyriakou, University of Athens, Athens, Greece, Allergy Department, Pasteur Institute, Paris, France, Conseil General de l'Economie Ministere de l'Economie, de l'Industrie et du Numerique, Paris, France, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom, Pneumologie et Soins Intensifs Respiratoires, Hôpitaux Universitaires Paris, Centre Hôpital Cochin, Paris, France, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Association Asthme et Allergie, Paris, France, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Health Planning Unit, Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece, International Primary Care Respiratory Group IPCRG, Aberdeen, United Kingdom, Institute of Clinical Medicine, Institute of Health Sciences, Vilnius University, Faculty of Medicine, Vilnius, Lithuania, Department of Lung Diseases and Clinical Immunology, University of Turku and Terveystalo Allergy Clinic, Turku, Finland, FILHA, Finnish Lung Association, Helsinki, Finland, Unit of Geriatric Immunoallergol-ogy, University of Bari Medical School, Bari, Italy, Asthma UK, Mansell Street, London, United Kingdom, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland, Epidemiology of Allergic and Respiratory Diseases, Department Institute Pierre Louis of Epidemiology and Public Health, INSERM and Sorbonne Université, Medical School Saint Antoine, Paris, France, Department of Medicine, University of Cape Town, Cape Town, South Africa, Dept. of Respiratory Medicine, National Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh, National Center of Expertise in Cognitive Stimulation (CEN STIMCO), Broca Hospital, Paris, France, Department of Biochemistry and Clinical Chemistry, Faculty of Pharmacy, Division of Laboratory Medicine, Warsaw Medical University, Warsaw, Poland, Global Alliance Against Chronic Respiratory Diseases (WHO GARD), Joensuu, Finland, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Termofscher Scientific, Uppsala, Sweden, Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden, Department of Geriatrics, Montpellier University hospital, Montpellier, France, EA 2991 Euromov, University Montpellier, Montpellier, France, UOC Pneumologia, Istituto di Medicina Interna, F Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy, National Heart and Lung Institute, Royal Brompton Hospital, Imperial College, London, United Kingdom, CHU, Dijon, France, Clinical Medicine, Laval's University, Quebec City, Canada, Medicine Department, Hôpital de la Malbaie, Quebec city, QC, Canada, Department of Clinical Pharmacy of Lithuanian, University of Health, Kaunas, Lithuania, Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, United Kingdom, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany, Municipality Pharmacy, Sarno, Italy, Personalized Medicine Clinic Asthma and Allergy, Humanitas University, Humanitas Research Hospital, Rozzano, Milan, Italy, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron, ARADyAL Research Network, Barcelona, Spain, Regional Ministry of Health of Andalu-sia, Seville, Spain, Allergy and Asthma Associates of Southern California, Mission Viejo, CA, United States, ASA-Advanced Solutions Accelerator, Clapiers, France, Division of Allergy/Immunology, University of South Florida, Tampa, FL, United States, SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy, Allergy and Immunology Laboratory, Metropolitan University, Simon Bolivar University, Barranquilla, Colombia, SLaai, Sociedad Lati-noamericana de Allergia, Asma e Immunologia, Barranquilla, Colombia, Chachava Clinic, David Tvildiani Medical University-AIETI Medical School, Grigol Robakidze University, Tbilisi, Georgia, Medical Faculty, ENT Department, Eskisehir Osmangazi University, Eskisehir, Turkey, Department of Health, Social Services and Public Safety, Belfast, Northern Ireland, United Kingdom, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal, PT Government Associate Laboratory, ICVS/3B's, Braga/Guimarães, Portugal, Ecole des Mines, Alès, France, Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester, University Hospital of South Manchester, Manchester, United Kingdom, Division of Respiratory and Allergic Diseases, Department of Respiratory Diseases, High Specialty Hospital A. Cardarelli, Naples, Italy, Allergy Service, University Hospital of Federal University of Santa Catarina (HU-UFSC), Florianópolis, Brazil, Cáritas Diocesana de Coimbra, Coimbra, Portugal, Ageing at Coimbra EIP-AHA Reference Site, Coimbra, Portugal, Medical Faculty Skopje, University Clinic of Pulmonology and Allergy, Skopje, North Macedonia, Sleep Unit, Department of Neurology, Hôpital Gui-de-Chauliac Montpellier, Inserm U1061, Montpellier, France, AQuAS, Barcelna, Spain, EUREGHA, European Regional and Local Health Association, Brussels, Belgium, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, University of Salerno, Salerno, Italy, UPRES EA220, Pôle des Maladies des Voies Respiratoires, Hôpital Foch, Université Paris-Saclay, Suresnes, France, Farmacie Dei Golfi Group, Massa Lubrense, Italy, Section of Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, United States, Clinic of Infectious, Chest Diseases, Dermatology and Allergology, Vilnius University, Vilnius, Lithuania, Clinical Reserch Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan, Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt, Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Global Allergy and Asthma Platform GAAPP, Vienna, Austria, Division of Allergy, Department of Pediatric Medicine, Bambino Gesù Children's Research Hospital Holy See, Rome, Italy, Reims, France, Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istambul, Turkey, Allergy Unit, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland, National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia, Allergy and Asthma Unit, Hospital San Bernardo Salta, Salta, Argentina, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico, Center of Allergy and Immunology, Georgian Association of Allergology and Clinical Immunology, Tbilisi, Georgia, Institute of Health Policy and Management iBMG, Erasmus University, Rotterdam, Netherlands, Immunology and Allergy Division, Clinical Hospital, University of Chile, Santiago, Chile, Centich: Centre d'Expertise National des Technologies de l'Information et de la Communication pour l'Autonomie, Gérontopôle Autonomie Longévité des Pays de la Loire, Conseil Régional des Pays de la Loire, Centre d'Expertise Partenariat Europeen d'Innovation pour un Vieillissement Actif et en Bonne Sante, Nantes, France, Department of Paediatrics and Child Health, University College Cork, Cork, Ireland, Université Paris-Sud, Service de Pneumologie, Hôpital Bicêtre, Inserm UMR-S999, Le Kremlin Bicêtre, France, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, South Korea, Department of Clinical Immunology, Wrocław Medical University, Wrocław, Poland, Ukrainian Medical Stomatological Academy, Poltava, Ukraine, Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey, First Department of Family Medicine, Medical University of Lodz, Łódź, Poland, Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany, Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Würzburg, Germany, National Research Center, Institute of Immunology, Federal Medicobiological Agency, Laboratory of Molecular Immunology, Moscow, Russian Federation, GARD, Geneva, Switzerland, Allergy and Asthma Center Westend, Berlin, Germany, Department of Immunology and Allergy, Healthy Ageing Research Center, Medical University of Lodz, Łódź, Poland, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden, Sach's Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Mattone Internazionale Program, Veneto Region, Italy, Departments of Internal Medicine and Pediatrics (Divisions of Allergy and Immunology), University of Tennessee College of Medicine, Germantown, TN, United States, Scottish Centre for Respiratory Research, Cardiovascular and Diabetes Medicine, Medical Research Institute, Ninewells Hospital, University of Dundee, Dundee, United Kingdom, Department of Paediatrics, Oslo University Hospital, Oslo, Norway, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, Imunoalergologia, Centro Hospitalar Universitário de Coimbra, Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Department of Pulmonary Medicine, CHU Sart-Tilman, GIGA I3 Research Group, Liege, Belgium, DG for Health and Social Care, Scottish Government, Edinburgh, United Kingdom, Department of Pulmonary Medicine, Rashid Hospital, Dubai, United Arab Emirates, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Department of Medicine (RCSI), Bon Secours Hospital, Glasnevin, Dublin, Ireland, Kronikgune, International Centre of Excellence in Chronicity Research Barakaldo, Barakaldo, Bizkaia, Spain, Division of Clinical Immunology and Allergy, Laboratory of Behavioral Immunology Research, University of Mississippi Medical Center, Jackson, MS, United States, Tobacco Control Research Centre, Iranian Anti Tobacco Association, Tehran, Iran, Argentine Association of Allergy and Clinical Immunology, Buenos Aires, Argentina, Department of Pediatric Pneumology and Immunology, AG Molecular Allergology and Immunomodulation, Charité Medical University, Berlin, Germany, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, PNDR, Portuguese National Programme for Respiratory Diseases, Faculdade de Medicina de Lisboa, Lisbon, Portugal, Allergy and Asthma Medical Group and Research Center, San Diego, CA, United States, Department of Physiology, CHRU, University Montpellier, PhyMedExp, INSERM U1046, CNRS, UMR 9214, Montpellier, France, Croatian Pulmonary Society, Zagreb, Croatia, National Institute of Pneumology M Nasta, Bucharest, Romania, Clinic for Pulmonary Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbian Association for Asthma and COPD, Belgrade, Serbia, Regione Piemonte, Turin, Italy, Mexico City, Mexico, National Center for Research in Chronic Respiratory Diseases, Tishreen University School of Medicine, Latakia, Syrian Arab Republic, Syrian Private University, Damascus, Syrian Arab Republic, Faculty of Medicine and Surgery, University of Medicine, La Valette, Malta, Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino, Mauriziano Hospital, Turin, Italy, Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Cologne, Germany, CRI-Clinical Research International-Ltd, Hamburg, Germany, Danish Commitee for Health Education, Copenhagen East, Denmark, Food Allergy Referral Centre Veneto Region, Department of Women and Child Health, Padua General University Hospital, Padua, Italy, MedScript Ltd., Paraparomu, New Zealand, OPC, Cambridge, United Kingdom, Johns Hopkins School of Medicine, Baltimore, MD, United States, Consortium of Pharmacies and Services COSAFER, Salerno, Italy, Scientific Centre of Children's Health under the Russian Academy of Medical Sciences, Moscow, Russian Federation, Center of Allergy, Immunology and Respiratory Diseases, Santa Fe, Argentina, Center for Allergy and Immunology, Santa Fe, Argentina, Hospital of the Hospitaller Brothers in Buda, Budapest, Hungary, Die Hautambulanz and Rothhaar Study Center, Berlin, Germany, Department of Pharmacy, University of Naples Federico II, Naples, Italy, ENT Department, University Hospital of Kinshasa, Kinshasa, Democratic Republic Congo, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia, Dept. of Otolaryngology, Nippon Medical School, Tokyo, Japan, Centre Hospitalier Universitaire Pédiatrique Charles de Gaulle, Ouagadougou, Burkina Faso, Dept. of Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine and Medical University, Vienna, Austria, EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium, Department of Immunology and Allergology, Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic, Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea, Laboratoire HP2, Université Grenoble Alpes, Grenoble, France, INSERM, U1042, CHU de Grenoble, Grenoble, France, Allergy Unit, CUF-Porto Hospital and Institute, Porto, Portugal, Center for Research in Health Technologies and Information Systems, CINTESIS, Universidade do Porto, Porto, Portugal, Maladies Infectieuses et immunitaires, CHUL, Quebec City, QC, Canada, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany, Farmacias Holon, Lisbon, Portugal, Centre for Empowering Patients and Communities, Faulkland, Somerset, United Kingdom, Children's Hospital Srebrnjak, Zagreb, Croatia, School of Medicine, University J.J. Strossmayer, Osijek, Croatia, University Hospital 'Sv Ivan Rilski', Sofia, Bulgaria, Academic Centre of Primary Care, University of Aberdeen, Aberdeen, United Kingdom, Research in Real-Life, Cambridge, United Kingdom, Department of Otorhinolaryngology, University of Crete School of Medicine, Heraklion, Greece, Department of Nephrology and Endocrinology, Karolinska University Hospital, Stockholm, Sweden, Allergy Unit, Presidio Columbus, Catholic University of Sacred Heart, Rome, Italy, IRCCS Oasi Maria SS, Troina, Italy, Hospital de Clinicas, University of Parana, Paraná, Brazil, Division of Allergy Asthma and Clinical Immunology, Emek Medical Center, Afula, Israel, Allergy and Respiratory Research Group, University of Edinburgh, Edinburgh, United Kingdom, Association of Finnish Pharmacists, Helsinki, Finland, Allergy and Clinical Immunology Department, Centro Médico-Docente la, Trinidad and Clínica El Avila, Caracas, Venezuela, Sociedad Paraguaya de Alergia Asma e Inmunologia, Asunción, Paraguay, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil, European Health Futures Forum (EHFF), Dromahair, United Kingdom, Kyrgyzstan National Centre of Cardiology and Internal Medicine, Euro-Asian Respiratory Society, Bishkek, Kyrgyzstan, Department of Respiratory Medicine, University Hospital Olomouc, Olomouc, Czech Republic, Pulmonary Division, Heart Institute (InCor), Hospital da Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil, Department of Respiratory Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, Denmark, RNSA (Réseau National de Surveillance Aérobiologique), Brussieu, France, Sidkkids Hospitala and Institute of Health Policy, Management and Evaluation, Toronto, Canada, Department of ENT, Medical University of Graz, Graz, Austria, Pneumology and Allergy Department, CIBERES and Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, University of Barcelona, Barcelona, Spain, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria, NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation, Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russian Federation, Montevideo, Uruguay, Department of Public Health and Primary Care, Leiden University Medical Center (LUMC), Leiden, Netherlands, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, Netherlands, Department of Chest Medicine, Centre Hospitalier Universitaire UCL Namur, Université Catholique de Louvain, Yvoir, Belgium, Pulmonary Unit, Department of Medical Specialties, Arcispedale SMaria Nuova/IRCCS, AUSL di Reggio Emilia, Reggio Emilia, Italy, Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Pisa, Italy, CNR Institute of Biomedicine and Molecular Immunology A Monroy, Palermo, Italy, Nova Southeastern University, Fort Lauderdale, FL, United States, Dept. of Otorhinolaryngology, HNO-Klinik, Universitätsklinikum Düsseldorf, Düsseldorf, Germany, Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, Department of Medicine, Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada, Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States, Cyprus International Institute for Environmental, Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus, Department of Pediatrics, Hospital Archbishop Makarios III, Nicosia, Cyprus, Department of Pulmonary Diseases, Celal Bayar University, Faculty of Medicine, Manisa, Turkey, Allergy and Asthma Institute, Islamabad, Pakistan, Department of Paediatrics and Child Health, Red Cross Children's Hospital, Cape Town, South Africa, MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa, Bull DSAS, Echirolles, France, Universidad Católica de Córdoba, Córdoba, Argentina, Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing Institute of Otolaryngology, Beijing, China, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia, and National Hospital Organization, Tokyo National Hospital, Tokyo, Japan
Abstract: Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhi-nitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement. © The Author(s) 2019.
Published: 2019

23. MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence

Author: Bousquet, J. and Arnavielhe, S. and Bedbrook, A. and Bewick, M. and Laune, D. and Mathieu-dupas, E. and Murray, R. and Onorato, G.L. and Pépin, J.L. and Picard, R. and Portejoie, F. and Costa, E. and Fonseca, J. and Lourenço, O. and Morais-Almeida, M. and Todo-bom, A. and Cruz, A.A. and Silva, J.D. and Serpa, F.S. and Illario, M. and Menditto, E. and Cecchi, L. and Monti, R. and Napoli, L. and Ventura, M.T. and De Feo, G. and Larenas-linnemann, D. and Fuentes Perez, M. and Huerta Villabolos, Y.R. and Rivero-yeverino, D. and Rodriguez-zagal, E. and Amat, F. and Annesi-maesano, I. and Bosse, I. and Demoly, P. and Devillier, P. and Fontaine, J.F. and Just, J. and Kuna, T.P. and Samolinski, B. and Valiulis, A. and Emuzyte, R. and Kvedariene, V. and Ryan, D. and Sheikh, A. and Schmidt-grendelmeier, P. and Klimek, L. and Pfaar, O. and Bergmann, K.C. and Mösges, R. and Zuberbier, T. and Roller-wirnsberger, R.E. and Tomazic, P. and Fokkens, W.J. and Chavannes, N.H. and Reitsma, S. and Anto, J.M. and Cardona, V. and Dedeu, T. and Mullol, J. and Haahtela, T. and Salimäki, J. and Toppila-Salmi, S. and Valovirta, E. and Gemicioğlu, B. and Yorgancioglu, A. and Papadopoulos, N. and Prokopakis, E.P. and Bosnic-anticevich, S. and O’hehir, R. and Ivancevich, J.C. and Neffen, H. and Zernotti, E. and Kull, I. and Melen, E. and Wickman, M. and Bachert, C. and Hellings, P. and Palkonen, S. and Bindslev-jensen, C. and Eller, E. and Waserman, S. and Sova, M. and De Vries, G. and van Eerd, M. and Agache, I. and Casale, T. and Dykewickz, M. and Naclerio, R.N. and Okamoto, Y. and Wallace, D.V. and Hellings, P.W. and Aberer, W. and Akdis, C.A. and Akdis, M. and Alberti, M.R. and Almeida, R. and Angles, R. and Ansotegui, I.J. and Arnavielle, S. and Asayag, E. and Asarnoj, A. and Arshad, H. and Avolio, F. and Bacci, E. and Baiardini, I. and Barbara, C. and Barbagallo, M. and Baroni, I. and Barreto, B.A. and Basagana, X. and Bateman, E.D. and Bedolla-Barajas, M. and Beghé, B. and Bel, 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1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France, Euforea, Brussels, Belgium, KYomed-INNOV, Montpellier, France, iQ4U Consultants Ltd, London, United Kingdom, MedScript Ltd, Dundalk, Co Louth, Ireland, Laboratoire HP2, Grenoble, INSERM, U1042, Université Grenoble Alpes, Grenoble, France, CHU de Grenoble, Grenoble, France, Conseil Général de l’Economie Ministère de l’Economie, de l’Industrie et du Numérique, Paris, France, UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing, University of Porto (Porto4Ageing), Porto, Portugal, Center for Health Technology and Services Research, - CINTESIS, Faculdade de Medicina, Universidade do Porto, Porto, Portugal, Medida, Lda, Porto, Portugal, Faculty of Health Sciences and CICS – UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal, Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal, Imunoalergologia, Centro Hospitalar Universitário de Coimbra and Faculty of Medicine, University of Coimbra, Coimbra, Portugal, ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Vitória da Conquista, Brazil, WHO GARD Planning Group, Salvador, Brazil, Allergy Service, University Hospital of Federal University of Santa Catarina (HU-UFSC), Florianópolis, Brazil, Asthma Reference Center, Escola Superior de Ciencias da Santa Casa de Misericordia de Vitoria, Vitória, Esperito Santo, Brazil, Division for Health Innovation, Campania Region and Federico II University Hospital Naples (R&D and DISMET), Naples, Italy, CIRFF, Federico II University, Naples, Italy, SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy, Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, Torino, Italy, Consortium of Pharmacies and Services COSAFER, Salerno, Italy, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Salerno, Italy, Center of Excellence in Asthma and Allergy, Hospital Médica Sur, México City, Mexico, Mexico City, Mexico, Puebla, Puebla, Mexico, Ciutad Mexico, Mexico, Allergology Department, Centre de l’Asthme et des Allergies Hôpital d’Enfants Armand-Trousseau (APHP), Paris, France, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Universités, Equipe EPAR, Paris, 75013, France, Epidemiology of Allergic and Respiratory Diseases, Department Institute Pierre Louis of Epidemiology and Public Health, INSERM, UPMC Sorbonne Université, Medical School Saint Antoine, Paris, France, La Rochelle, France, Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France, UPRES EA220, Pôle des Maladies des Voies Respiratoires, Hôpital Foch, Université Paris-Saclay, Suresnes, France, Reims, France, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Clinic of Children’s Diseases, and Institute of Health Sciences Department of Public Health, Vilnius University Institute of Clinical Medicine, Vilnius, Lithuania, European Academy of Paediatrics (EAP/UEMS-SP), Brussels, Belgium, Clinic of Children’s Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Woodbrook Medical Centre, Loughborough, United Kingdom, Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Medical School, Edinburgh, United Kingdom, Centre of Medical Informatics, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom, Allergy Unit, Department of Dermatology, University Hospital of Zurich, Zürich, Switzerland, Center for Rhinology and Allergology, Wiesbaden, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Comprehensive Allergy, -Centre, -Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany, Global Allergy and Asthma European Network (GA2LEN), Berlin, Germany, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Cologne, Germany, CRI-Clinical Research International-Ltd, Hamburg, Germany, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Department of ENT, Medical University of Graz, Graz, Austria, Department of Otorhinolaryngology, Academic Medical Centre, Amsterdam, Netherlands, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands, ISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, IMIM (Hospital del Mar Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, Allergy Section, Department of Internal Medicine, Hospital Vall ‘dHebron & ARADyAL Research Network, Barcelona, Spain, AQuAS, Barcelona, Spain, EUREGHA, European Regional and Local Health Association, Brussels, Belgium, Rhinology Unit and Smell Clinic, ENT Department, Hospital Clínic, University of Barcelona, Barcelona, Spain, Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland, Association of Finnish Pharmacists, Helsinki, Finland, Department of Lung Diseases and Clinical Immunology, University of Turku, Turku, Finland, Terveystalo Allergy Clinic, Turku, Finland, Department of Pulmonary Diseases, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, Department of Pulmonary Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, GARD Executive Committee, Manisa, Turkey, Center for Pediatrics and Child Health, Institute of Human Development, Royal Manchester Children’s Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, 2nd Pediatric Clinic, Athens General Children’s Hospital 'P&A Kyriakou', University of Athens, Athens, 11527, Greece, Department of Otorhinolaryngology, University of Crete School of Medicine, Heraklion, Greece, Woolcock Institute of Medical Research, University of Sydney and Sydney Local Health District, Glebe, NSW, Australia, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia, Department of Immunology, Monash University, Melbourne, VIC, Australia, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Director of Center of Allergy, Immunology and Respiratory Diseases, Santa Fe, Argentina Center for Allergy and Immunology, Santa Fe, Argentina, Universidad Católica de Córdoba, Córdoba, Argentina, Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden, Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden, Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium, Department of Otorhinolaryngology, Univ Hospitals Leuven, Louvain, Belgium, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, EFA European Federation of Allergy and Airways Diseases Patients’ Associations, Brussels, Belgium, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Department of Medicine, Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada, University Hospital Olomouc, Olomouc, Czech Republic, Peercode BV, Geldermalsen, Netherlands, Faculty of Medicine, Transylvania University, Brasov, Romania, Division of Allergy/Immunology, University of South Florida, Tampa, United States, Section of Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, United States, Johns Hopkins School of Medicine, Baltimore, MD, United States, Department of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan, Nova Southeastern University, Fort Lauderdale, FL, United States, University Hospital, Montpellier, France, MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France, VIMA. INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium, Department of Dermatology, Medical University of Graz, Graz, Austria, Transylvania University Brasov, Brasov, Romania, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland, Chairman of the Council of Municipality of Salerno, Italy, Center for Health Technology and Services Research-CINTESIS, Faculdade de Medicina, Universidade do Porto, and Medida, Lda Porto, Portugal, Allergology department, Centre de l’Asthme et des Allergies Hôpital d’Enfants Armand-Trousseau (APHP), Sorbonne Université, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Equipe EPAR, Paris, France, Innovación y nuevas tecnologías, Salud Sector sanitario de Barbastro, Barbastro, Spain, Epidemiology of Allergic and Respiratory Diseases, Department Institute Pierre Louis of Epidemiology and Public Health, INSERM and Sorbonne Université, Medical School Saint Antoine, Paris, France, Department of Allergy and Immunology, Hospital Quirón Bizkaia, Erandio, Spain, KYomed INNOV, Montpellier, France, Argentine Society of Allergy and Immunopathology, Buenos Aires, Argentina, Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, and Astrid Lindgren Children’s Hospital, Department of Pediatric Pulmonology and Allergy, Karolinska University Hospital, Stockholm, Sweden, David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom, Regionie Puglia, Bari, Italy, Regione Liguria, Genoa, Italy, Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium, Allergy and Respiratory Diseases, Ospedale Policlinico San Martino, University of Genoa, Italy, PNDR, Portuguese National Programme for Respiratory Diseases, Faculdade de Medicina de Lisboa, Lisbon, Portugal, Director of the Geriatric Unit, Department of Internal Medicine (DIBIMIS), University of Palermo, Italy, Telbios SRL, Milan, Italy, Universidade do Estado do Pará, Belem, Brazil, Department of Medicine, University of Cape Town, Cape Town, South Africa, Hospital Civil de Guadalajara Dr Juan I Menchaca, Guadalarara, Mexico, Section of Respiratory Disease, Department of Oncology, Haematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy, Depart-ment of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Netherlands, Comprehensive Allergy Center Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Deptt of Respiratory Medicine, National Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh, Centre for Individualized Medicine, Department of Pediatrics, Faculty of Medicine, Linköping, Sweden, Depart-ment of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Poland, BIEBER. Department of Dermatology and Allergy, Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany, Dept of Biochemistry and Clinical Chemistry, Faculty of Pharmacy with the Division of Laboratory Medicine, Warsaw Medical University, Warsaw, Poland, Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden, Department of Geriatrics, Montpellier University Hospital, Montpellier, France, EA 2991, Euromov, University Montpellier, France, Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy, Argentine Association of Respiratory Medicine, Buenos Aires, Argentina, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Poland, Pediatric Department, University of Verona Hospital, Verona, Italy, Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy, Second University of Naples and Institute of Translational Medicine, Italian National Research Council, Italy, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and and Sydney Local Health District, Glebe, NSW, Australia, Allergist, La Rochelle, France, Associate professor of clinical medecine, Laval’s University, Quebec city, Head of medecine department, Hôpital de la MalbaieQC, Canada, Quebec Heart and Lung Institute, Laval University, Québec City, QC, Canada, Centre Hospitalier Valenciennes, France, Head of Department of Clinical Pharmacy of Lithuanian University of Health Sciences, Kaunas, Lithuania, Institute of Lung Health, Respiratory Biomedical Unit, University Hospitals of Leicester NHS Trust, Leicestershire, United Kingdom, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom, Department of Health Research Methods, Evidence and Impact, Division of Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, ON, Canada, Chief of the University Pneumology Unit-AOU Molinette, Hospital City of Health and Science of Torino, Italy, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany, Pharmacist, Municipality Pharmacy, Sarno, Italy, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania, Instituto de Pediatria, Hospital Zambrano Hellion Tec de Monterrey, Monterrey, Mexico, Imperial College and Royal Brompton Hospital, London, United Kingdom, Centro Medico Docente La Trinidad, CaRacas, Venezuela, Regional Director Assofarm Campania and Vice President of the Board of Directors of Cofaser, Salerno, Italy, Service de pneumologie, CHU et université d’Auvergne, Clermont-Ferrand, France, Department of Respiratory Diseases, Montpellier University Hospital, France, Imperial College London-National Heart and Lung Institute, Royal Brompton Hospital NHS, London, United Kingdom, Federal University of Minas Gerais, Medical School, Department of Pediatrics, Belo Horizonte, Brazil, Assitant Director General, Montpellier, Région Occitanie, France, Mayor of Sarno and President of Salerno Province, Director, Anesthesiology Service, Sarno 'Martiri del Villa Malta' Hospital, Italy, Allergy Section, Department of Internal Medicine, Hospital Vall d’Hebron & ARADyAL Spanish Research Network, Barcelona, Spain, Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway, CEDOC, Integrated Pathophysiological Mechanisms Research Group, Nova Medical School, Campo dos Martires da Patria, Lisbon, and Serviço de Imunoalergologia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal, Regional Ministry of Health of Andalusia, Seville, Spain, Allergy and Asthma Associates of Southern California, Mission Viejo, CA, United States, ASA-Advanced Solutions Accelerator, Clapiers, France, Division of Allergy/Immunology, University of South Florida, Tampa, FL, United States, Celentano pharmacy, Massa Lubrense, Italy, Allergy and Immunology Laboratory, Metropolitan University Hospital, Branquilla, Colombia, Capital Institute of Pediatrics, Chaoyang district, Beijing, China, School of Medicine, University CEU San Pablo, Madrid, Spain, David Tvildiani Medical University-AIETI Highest Medical School, David Tatishvili Medical Center Tbilisi, Georgia, Pulmonolory Research Institute FMBA, Moscow, Russian Federation, GARD Executive Committee, Moscow, Russian Federation, National Heart & Lung Institute, Imperial College, London, United Kingdom, Specialist social worker, Sorrento, Italy, Argentine Federation of Otorhinolaryngology Societies, Buenos Aires, Argentina, Eskisehir Osmangazi University, Medical Faculty, ENT Department, Eskisehir, Turkey, Medicine Department, IRCCS-Azienda Ospedaliera Universitaria San Martino, Genoa, Italy, Universidade Federal da Bahia, Escola de Enfermagem, Brazil, Plateforme Transversale d’Allergologie, Institut du Thorax, CHU de Nantes, Nantes, France, LANUA International Healthcare Consultancy, Northern Ireland, United Kingdom, Innovation and Research Office, Department of Health and Social Solidarity, Autonomous Province of Trento, Italy, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal, ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal, Guadalarara, Mexico, FIMMG (Federazione Italiana Medici di Medicina Generale), Milan, Italy, UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto(Porto4Ageing), Porto, Portugal, IMT Mines Alès, Unversité Montpellier, Alès, France, Department of Medicine, Nova Southeastern University, Davie, University of Miami Dept of Medicine, Miami, FL, United States, ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Planning Group, Brazil, Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, United Kingdom, Medical Consulting Czarlewski, Levallois, France, The Centre for Allergy Research, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Azienda Provinciale per i Servizi Sanitari di Trento (APSS-Trento), Italy, Department of Internal Medicine, Federal University of Santa Catarina, Trindade, Florianópolis, Santa Catarina, Brazil, Sleep Unit, Department of Neurology, Hôpital Gui-de-Chauliac Montpellier, Inserm U1061, France, Department of Dermatology and Allergy, Technische Universität München, Munich, Germany, ZAUM-Center for Allergy and Environment, Helmholtz Center Munich, Technische Universität München, Munich, Germany, Allergy Division, Chest Disease Department, University Hospital of Strasbourg, Strasbourg, France, AQuAS, Barcelna, Spain, Policlínica Geral do Rio de Janeiro, Rio de Janeiro, Brazil, Social workers oordinator, Sorrento, Italy, Federal University of the State of Rio de Janeiro, School of Medicine and Surgery, Rio de Janeiro, Brazil, Allergology and Immunology Discipline, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania, Department of Medicine, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, ON, Canada, Laboratoire de Pharmacologie Respiratoire UPRES EA220, Hôpital Foch, Suresnes, Université Versailles Saint-Quentin, Université Paris Saclay, France, Farmacie Dei Golfi Group, Massa Lubrense, Italy, Rangueil-Larrey Hospital, Respiratory Diseases Department, Toulouse, France, University Clinic of Pulmology and Allergy, Medical Faculty Skopje, North Macedonia, Service de Pneumo-Allergologie, Centre Hospitalo-Universitaire de Béni-Messous, Algiers, Algeria, Clinic of infectious, chest diseases, dermatology and allergology, Vilnius University, Vilnius, Lithuania, Allergy and Clinical Immunology National Heart and Lung Institute, Imperial College London, United Kingdom, Guy’s and st Thomas’ NHS Trust, Kings College London, United Kingdom, Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain Shams University, Cairo, Egypt, Department of Computing Science, Umeå University, Sweden and Four Computing Oy, Finland, University of São Paulo Medical School, Sao Paulo, Brazil, Andalusian Agency for Healthcare Quality, Seville, Spain, Global Allergy and Asthma Platform GAAPP, Vienna, Austria, Division of Allergy, Department of Pediatric Medicine-The Bambino Gesù Children’s Research Hospital Holy see, Rome, Italy, Department of Otorhinolaryngology, Amsterdam, University Medical Centres, AMC, Amsterdam, Netherlands, CINTESIS, Center for Research in Health Technologies and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, MEDIDA, Lda, Porto, Portugal, AllergistReims, France, Hospital general regional 1 'Dr Carlos Mc Gregor Sanchez Navarro' IMSS, Mexico City, Mexico, Regional hospital of ISSSTE, Puebla, Mexico, National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia, Allergy Clinic, National Institute of Respiratory Diseases, Mexico City, Mexico, Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istambul, Turkey, Allergology unit, UHATEM 'NIPirogov', Sofia, Bulgaria, Medical University, Faculty of Public Health, Sofia, Bulgaria, Allergy and Immunology Division, Clinica Ricardo Palma, Lima, Peru, Department of Internal Medicine, section of Allergology, Erasmus MC, Rotterdam, Netherlands, Allergy & Asthma Unit, Hospital San Bernardo Salta, Argentina, Allergy Clinic, Hospital Regional del ISSSTE ‘Lic. López Mateos’, Mexico City, Mexico, Centro Regional de Excelencia CONACYT y WAO en Alergia, Asma e Inmunologia, Hospital Universitario, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico, Center of Allergy and Immunology, Georgian Association of Allergology and Clinical Immunology, Tbilisi, Georgia, Latvian Association of Allergists, Center of Tuberculosis and Lung Diseases, Riga, Latvia, Federal District Base Hospital Institute, Brasília, Brazil, Institute of Health Policy and Management iBMG, Erasmus University, Rotterdam, Netherlands, University Hospital Olomouc – National eHealth Centre, Czech Republic, Immunology and Allergy Division, Clinical Hospital, University of Chile, Santiago, Chile, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland, Centich: centre d’expertise national des technologies de l’information et de la communication pour l’autonomie, Gérontopôle autonomie longévité des Pays de la Loire, Conseil régional des Pays de la Loire, Centre d’expertise Partenariat Européen d’Innovation pour un vieillissement actif et en bonne santé, Nantes, France, Autonomous University of Baja California, Ensenada, Baja California, Mexico, Department of Paediatrics and Child Health, University College Cork, Cork, Ireland, Hospital General Regional 1 'Dr. Carlos MacGregor Sánchez Navarro' IMSS, Mexico City, Mexico, Université Paris-Sud, Service de Pneumologie, Hôpital Bicêtre, Inserm UMR_S999, Le Kremlin Bicêtre, France, Dipartimento di medicina, chirurgia e odontoiatria, università di Salerno, Italy, Division for Health Innovation, Campania Region and Federico II University Hospital Naples (R&D and DISMET) Naples, Italy, Libra Foundation, Buenos Aires, Argentina, Medical University of Gdańsk, Department of Allergology, Gdansk, Poland, Airway Disease Infection Section, National Heart and Lung Institute, Imperial College, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom, Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, Hallym University College of Medicine, Hallym University Sacred Heart HospitalGyeonggi-do, South Korea, Department of Clinical Immunology, Wrocław Medical University, Poland, Ukrainina Medical Stomatological Academy, Poltava, Ukraine, Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey, Hacettepe University, School of Medicine, Department of Chest Diseases, Immunology and Allergy Division, Ankara, Turkey, Allergy Centre, Tampere University Hospital, Tampere, Finland, First Department of Family Medicine, Medical University of Lodz, Poland, Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, and Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Germany, Department of Medicine, McMaster University, HealthSciences Centre 3V47, West, Hamilton, ON, Canada, National Research Center, Institute of Immunology, Federal Medicobiological Agency, Laboratory of Molecular immunology, Moscow, Russian Federation, GARD Chairman, Geneva, Switzerland, Allergy & Asthma Center Westend, Berlin, Germany, Department of Immunology and Allergy, Healthy Ageing Research Center, Medical University of Lodz, Lodz, Poland, Children’s Hospital and University of Helsinki, Finland, Department of Prevention of Envinronmental Hazards and Allergology, Medical University of Warsaw, Poland, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Presidente CMMC, Milano, Italy, Head of the Allergy Department of Pedro de Elizalde Children’s Hospital, Buenos Aires, Argentina, University of Medicine and Pharmacy, Hochiminh City, Viet Nam, Federal University of Bahia, Brazil, Sifmed, Milano, Italy, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, Departments of Internal Medicine and Pediatrics (Divisions of Allergy and Immunology), University of Tennessee College of Medicine, Germantown, TN, United States, Scottish Centre for Respiratory Research, Cardiovascular & Diabetes Medicine, Medical Research Institute, Ninewells Hospital, University of Dundee, United Kingdom, Oslo University Hospital, Department of Paediatrics, Oslo, and University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, Oslo, Norway, Department of Pulmonary Medicine, CHU Sart-Tilman, and GIGA I3 research group, Liege, Belgium, Department of Philosophical, Methodological and Instrumental Disciplines, CUCS, University of Guadalajara, Guadalajara, Mexico, Department of Pulmonary Medicine, Rashid Hospital, Dubai, United Arab Emirates, Biomax Informatics AG, Munich, Germany, Director Gerneral for Health and Social Care, Scottish Government, Edinburgh, United Kingdom, Department of Respiratory Medicine, University of Bratislava, Bratislava, Slovakia, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal, Ageing@Coimbra EIP-AHA Reference Site, Coimbra, Portugal, Medical center Iskar Ltd Sofia, Bulgaria, Department of Medicine (RCSI), Bon Secours Hospital, Glasnevin, Dublin, Ireland, Kronikgune, International Centre of Excellence in Chronicity Research Barakaldo, Bizkaia, Spain, Division of Clinical Immunology and Allergy, Laboratory of Behavioral Immunology Research, The University of Mississippi Medical Center, Jackson, MS, United States, Tobacco Control Research Centre, Iranian Anti Tobacco Association, Tehran, Iran, Argentine Association of Allergy and Clinical Immunology, Buenos Aires, Argentina, University of Southeast Bahia, Brazil, Allergie-Centrum-Charité at the Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Germany, Maputo Central Hospital--Department of Paediatrics, Mozambique, Veracruz, Mexico, Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Allergy and Asthma Medical Group and Research Center, San Diego, CA, United States, Department of Physiology, CHRU, University Montpellier, Vice President for Research, PhyMedExp, INSERM U1046, CNRS UMR 9214, France, Croatian Pulmonary Society, Croatia, National Institute of Pneumology M Nasta, Bucharest, Romania, Clinic for Pulmonary Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbian Association for Asthma and COPD, Belgrade, Serbia, Regione Piemonte, Torino, Italy, Col Jardines de Sta Monica, Tlalnepantla, Mexico, National Center for Research in Chronic Respiratory Diseases, Tishreen University School of Medicine, Latakia, Syrian Arab Republic, Department of Public health and health products, Paris Descartes University-Sorbonne Paris Cité, EA 4064 and Paris Municipal Department of social action, childhood, and health, Paris, France, Paris municipal Department of social action, childhood, and health, Paris, France, Lead Respiratory Physician Mater Dei Hospital Malta, Academic Head of Dept and Professor of Medicine University of Malta, Deputy Dean Faculty of Medicine and Surgery University of Medicine, La Valette, Malta, Instituto de Prevision Social IPS HC, Socia de la SPAAI, Tesorera de la SLAAI, Asuncion, Paraguay, Universidade de São Paulo, São Paulo, Brazil, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Germany and CRI-Clinical Research International-Ltd, Hamburg, Germany, General Pathology Institute, Faculty of Medicine, University of Coimbra, Portugal, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Spain, Danish Commitee for Health Education, Copenhagen East, Denmark, Food Allergy Referral Centre Veneto Region, Department of Women and Child Health, Padua General University Hospital, Padua, Italy, Medical Communications Consultant, MedScript Ltd, Dundalk, Co Louth, Ireland and Honorary Research Fellow, OPC, Cambridge, United Kingdom, General Manager of COFASER-Pharmacy Services Consortium, Salerno, Italy, Scientific Centre of Children’s Health under the MoH, Moscow, Russian National Research Medical University named Pirogov, Moscow, Russian Federation, Dept of Otorhinolaryngology, Medical University of Vienna, AKH, Vienna, Austria, Hospital of the Hospitaller Brothers in Buda, Budapest, Hungary, Die Hautambulanz and Rothhaar study center, Berlin, Germany, Neumología y Alergología Infantil, Hospital La Fe, Valencia, Spain, Center for Health Technology and Services Research-CINTESIS and Department of Internal Medicine, Centro Hospitalar Sao Joao, Porto, Portugal, Caisse d’assurance retraite et de la santé au travail du Languedoc-Roussillon (CARSAT-LR), Montpellier, France, Director of Department of Pharmacy of University of Naples Federico II, Naples, Italy, ENT Department, University Hospital of Kinshasa, Kinshasa, Congo, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia, Medical center 'Research expert', Varna, Bulgaria, National Hospital Organization, Tokyo National Hospital, Tokyo, Japan, Dept of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan, Dept of Otolaryngology, Nippon Medical School, Tokyo, Japan, Jalisco, Guadalarara, Mexico, Centre Hospitalier Universitaire Pédiatrique Charles de Gaulle, Ouagadougou, Burkina Faso, Dept of Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine and Medical University, Vienna, Austria, Department of Immunology and Allergology, Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children’s Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, 2nd Pediatric Clinic, Athens General Children’s Hospital 'P&A Kyriakou,' University of Athens, Athens, Greece, Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea, Respiratory Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy, Allergy and Respiratory Diseases, Ospedale Policlino San Martino-University of Genoa, Italy, Farmacias Holon, Lisbon, Portugal, Department of Pediatrics, Nippon Medical School, Tokyo, Japan, University of Southern Denmark, Kolding, Denmark, Université Grenoble Alpes, Laboratoire HP2, Grenoble, INSERM, U1042 and CHU de Grenoble, France, Allergy Unit, CUF-Porto Hospital and Institute, Center for Research in Health Technologies and information systems CINTESIS, Universidade do Porto, Portugal, Sociologist, municipality area n33, Sorrento, Italy, Centre for empowering people and communites, Dublin, United Kingdom, Société de Pneumologie de Langue Française, Espace francophone de Pneumologie, Paris, France, Département de pédiatrie, CHU de Grenoble, Grenoble, France, Medical School, University of Cyprus, Nicosia, Cyprus, Children’s Hospital Srebrnjak, Zagreb, School of Medicine, University J.J. Strossmayer, Osijek, Croatia, Karl Landsteiner Institute for Clinical and Experimental Pneumology, Hietzing Hospital, Vienna, Austria, University Hospital ‘Sv. Ivan Rilski’', Sofia, Bulgaria, Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, Cape Town, South Africa, IML, Milano, Italy, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom, Observational and Pragmatic Research Institute, Singapore, Singapore, Department of Otorhinolaryngology University of Crete School of Medicine, Heraklion, Greece, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Brussels, Belgium, Cancun, Quintana Roo, Mexico, LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany, Department of Medicine, Christian Albrechts University, Airway Research Center North, Member of the German Center for Lung Research (DZL), Kiel, Germany, Department of Nephrology and Endocrinology, Karolinska University Hospital, Stockholm, Sweden, Farmácia São Paio, Vila Nova de Gaia, Porto, Portugal, St Vincent’s Hospital and University of Sydney, Sydney, NSW, Australia, Puebla, Mexico, Serviço de Pneumologia-Hosp das Clinicas UFPE-EBSERH, Recife, Brazil, Universidade Federal de São Paulo, São Paulo, Brazil, Centre of Pneumology, Coimbra University Hospital, Portugal, Polibienestar Research Institute, University of Valencia, Valencia, Spain, Pediatric Allergy and Clinical Immunology, Hospital Angeles Pedregal, Mexico City, Mexico, Getafe University Hospital Department of Geriatrics, Madrid, Spain, Association Asthme et Allergie, Paris, France, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, Primary Care Respiratory Research Unit Institutode Investigación Sanitaria de Palma IdisPa, Palma de Mallorca, Spain, Allergy Unit, Presidio Columbus, Rome, Catholic University of Sacred Heart, Rome and IRCCS Oasi Maria SS, Troina, Italy, Medical University of Graz, Department of Internal Medicine, Graz, Austria, Serviço de Imunoalergologia Hospital da Luz Lisboa, Portugal, Hospital de Clinicas, University of Parana, Brazil, Division of Allergy Asthma and Clinical Immunology, Emek Medical Center, Afula, Israel, Honorary Clinical Research Fellow, Allergy and Respiratory Research Group, The University of Edinburgh, Edinburgh, United Kingdom, Showa University School of Medicine, Tokyo, Japan, Association of Finnish Pharmacies, Finland, Allergy and Clinical Immunology Department, Centro Médico-Docente la, Trinidad and Clínica El Avila, Caracas, Venezuela, Faculty of Medicine, Autnonous University of Madrid, Spain, The Royal National TNE Hospital, University College London, United Kingdom, DIBIMIS, University of Palermo, Italy, Asthma Reference Center, Escola Superior de Ciencias da Santa Casa de Misericordia de Vitoria-Esperito Santo, Brazil, THe Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom, Department of Pediatrics & Child Health, Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada, INSERM, Université Grenoble Alpes, IAB, U 1209, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Université Joseph Fourier, Grenoble, France, Sociedad Paraguaya de Alergia Asma e Inmunologı´a, Paraguay, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil, European Health Futures Forum (EHFF), Dromahair, Ireland, ENT, Aachen, Germany, Kyrgyzstan National Centre of Cardiology and Internal medicine, Euro-Asian respiratory Society, Bishkek, Kyrgyzstan, University Hospital Olomouc, Czech Republic, Department of Paediatric and Adolescent medicine, University Hospital of North Norway, Tromsø, Paediatric Research Group, Deptarment of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway, Presidente, IML (Lombardy Medical Initiative), Bergamo, Italy, Pulmonary Division, Heart Institute (InCor), Hospital da Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil, Public Health Institute of Vilnius University, Vilnius, Lithuania, Universi-dade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, RNSA (Réseau National de Surveillance Aérobiologique), Brussieu, France, The Hospital for Sick Children, Dalla Lana School of Public Health, University of Toronto, Canada, Imunoalergologia, Centro Hospitalar Universitário de Coimbra and Faculty of Medicine, University of Coimbra, Portugal, Depart-ment of ENT, Medical University of Graz, Austria, Campania Region, Division on Pharmacy and devices policy, Naples, Italy, Department of Respiratory Medicine, Hvidovre Hospital & University of Copenhagen, Denmark, Universidade Federal dos Pampas, Uruguaiana, Brazil, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria, Pneumology and Allergy Department CIBERES and Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, University of Barcelona, Spain, Vilnius University Institute of Clinical Medicine, Clinic of Children’s Diseases, and Institute of Health Sciences, Department of Public Health, Vilnius, Lithuania, Department of Lung Diseases and Clinical Immunology Allergology, University of Turku and Terveystalo allergy clinic, Turku, Finland, PELyon, HESPER 7425, Health Services and Performance Resarch-Université Claude Bernard Lyon, France, Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden, Department of Chest Medicine, Centre Hospitalier Universitaire UCL Namur, Université Catholique de Louvain, Yvoir, Belgium, University of Bari Medical School, Unit of Geriatric Immunoallergology, Bari, Italy, Pulmonary Unit, Department of Medical Specialties, Arcispedale SMaria Nuova/IRCCS, AUSL di Reggio Emilia, Italy, FILHA, Finnish Lung Association, Helsinki, Finland, Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Pisa, Italy, CNR Institute of Biomedicine and Molecular Immunology 'A Monroy', Palermo, Italy, Medical University, Plovdiv, Bulgaria, Department of Otorhinolaryngology, Plovdiv, Bulgaria, Sotiria Hospital, Athens, Greece, Dept of Otorhinolaryngology, Universitätsklinikum Düsseldorf, Germany, Asthma UK, Mansell street, London, United Kingdom, Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany, Department of Medicine Solna, Immunology and Allergy Unit, Karolinska Institutet and Department of ENT diseases, Karolinska University Hospital, Stockholm, Sweden, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States, International Primary Care Respiratory Group IPCRG, Aberdeen, United Kingdom, Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom, Allergologyst-Medical College of Medical Faculty, Thracian University, Stara Zagora, Bulgaria, Department of Research, Olmsted Medical Center, Rochester, MN, United States, Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus, Department of Pediatrics, Hospital 'Archbishop Makarios III', Nicosia, Cyprus, Celal Bayar University Department of Pulmonology, Manisa, Turkey, The Allergy and Asthma Institute, Pakistan, Department of Paediatrics and Child Health, Red Cross Children’s Hospital, and MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa, Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital and Beijing Institute of Otolaryngology, Beijing, China, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia, Gesundheitsregion KölnBonn-HRCB Projekt GmbH, Kohln, Germany, and Akershus University Hospital, Department of Otorhinolaryngology, Akershus, Norway
Abstract: mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary. © 2018 The Author(s).
Published: 2018

24. Loss of TLR3 aggravates CHIKV replication and pathology due to an altered virus-specific neutralizing antibody response

Author: Lisa F. P. Ng, Yee Sin Leo, Jeslin J. L. Tan, Teck-Hui Teo, Angela Chow, Zhisheng Her, Valeria Lulla, Subhra K. Biswas, Aleksei Lulla, Terk-Shin Teng, Rossella Melchiotti, Wendy W. L. Lee, Mar Kyaw Win, Anand Kumar Andiappan, Marc Lecuit, Laurent Rénia, Fok-Moon Lum, Andres Merits, Christelle Gabriel, Yiu-Wing Kam, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Yong Loo Lin School of Medicine [Singapore], National University of Singapore (NUS), Dipartimento di Informatica, Matematica, Elettronica e Trasporti [Reggio Calabria] (DIMET), Universita Mediterranea of Reggio Calabria [Reggio Calabria], University of Tartu, Tan Tock Seng Hospital, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institute of Infection and Global Health [University of Liverpool, UK], University of Liverpool, This research was funded by SIgN, A*STAR and supported by the Biomedical Research Council, A*STAR, and European Union FP7 project ‘Integrated Chikungunya Research’ (ICRES, Grant no. 261202). Zhisheng Her and Fok‐Moon Lum are supported by the President's Graduate Fellowship from the Yong Loo Lin School of Medicine, National University of Singapore. Teck‐Hui Teo is supported by the A*STAR postgraduate scholarship. Wendy W.L. Lee is supported by the postgraduate scholarship from the NUS Graduate School for Integrative Science and Engineering., We thank Jean‐Laurent Casanova and his team (Shen‐Ying Zhang, Vanessa Sancho‐Shimizu, Michael J. Ciancanelli) from Rockefeller University for providing the human primary TRIF−/− fibroblasts. We thank Anis Larbi and the SIgN Flow Cytometry core for assistance with cytometry analysis. We are grateful to Michael Poidinger for assistance with genotyping analysis and to Ruo‐Yan Ong, Irina Shalova and Hong‐Rong Loh from SIgN for technical assistance. We also thank the Advanced Molecular Pathology Laboratory (IMCB, A*STAR) for performing the histology work. We acknowledge Kai‐Er Eng from SIgN and Lucy Robinson of Insight Editing London for assistance with manuscript editing., European Project: 261202,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,ICRES(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Yong Loo Lin School of Medicine, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], and Institut des Maladies Génétiques Imagine [Paris]
Subjects: Male, Pathology, viruses, [SDV]Life Sciences [q-bio], MESH: Chikungunya Fever, Antibodies, Viral, Virus Replication, medicine.disease_cause, MESH: Mice, Knockout, MESH: Antibodies, Neutralizing, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, TLR3 Subject Categories Immunology, MESH: Animals, Chikungunya, TLR3, Neutralizing antibody, innate immunity, Research Articles, Mice, Knockout, MESH: Aged, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, biology, MESH: Polymorphism, Single Nucleotide, virus diseases, hemic and immune systems, Middle Aged, MESH: Toll-Like Receptor 3, 3. Good health, medicine.anatomical_structure, MESH: Young Adult, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Chikungunya virus, Adult, medicine.medical_specialty, chemical and pharmacologic phenomena, Polymorphism, Single Nucleotide, Microbiology, Virus, Young Adult, 03 medical and health sciences, Species Specificity, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, MESH: Species Specificity, neutralizing antibodies, MESH: Mice, Aged, 030304 developmental biology, Innate immune system, MESH: Humans, MESH: Virus Replication, MESH: Adult, MESH: Chikungunya virus, Antibodies, Neutralizing, Virology, MESH: Male, Toll-Like Receptor 3, Mice, Inbred C57BL, Virology & Host Pathogen Interaction, joint inflammation, Viral replication, Immunology, biology.protein, Chikungunya Fever, Bone marrow, MESH: Female, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; RNA-sensing toll-like receptors (TLRs) mediate innate immunity and regulate anti-viral response. We show here that TLR3 regulates host immunity and the loss of TLR3 aggravates pathology in Chikungunya virus (CHIKV) infection. Susceptibility to CHIKV infection is markedly increased in human and mouse fibroblasts with defective TLR3 signaling. Up to 100-fold increase in CHIKV load was observed in Tlr3 À/À mice, alongside increased virus dissemination and pro-inflammatory myeloid cells infiltration. Infection in bone marrow chimeric mice showed that TLR3-expressing hemato-poietic cells are required for effective CHIKV clearance. CHIKV-specific antibodies from Tlr3 À/À mice exhibited significantly lower in vitro neutralization capacity, due to altered virus-neutralizing epitope specificity. Finally, SNP genotyping analysis of CHIKF patients on TLR3 identified SNP rs6552950 to be associated with disease severity and CHIKV-specific neutralizing antibody response. These results demonstrate a key role for TLR3-mediated antibody response to CHIKV infection, virus replication and pathology, providing a basis for future development of immunotherapeutics in vaccine development.
Published: 2014
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25. Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells

Author: Valerie Chun Ling Lin, Natasa Bajalovic, Esther Wong, Sijie Tan, School of Biological Sciences, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: Transcriptional Activation, 0301 basic medicine, Progesterone receptor B, Breast Neoplasms, Adenocarcinoma, Biology, Promegestone, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Protein Interaction Mapping, Breast Cancer, Progesterone receptor, Gene expression, Autophagy, Humans, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Autophagosomes, Biological sciences [Science], Cell Biology, Recombinant Proteins, Neoplasm Proteins, Cell biology, Gene Expression Regulation, Neoplastic, Protein Transport, 030104 developmental biology, MCF-7, 030220 oncology & carcinogenesis, Cancer cell, MCF-7 Cells, TFEB, Female, Lysosomes, Receptors, Progesterone, Microtubule-Associated Proteins, Nuclear localization sequence, Signal Transduction
Abstract: Autophagy is an evolutionary conserved, self-eating process that targets cellular constituents for lysosomal degradation. Transcription factor EB (TFEB) is a master regulator of autophagy by inducing the expression of genes involved in autophagic and lysosomal degradation. In breast cancer, ligand-activated progesterone receptor has been reported to influence cancer development by manipulating the autophagy pathway. However, understanding of the mechanism that underlies this autophagic response remains limited. Herein, we report that prolonged treatment with progestin R5020 upregulates autophagy in MCF-7 human breast cancer cells via a novel interplay between progesterone receptor B (PRB) and TFEB. R5020 upregulates TFEB gene expression and protein levels in a PRB-dependent manner. Additionally, R5020 enhances the co-recruitment of PRB and TFEB to each other to facilitate TFEB nuclear localization. Once in the nucleus, TFEB induces the expression of autophagy and lysosomal genes to potentiate autophagy. Together, our findings highlight a novel functional connection between ligand-activated PRB and TFEB to modulate autophagy in MCF-7 breast cancer cells. As breast cancer development is controlled by autophagy, the progestin-PRB-TFEB transduction pathway warrants future attention as a potential therapeutic target in cancer therapy. Ministry of Education (MOE) This work is supported by Singapore Ministry of Education Academic Research Fund Tier 2, MOE2014-T2-2-125.
Published: 2019
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26. Mechanical confinement triggers glioma linear migration dependent on formin FHOD3

Author: Yuk Kien Chong, Anitha Krishnasamy, Carol Tang, Benoit Ladoux, Evelyn K.F. Yim, Nils C. Gauthier, Wai Hoe Ng, Beng Ti Ang, Sharvari R. Sathe, Charlotte Guetta-Terrier, Pascale Monzo, Michael P. Sheetz, Mechanobiology Institute [Singapore] (MBI), National University of Singapore (NUS), National Neuroscience Institute, National University Health System, Department of Surgery [Singapore], National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Department of Biomedical Engineering Singapore, National Neuroscience Institute of Singapore, Duke-NUS Medical School [Singapore], Yong Loo Lin School of Medicine, National University of Singapore, Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Mechanobiology Institute, National University of Singapore, National Institutes of Health through Columbia University, and Duke-NUS Graduate Medical School Singapore
Subjects: 0301 basic medicine, Formins, Muscle Proteins, Motility, Cell Count, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Actin-Related Protein 2-3 Complex, 03 medical and health sciences, Cell Movement, Laminin, Glioma, Cell Adhesion, Tumor Cells, Cultured, medicine, Animals, Humans, Cell adhesion, Molecular Biology, Actin, Paxillin, ComputingMilieux_MISCELLANEOUS, Brain Neoplasms, fungi, Microfilament Proteins, Articles, Cell Biology, Anatomy, medicine.disease, Biomechanical Phenomena, Rats, Cell Motility, 030104 developmental biology, biology.protein, Biophysics, MDia1, Cell Migration Assays, Glioblastoma
Abstract: Glioma linear migration on brain blood vessels is recapitulated in vitro. This migration is characterized by a two-phase process activated by laminin, confinement, and linear topology. It requires a unique balance of actin polymerization systems emphasizing formins and not Arp2/3 and is a powerful tool for identifying new targets such as the formin FHOD3., Glioblastomas are extremely aggressive brain tumors with highly invasive properties. Brain linear tracks such as blood vessel walls constitute their main invasive routes. Here we analyze rat C6 and patient-derived glioma cell motility in vitro using micropatterned linear tracks to mimic blood vessels. On laminin-coated tracks (3–10 μm), these cells used an efficient saltatory mode of migration similar to their in vivo migration. This saltatory migration was also observed on larger tracks (50–400 μm in width) at high cell densities. In these cases, the mechanical constraints imposed by neighboring cells triggered this efficient mode of migration, resulting in the formation of remarkable antiparallel streams of cells along the tracks. This motility involved microtubule-dependent polarization, contractile actin bundles and dynamic paxillin-containing adhesions in the leading process and in the tail. Glioma linear migration was dramatically reduced by inhibiting formins but, surprisingly, accelerated by inhibiting Arp2/3. Protein expression and phenotypic analysis indicated that the formin FHOD3 played a role in this motility but not mDia1 or mDia2. We propose that glioma migration under confinement on laminin relies on formins, including FHOD3, but not Arp2/3 and that the low level of adhesion allows rapid antiparallel migration.
Published: 2016
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27. Ontological coaching among nursing undergraduates: a pilot randomized controlled (OCEAN) trial.

Author: Pereira TL, Ang E, Aayisha, Naidu KNC, Chan YH, and Shorey S
Subjects: Humans, Pilot Projects, Female, Male, Education, Nursing, Baccalaureate, Young Adult, Resilience, Psychological, Goals, Adult, Interviews as Topic, Mentoring, Students, Nursing psychology, Social Support
Abstract: To develop and assess the preliminary effectiveness of Ontological Coaching Intervention for nursing undergraduates. Design: A pilot randomized controlled trial with a two-group pre-test and post-test followed by process-evaluation qualitative interviews. An Ontological Coaching Intervention was developed through an integration of prior literature and the collective the research team's experience, consisting of 4-6 sessions over 6-months, each lasting 30-60 minutes. Sessions encompassed exploring ontological coaching concepts, empowering nursing undergraduates to choose topics, and tailoring sessions to individual needs. Sixty undergraduates were recruited; ten were excluded for not completing the baseline questionnaires. Twenty-one nursing undergraduates were randomly assigned to the intervention group and twenty-nine undergraduates to the control group (standard academic support only). Primary (psychological well-being) and secondary (social support quantity and satisfaction, goal-setting, resilience) outcomes were measured at baseline, 3-months, and 6-months. Semi-structured interviews captured post-intervention experiences. Between-group analyses revealed a significant difference in goal-setting scores at 3-months (U = 325.5, p = 0.013), favoring the intervention group (median = 70.50, IQR = 64.25, 76.75). At 6-months, a significant difference in social support satisfaction scores (U = 114.5, p = 0.028) was found between the intervention (median = 33.00, IQR = 29.50, 35.25) and control (median = 30.00, IQR = 30.00, 35.00) groups. However, no significant between-group differences were noted in other outcome measures. Significant within-group differences were found in goal-setting scores at 3- and 6-months in the intervention group and social support quantity scores at 3- and 6-months in the control group. However, no significant within-group differences were noted in other outcome measures. Three themes were identified: Enhanced Holistic Development, Keys to Successful Coaching, and Future Directions for Successful Coaching. There is urgent need to advance research on Ontological Coaching Intervention, particularly, enhancing study rigor, broadening examinations to diverse healthcare student populations and cultural contexts, and addressing identified limitations.
Published: 2024
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28. Prediction and Management of Small-for-Size Syndrome in Living Donor Liver Transplantation.

Author: Law JH and Kow AW
Abstract: Small-for-Size Syndrome (SFSS) remains a critical challenge in living donor liver transplantation (LDLT), characterized by graft insufficiency due to inadequate liver volume, leading to significant postoperative morbidity and mortality. As the global adoption of LDLT increases, the ability to predict and manage SFSS has become paramount in optimizing recipient outcomes. This review provides a comprehensive examination of the pathophysiology, risk factors, and strategies for managing SFSS across the pre-, intra-, and postoperative phases. The pathophysiology of SFSS has evolved from being solely volume-based to incorporating portal hemodynamics, now recognized as Small-for-Flow Syndrome. Key risk factors include donor-related parameters like age and graft volume, recipient-related factors such as MELD score and portal hypertension, and intraoperative factors related to venous outflow and portal inflow modulation. Current strategies to mitigate SFSS include careful graft selection based on graft-to-recipient weight ratio and liver volumetry, surgical techniques to optimize portal hemodynamics, and novel interventions such as splenic artery ligation and hemiportocaval shunts. Pharmacological agents like somatostatin and terlipressin have also shown promise in modulating portal pressure. Advances in 3D imaging and artificial intelligence-based volumetry further aid in preoperative planning. This review emphasizes the importance of a multifaceted approach to prevent and manage SFSS, advocating for standardized definitions and grading systems. Through an integrated approach to surgical techniques, hemodynamic monitoring, and perioperative management, significant strides can be made in improving the outcomes of LDLT recipients. Further research is necessary to refine these strategies and expand the application of LDLT, especially in challenging cases involving small-for-size grafts.
Published: 2024
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29. Detecting a wide range of epitranscriptomic modifications using a nanopore-sequencing-based computational approach with 1D score-clustering.

Author: Vujaklija I, Biđin S, Volarić M, Bakić S, Li Z, Foo R, Liu J, and Šikić M
Abstract: To date, over 40 epigenetic and 300 epitranscriptomic modifications have been identified. However, current short-read sequencing-based experimental methods can detect <10% of these modifications. Integrating long-read sequencing technologies with advanced computational approaches, including statistical analysis and machine learning, offers a promising new frontier to address this challenge. While supervised machine learning methods have achieved some success, their usefulness is restricted to a limited number of well-characterized modifications. Here, we introduce Modena, an innovative unsupervised learning approach utilizing long-read nanopore sequencing capable of detecting a broad range of modifications. Modena outperformed other methods in five out of six benchmark datasets, in some cases by a wide margin, while being equally competitive with the second best method on one dataset. Uniquely, Modena also demonstrates consistent accuracy on a DNA dataset, distinguishing it from other approaches. A key feature of Modena is its use of 'dynamic thresholding', an approach based on 1D score-clustering. This methodology differs substantially from the traditional statistics-based 'hard-thresholds.' We show that this approach is not limited to Modena but has broader applicability. Specifically, when combined with two existing algorithms, 'dynamic thresholding' significantly enhances their performance, resulting in up to a threefold improvement in F1-scores., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Published: 2024
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30. Comparison of safety and immunogenicity in the elderly after receiving either Comirnaty or Spikevax monovalent XBB1.5 COVID-19 vaccine.

Author: Mok CKP, Tang YS, Tan CW, Chong KC, Chen C, Sun Y, Yiu K, Ling KC, Chan KK, and Hui DS
Abstract: Background: The emergence of SARS-CoV-2 variants necessitates ongoing evaluation of vaccine performance. This study evaluates and compares the safety and immunogenicity of the Comirnaty and Spikevax monovalent XBB.1.5 COVID-19 vaccines in an elderly population., Methods: Altogether 129 elderly individuals were recruited between 2 January and 3 February 2024, and received a booster dose of either Comirnaty (n=59) or Spikevax (n=70) monovalent XBB.1.5 COVID-19 vaccine. Blood samples were collected at before and one month after vaccination. Immunogenicity was assessed by measuring the percentage of IFNγ + CD4 + and IFNγ + CD8 + T cells, and neutralizing antibody titers (NT50) using a surrogate virus neutralization test (sVNT). Adverse reactions were recorded and analyzed., Findings: Both vaccines significantly increased the percentage of IFNγ + CD8 + T cells against XBB.1.5 and wild-type (WT) SARS-CoV-2 at one-month post-vaccination. Spikevax induced a significantly higher percentages of IFNγ + CD8 + and CD4 + T cells against XBB.1.5 than Comirnaty (p<0.001). The proportion of participants showing a positive T cell response to XBB1.5 after vaccination was higher in the Spikevax group (64.3% CD8, 71.4% CD4) than the Comirnaty group (42.4% CD8, 57.6% CD4). Spikevax also elicited higher NT50 levels against XBB1.5, JN.1 and the latest variant KP.2 than Comirnaty (XBB1.5: p<0.01; KP.2: p<0.05). Fever was more common in the Spikevax group (fever: p=0.006). However, all side effects were short-term and resolved on their own., Interpretation: Both vaccines induce neutralizing antibody to XBB1.5, JN.1 and KP.2. Specifically, Spikevax induces higher cellular and humoral immune responses than Comirnaty in the elderly, but it is also associated with a higher incidence of fever. These findings can guide public health strategies for vaccinating the elderly population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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31. Metabolomics at the cutting edge of risk prediction of MASLD.

Author: Tan EY, Muthiah MD, and Sanyal AJ
Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health threat globally. Management of patients afflicted with MASLD and research in this domain are limited by the lack of robust well-established non-invasive biomarkers for diagnosis, prognostication, and monitoring. The circulating metabolome reflects both the systemic metabo-inflammatory milieu and changes in the liver in affected individuals. In this review we summarize the available literature on changes in the different components of the metabolome in MASLD with a focus on changes that are linked to the presence of underlying steatohepatitis, severity of disease activity, and fibrosis stage. We further summarize the existing literature around biomarker panels that are derived from interrogation of the metabolome. Their relevance to disease biology and utility in practice are also discussed. We further highlight potential direction for future studies particularly to ensure they are fit for purpose and suitable for widespread use., Competing Interests: Declaration of interests M.D.M. has served as a consultant or on advisory board for Roche, Astellas, Gilead, and Lerna Biopharma and has received honoraria for lectures from Boston Scientific, Olympus Medical, Roche, and Astellas. A.J.S. has served as a consultant to 89Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, Eli Lilly, Histoindex, Janssen, Lipocine, Madrigal, Merck, Glaxo-Smith Kline, Novartis, Akero, Novo Nordisk, Path AI, Histoindex, Pfizer, Poxel, Salix, Myovant, Sequana, Surrozen, Takeda, Terns, and Zydus; his institution has received grant support from AstraZeneca, Bristol-Myers Squibb, Gilead, Intercept, Mallinckrodt, Merck, Ocelot, and Salix; he receives royalties from Elsevier and UpToDate and has stock options in Durect, Genfit, Tiziana, and Inversago., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2024
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32. Disagreement on foundational principles of biological aging.

Author: Gladyshev VN, Anderson B, Barlit H, Barré B, Beck S, Behrouz B, Belsky DW, Chaix A, Chamoli M, Chen BH, Cheng K, Chuprin J, Churchill GA, Cipriano A, Colville A, Deelen J, Deigin Y, Edmonds KK, English BW, Fang R, Florea M, Gershteyn IM, Gill D, Goetz LH, Gorbunova V, Griffin PT, Horvath S, Borch Jensen M, Jin X, Jovanovska S, Kajderowicz KM, Kasahara T, Kerepesi C, Kulkarni S, Labunskyy VM, Levine ME, Libert S, Lu JY, Lu YR, Marioni RE, McCoy BM, Mitchell W, Moqri M, Nasirian F, Niimi P, Oh HS, Okundaye B, Parkhitko AA, Peshkin L, Petljak M, Poganik JR, Pridham G, Promislow DEL, Prusisz W, Quiniou M, Raj K, Richard D, Ricon JL, Rutledge J, Scheibye-Knudsen M, Schork NJ, Seluanov A, Shadpour M, Shindyapina AV, Shuken SR, Sivakumar S, Stoeger T, Sugiura A, Sutton NR, Suvorov A, Tarkhov AE, Teeling EC, Trapp A, Tyshkovskiy A, Unfried M, Ward-Caviness CK, Yim SH, Ying K, Yunes J, Zhang B, and Zhavoronkov A
Abstract: To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational issues. What is aging? What causes it? When does it begin? What constitutes rejuvenation? Not only was there no consensus on these and other core questions, but none of the questions received a majority opinion-even regarding the need for consensus itself. Despite many researchers believing they understand aging, their understanding diverges considerably. Importantly, as different processes are labeled as "aging" by researchers, different experimental approaches are prioritized. The survey shed light on the need to better define which aging processes this field should target and what its goals are. It also allowed us to categorize contemporary views on aging and rejuvenation, revealing critical, yet largely unanswered, questions that appear disconnected from the current research focus. Finally, we discuss ways to address the disagreement, which we hope will ultimately aid progress in the field., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)
Published: 2024
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33. The clinical effects of pulsed electromagnetic field therapy for the management of chronic ankle instability: a study protocol for a double-blind randomized controlled trial.

Author: Chia CSM, Fu SC, He X, Cheng YY, Franco-Obregón A, Hua Y, Yung PS, and Ling SK
Subjects: Humans, Double-Blind Method, Prospective Studies, Treatment Outcome, Adult, Exercise Therapy methods, Chronic Disease, Female, Male, Young Adult, Range of Motion, Articular, Middle Aged, Postural Balance, Time Factors, Recovery of Function, Joint Instability therapy, Joint Instability physiopathology, Magnetic Field Therapy methods, Ankle Joint physiopathology, Randomized Controlled Trials as Topic
Abstract: Background: Chronic ankle instability is associated with long-term neuromuscular deficits involving poor postural control and peroneal muscular impairment. Symptoms of chronic ankle instability hinder engagement in physical activity and undermine the patient's quality of life. Despite the existence of various treatment modalities, none has conclusively provided evidence of clinical effectiveness in counteracting neuromuscular deficits, such as arthrogenic muscle inhibition of the peroneal longus (PL). Pulse electromagnetic field therapy employed as an adjunct biophysical therapy can potentially improve stability by mitigating peroneal muscle weakness and by activating the peroneal muscle. We postulate that by combining standard care (muscle strengthening, balance training, and range of motion exercise) with pulse electromagnetic field therapy, postural control stability and peroneal muscle weakness will significantly improve., Methods: This is a prospective, randomized, double-blind, placebo-controlled trial. A total of 48 adults with chronic ankle instability will be recruited and randomly allocated into either the intervention or control groups. The intervention group (n = 24) will receive active pulse electromagnetic field therapy and standard exercise training, while the control group (n = 24) will receive sham pulse electromagnetic field therapy and standard exercise training for 8 weeks. Primary and secondary outcomes will be evaluated at baseline, week 4, 8 as well as at 3-, 6-, and 12-month follow-up visits., Discussion: Chronic ankle instability is a common debilitating condition without a curative conservative treatment. Investigating different treatment modalities will be essential for improving rehabilitation outcomes in this clinical population. This study will investigate the effectiveness of pulsed electromagnetic field therapy on the functional and clinical outcomes in the chronic ankle instability population. This trial may demonstrate this non-invasive biophysical therapy to be an effective measure to help patients with CAI., Trial Registration: ClinicalTrials.gov NCT05500885. Registered on August 13, 2022., Competing Interests: Declarations. Ethics approval and consent to participate {24}: Clinical research ethics approval has been obtained by the Joint CUHK-New Territories East Cluster Clinical Research Ethics Committee (Reference number: 2022.263). In addition, a written informed consent to participate will be obtained from all participants. Consent for publication {32}: Not applicable. This manuscript does not provide personal information, images, or videos relating to the participant. A sample of the consent form will be provided upon reasonable request. Competing interests {28}: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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34. Development and Validation of a Smartphone Application for Neonatal Jaundice Screening.

Author: Ngeow AJH, Moosa AS, Tan MG, Zou L, Goh MMR, Lim GH, Tagamolila V, Ereno I, Durnford JR, Cheung SKH, Hong NWJ, Soh SY, Tay YY, Chang ZY, Ong R, Tsang LPM, Yip BKL, Chia KW, Yap K, Lim MH, Ta AWA, Goh HL, Yeo CL, Chan DKL, and Tan NC
Subjects: Humans, Infant, Newborn, Female, Male, Singapore, Machine Learning, Sensitivity and Specificity, Jaundice, Neonatal diagnosis, Jaundice, Neonatal blood, Smartphone, Neonatal Screening methods, Mobile Applications, Bilirubin blood, Bilirubin analysis
Abstract: Importance: This diagnostic study describes the merger of domain knowledge (Kramer principle of dermal advancement of icterus) with current machine learning (ML) techniques to create a novel tool for screening of neonatal jaundice (NNJ), which affects 60% of term and 80% of preterm infants., Objective: This study aimed to develop and validate a smartphone-based ML app to predict bilirubin (SpB) levels in multiethnic neonates using skin color analysis., Design, Setting, and Participants: This diagnostic study was conducted between June 2022 and June 2024 at a tertiary hospital and 4 primary-care clinics in Singapore with a consecutive sample of neonates born at 35 or more weeks' gestation and within 21 days of birth., Exposure: The smartphone-based ML app captured skin images via the central aperture of a standardized color calibration sticker card from multiple regions of interest arranged in a cephalocaudal fashion, following the Kramer principle of dermal advancement of icterus. The ML model underwent iterative development and k-folds cross-validation, with performance assessed based on root mean squared error, Pearson correlation, and agreement with total serum bilirubin (TSB). The final ML model underwent temporal validation., Main Outcomes and Measures: Linear correlation and statistical agreement between paired SpB and TSB; sensitivity and specificity for detection of TSB equal to or greater than 17mg/dL with SpB equal to or greater than 13 mg/dL were assessed., Results: The smartphone-based ML app was validated on 546 neonates (median [IQR] gestational age, 38.0 [35.0-41.0] weeks; 286 [52.4%] male; 315 [57.7%] Chinese, 35 [6.4%] Indian, 169 [31.0%] Malay, and 27 [4.9%] other ethnicities). Iterative development and cross-validation was performed on 352 neonates. The final ML model (ensembled gradient boosted trees) incorporated yellowness indicators from the forehead, sternum, and abdomen. Temporal validation on 194 neonates yielded a Pearson r of 0.84 (95% CI, 0.79-0.88; P < .001), 82% of data pairs within clinically acceptable limits of 3 mg/dL, sensitivity of 100%, specificity of 70%, positive predictive value of 10%, negative predictive value of 100%, positive likelihood ratio of 3.3, negative likelihood ratio of 0, and area under the receiver operating characteristic curve of 0.89 (95% CI, 0.82-0.96)., Conclusions and Relevance: In this diagnostic study of a new smartphone-based ML app, there was good correlation and statistical agreement with TSB with sensitivity of 100%. The screening tool has the potential to be an NNJ screening tool, with treatment decisions based on TSB (reference standard). Further prospective studies are needed to establish the generalizability and cost-effectiveness of the screening tool in the clinical setting.
Published: 2024
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35. Interactions Between High-Intensity Light and Unrestricted Vision in the Drive for Hyperopia.

Author: Biswas S, Busoy JMF, Barathi VA, Muralidharan AR, Schmetterer L, Kathrani BK, Brennan NA, and Najjar RP
Subjects: Animals, Disease Models, Animal, Choroid pathology, Light adverse effects, Vision, Ocular physiology, Hyperopia physiopathology, Chickens, Refraction, Ocular physiology, Axial Length, Eye pathology
Abstract: Purpose: To evaluate the impact of optical vs. illuminance factors and their duration-dependency on lens-induced hyperopia (LIH) in chick eyes., Methods: Hyperopia was induced in one eye in chicks (10 groups; n = 126) from day 1 after hatching until day 8 using +10-diopter lenses with fellow eyes as controls. One group (LIH) served as the control without any interventions. The remaining groups were exposed to 2, 4, or 6 hours of unrestricted vision (UnV), high-intensity light (HL; 15,000 lux), or both (HL + UnV). Ocular axial length (AL), refractive error, and choroidal thickness were measured on days 1, 4, and 8. Inter-ocular difference (IOD = experimental - contralateral control eye) ± SEM was used to express outcome measures., Results: By day 8, LIH decreased AL (-0.42 ± 0.03 mm) and produced hyperopic refraction (+3.48 ± 0.32 diopters) and choroidal thickening (+85.81 ± 35.23 µm) in the LIH group (all P < 0.001). Exposure to UnV reduced LIH (i.e., hyperopic refraction, axial shortening, and choroidal thickening) in a duration-dependent manner, whereas HL potentiated the development of LIH in a duration-dependent manner. When combined, UnV overpowered HL, with resultant impact on refraction and AL being close to UnV alone, except at 6 hours, when HL + UnV induced shorter AL compared with UnV alone (P = 0.03)., Conclusions: Daily exposure to HL, UnV, and HL + UnV altered LIH in a duration-dependent manner with UnV and LIH producing competing signals. The signal generated by UnV was generally stronger than HL in combined exposure, yet longer durations of HL affected the drive for emmetropization in eyes with UnV.
Published: 2024
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36. T1 Colorectal Cancer: What Are the Barriers to Minimizing Unnecessary Surgical Interventions?

Author: Ichimasa K, Kudo SE, and Misawa M
Published: 2024
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37. Cohort profile: AI-driven national Platform for CCTA for clinicaL and industriaL applicatiOns (APOLLO).

Author: Baskaran L, Leng S, Dutta U, Teo L, Yew MS, Sia CH, Chew NW, Huang W, Lee HK, Vaughan R, Ngiam KY, Lu Z, Wang X, Tan EWP, Cheng NZY, Tan SY, Chan MY, and Zhong L
Subjects: Adult, Aged, Female, Humans, Male, Middle Aged, Coronary Angiography methods, Prospective Studies, Retrospective Studies, Risk Assessment methods, Singapore epidemiology, Observational Studies as Topic, Artificial Intelligence, Computed Tomography Angiography, Coronary Artery Disease
Abstract: Purpose: Coronary CT angiography (CCTA) is well established for the diagnostic evaluation and prognostication of coronary artery disease (CAD). The growing burden of CAD in Asia and the emergence of novel CT-based risk markers highlight the need for an automated platform that integrates patient data with CCTA findings to provide tailored, accurate cardiovascular risk assessments. This study aims to develop an artificial intelligence (AI)-driven platform for CAD assessment using CCTA in Singapore's multiethnic population. We will conduct a hybrid retrospective-prospective recruitment of patients who have undergone CCTA as part of the diagnostic workup for CAD, along with prospective follow-up for clinical endpoints. CCTA images will be analysed locally and by a core lab for coronary stenosis grading, Agatston scoring, epicardial adipose tissue evaluation and plaque analysis. The images and analyses will also be uploaded to an AI platform for deidentification, integration and automated reporting, generating precision AI toolkits for each parameter., Participants: CCTA images and baseline characteristics have been collected and verified for 4196 recruited patients, comprising 75% Chinese, 6% Malay, 10% Indian and 9% from other ethnic groups. Among the participants, 41% are female, with a mean age of 55±11 years. Additionally, 41% have hypertension, 51% have dyslipidaemia, 15% have diabetes and 22% have a history of smoking., Findings to Date: The cohort data have been used to develop four AI modules for training, testing and validation. During the development process, data preprocessing standardised the format, resolution and other relevant attributes of the images., Future Plans: We will conduct prospective follow-up on the cohort to track clinical endpoints, including cardiovascular events, hospitalisations and mortality. Additionally, we will monitor the long-term impact of the AI-driven platform on patient outcomes and healthcare delivery., Trial Registration Number: NCT05509010., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2024
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38. Precision disease management: prognostic biomarker for chronic lung damage in long COVID.

Author: Oo A and Chu JJH
Abstract: Early detection of potential severe disease progression facilitates implementation of relevant precise disease management strategies. MMP-7 is a reliable prognostic biomarker for long COVID persistent lung damage that should be considered for clinical use. https://bit.ly/3Ccxozg., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)
Published: 2024
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39. Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.

Author: Balamurli G, Liew AQX, Tee WW, and Pervaiz S
Subjects: Humans, DNA Methylation, Animals, Gene Expression Regulation, Neoplastic, Neoplasms metabolism, Neoplasms genetics, Neoplasms pathology, Epigenesis, Genetic, Oxidation-Reduction, Cellular Senescence genetics, Reactive Oxygen Species metabolism
Abstract: There is accumulating evidence indicating a close crosstalk between key molecular events regulating cell growth and proliferation, which could profoundly impact carcinogenesis and its progression. Here we focus on reviewing observations highlighting the interplay between epigenetic modifications, irreversible cell cycle arrest or senescence, and cellular redox metabolism. Epigenetic alterations, such as DNA methylation and histone modifications, dynamically influence tumour transcriptome, thereby impacting tumour phenotype, survival, growth and spread. Interestingly, the acquisition of senescent phenotype can be triggered by epigenetic changes, acting as a double-edged sword via its ability to suppress tumorigenesis or by facilitating an inflammatory milieu conducive for cancer progression. Concurrently, an aberrant redox metabolism, which is a function of the balance between reactive oxygen species (ROS) generation and intracellular anti-oxidant defences, influences signalling cascades and genomic stability in cancer cells by serving as a critical link between epigenetics and senescence. Recognizing this intricate interconnection offers a nuanced perspective for therapeutic intervention by simultaneously targeting specific epigenetic modifications, modulating senescence dynamics, and restoring redox homeostasis., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)
Published: 2024
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40. Describing and Mapping the Research Trend of Scientific Publications on Arrhythmogenic Right Ventricular Cardiomyopathy Across Four Decades: A Bibliometric Analysis.

Author: Mo L, Sia CH, Lin W, Zheng X, and Peng K
Subjects: Humans, Periodicals as Topic trends, Periodicals as Topic statistics & numerical data, Bibliometrics, Arrhythmogenic Right Ventricular Dysplasia therapy, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Arrhythmogenic Right Ventricular Dysplasia physiopathology, Biomedical Research trends
Abstract: Objectives: To perform a bibliometric analysis of publications of arrhythmogenic right ventricular cardiomyopathy (ARVC) from 1981 to 2023 to summarize the current publications and explore frontiers on this topic., Methods: We integrated the scientific publications on ARVC in the Web of Science (WOS) Core Collection database from January 1981 to September 2023, using the retrieval strategy of medical subject headings combined with keywords. We focused on articles and reviews that were published in English. Relevant information such as the journal and publisher, the title, authors, organizations, abstract, keywords, published date, and number of citations, were collected. Bibliometric analysis was performed and visualized by the R software and Microsoft Excel., Results: The results revealed a total of 4792 records related to ARVC from the WOS database, and 2992 original articles or reviews which were selected for bibliometric analysis. There were 79 countries and regions, 3724 research institutions, and 12 157 scholars who have published in this topic. The number of scientific publications of ARVC increased year-by-year, with an annual growth rate of 12.12%. We also investigated the top 10 contributing countries, organizations with affiliations, most influential researchers, highest-cited articles, and highest-frequency keywords. In addition, the most active areas of research on ARVC included that of fatal complications, molecular pathological mechanisms, diagnosis, therapy, and prognosis respectively according to the keywords trend analysis., Conclusions: Our study reports the publication landscape of ARVC during the past four decades based on bibliometric analysis. This study provides a deeper understanding of the published literature on ARVC., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)
Published: 2024
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41. Accuracy and reliability of large language models in assessing learning outcomes achievement across cognitive domains.

Author: Teckwani SH, Wong AH, Luke NV, and Low ICC
Subjects: Humans, Reproducibility of Results, Learning physiology, Educational Measurement methods, Artificial Intelligence, Language, Physiology education, Cognition physiology
Abstract: The advent of artificial intelligence (AI), particularly large language models (LLMs) like ChatGPT and Gemini, has significantly impacted the educational landscape, offering unique opportunities for learning and assessment. In the realm of written assessment grading, traditionally viewed as a laborious and subjective process, this study sought to evaluate the accuracy and reliability of these LLMs in evaluating the achievement of learning outcomes across different cognitive domains in a scientific inquiry course on sports physiology. Human graders and three LLMs, GPT-3.5, GPT-4o, and Gemini, were tasked with scoring submitted student assignments according to a set of rubrics aligned with various cognitive domains, namely "Understand," "Analyze," and "Evaluate" from the revised Bloom's taxonomy and "Scientific Inquiry Competency." Our findings revealed that while LLMs demonstrated some level of competency, they do not yet meet the assessment standards of human graders. Specifically, interrater reliability (percentage agreement and correlation analysis) between human graders was superior as compared to between two grading rounds for each LLM, respectively. Furthermore, concordance and correlation between human and LLM graders were mostly moderate to poor in terms of overall scores and across the pre-specified cognitive domains. The results suggest a future where AI could complement human expertise in educational assessment but underscore the importance of adaptive learning by educators and continuous improvement in current AI technologies to fully realize this potential. NEW & NOTEWORTHY The advent of large language models (LLMs) such as ChatGPT and Gemini has offered new learning and assessment opportunities to integrate artificial intelligence (AI) with education. This study evaluated the accuracy of LLMs in assessing an assignment from a course on sports physiology. Concordance and correlation between human graders and LLMs were mostly moderate to poor. The findings suggest AI's potential to complement human expertise in educational assessment alongside the need for adaptive learning by educators.
Published: 2024
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42. Asia-Pacific Real-World Evolocumab Use, LDL-C Reduction, Physician Goals, and Patient Perceptions: HALES Observational Study.

Author: Tse HF, Chang HY, Colquhoun D, Kim JS, Poh KK, Kostner K, Hutayanon P, Cho M, Lange J, Kodiappan K, and Leekha S
Abstract: Introduction: Real-world data are needed to understand the effectiveness of new therapeutic options for low-density lipoprotein cholesterol (LDL-C) reduction in Asia-Pacific clinical practice. Description of evolocumab use among adults with establisHed Atherosclerotic cardiovascuLar diseasE or hypercholesterolemia in ASia-Pacific region (HALES) was performed to better understand characteristics of and clinical decision-making for adults with established atherosclerotic cardiovascular disease/hypercholesterolemia after local evolocumab approval., Methods: The HALES observational study, conducted at 33 sites (Hong Kong, Thailand, South Korea, Singapore, Taiwan, and Australia) comprised (1) chart review of patients who received evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and (2) physician/patient survey and one-time data collection of patients with high cardiovascular risk initiating evolocumab or initiating/continuing non-PCSK9i lipid-lowering therapy. Patients could only enroll in (1) or (2)., Results: Chart review included 724 very high-risk patients initiating evolocumab from regulatory approval to 2021. From median baseline LDL-C of 3.2 mmol/L (123.7 mg/dL), patients had a median percent change in LDL-C of - 60.8% at 1-6 months. Goal achievement increased from 7.9% to 69.8% for < 1.8 mmol/L (< 70 mg/dL) and 4.4% to 57.8% for < 1.4 mmol/L (< 55 mg/dL) from baseline to 12 months. In the one-time data collection, more patients had ≥ 1.8 mmol/L (≥ 70 mg/dL) baseline LDL-C in the evolocumab vs non-PCSK9i group (95.2% and 48.5%, respectively). Surveys found that physicians applied guideline-recommended treatment targets, and patients demonstrated gaps in understanding cardiovascular risk., Conclusion: Real-world, Asia-Pacific data showed that LDL-C reduction after initiating evolocumab was consistent with that observed in other clinical trials and patient populations. Graphical abstract available for this article.·., Competing Interests: Declarations. Conflict of Interest: Hung-Fat Tse reports research funding from Abbott, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Medtronic, Novartis, Pfizer, and Sanofi. Hung-Yu Chang, Kian Keong Poh, Karam Kostner, and Pisit Hutayanon report that they have nothing to declare. David Colquhoun reports research funding from Amgen, Pfizer, AstraZeneca, Novartis, Sanofi, Bayer, and Novo Nordisk. Jung-Sun Kim reports receiving proctoring fees from Abbott Vascular. Meejin Cho, Jeff Lange, Kamlanathan Kodiappan, and Saikiran Leekha are employees and stockholders of Amgen Inc. Ethics Approval: Informed consent was required for patient’s participation in the study. Study protocol and informed consent forms were reviewed and approved by the institutional review board/independent ethics committee (see Supplementary Materials, Supplemental Table S2 for full list by site). Central IRBs were used for sites in Australia and Singapore; local IRBD/ethics committees were used in all other sites. The study was performed in accordance with the Helsinki Declaration of 1964, and its later amendments., (© 2024. The Author(s).)
Published: 2024
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43. Determination of T cell response against XBB variants in adults who received either monovalent wild-type inactivated whole virus or mRNA vaccine or bivalent WT/BA.4-5 COVID-19 mRNA vaccine as the additional booster.

Author: Tang YS, Tan CW, Chong KC, Chen C, Sun Y, Yiu K, Ling KC, Chan KKP, Peiris M, Mok CKP, and Hui DS
Subjects: Humans, Adult, Male, Female, Middle Aged, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Hong Kong, mRNA Vaccines immunology, Vaccines, Synthetic immunology, Vaccines, Synthetic administration & dosage, Young Adult, Aged, Immunization, Secondary, SARS-CoV-2 immunology, SARS-CoV-2 genetics, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, COVID-19 prevention & control, COVID-19 immunology, T-Lymphocytes immunology, Antibodies, Viral blood, Vaccines, Inactivated immunology, Vaccines, Inactivated administration & dosage
Abstract: Objectives: As the SARS-CoV-2 virus evolves more rapidly than vaccines are updated, T cell immunity potentially confers protection against disease progression and death from new variants. In this study, we aimed to assess whether the current boosting vaccination schemes offer sufficient T cell protection against new SARS-CoV-2 variants., Methods: A total of 292 adults who had received the second booster of either monovalent wild-type (WT) vaccines (inactivated virus or mRNA) (Cohort 1) or the second/third booster of bivalent WT/BA.4-5 mRNA vaccine (Cohort 2) were recruited in Hong Kong. All participants showed no serological evidence of recent infection of SARS-CoV-2. Blood samples of each participant were collected before and 1 month after receiving the booster. T cell and antibody responses were determined by flow cytometry and neutralization test, respectively., Results: Among all vaccination strategies, only the adults who had received the bivalent vaccine as the third booster dose significantly elicited T cell responses to the XBB variant. Either monovalent or bivalent mRNA but not inactivated virus vaccine as the second/third booster induced antibody against different XBB variants., Conclusion: Receiving bivalent mRNA vaccine as the third booster is preferable to induce both T cell and antibody responses against XBB., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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44. A synthetic curcumin-like diarylpentanoid analog inhibits rhinovirus infection in H1 hela cells via multiple antiviral mechanisms.

Author: Liew KY, Chee HY, Abas F, Leong SW, Harith HH, Israf DA, Sulaiman MR, and Tham CL
Subjects: Humans, HeLa Cells, Intercellular Adhesion Molecule-1 metabolism, Intercellular Adhesion Molecule-1 genetics, Picornaviridae Infections drug therapy, Virus Replication drug effects, Antiviral Agents pharmacology, Antiviral Agents chemistry, Rhinovirus drug effects, Curcumin pharmacology, Curcumin analogs & derivatives, Curcumin chemistry
Abstract: Background: Rhinovirus (RV) infection is a major cause of common colds and asthma exacerbations, with no antiviral drug available. Curcumin exhibits broad-spectrum antiviral activities, but its therapeutic effect is limited by a poor pharmacokinetics profile. Curcumin-like diarylpentanoid analogs, particularly 2-benzoyl-6-(3,4-dihydroxybenzylidene)cyclohexen-1-ol (BDHBC) and 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), have better solubility and stability compared to curcumin., Objectives: Therefore, this study aims to evaluate and compare the antiviral effects of curcumin, BDHBC, and DHHPD in an in vitro model of RV infection., Methods: The inhibitory effects on RV-16 infection in H1 HeLa cells were assessed using cytopathic effect (CPE) reduction assay, virus yield reduction assay, RT-qPCR, and Western blot. Antiviral effects in different modes of treatment (pre-, co-, and post-treatment) were also compared. Additionally, intercellular adhesion molecule 1 (ICAM-1) expression, RV binding, and infectivity were measured with Western blot, flow cytometry, and virucidal assay, respectively., Results: When used as a post-treatment, BDHBC (EC 50 : 4.19 µM; SI: 8.32) demonstrated stronger antiviral potential on RV-16 compared to DHHPD (EC 50 : 18.24 µM; SI: 1.82) and curcumin (less than 50% inhibition). BDHBC also showed the strongest inhibitory effect on RV-induced CPE, virus yield, vRNA, and viral proteins (P1, VP0, and VP2). Furthermore, BDHBC pre-treatment has a prophylactic effect against RV infection, which was attributed to reduced basal expression of ICAM-1. However, it did not affect virus binding, but exerted virucidal activity on RV-16, contributing to its antiviral effect during co-treatment., Conclusion: BDHBC exhibits multiple antiviral mechanisms against RV infection and thus could be a potential antiviral agent for RV., Competing Interests: Declarations Ethical approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)
Published: 2024
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45. Risk of aspiration pneumonia and hospital mortality in Parkinson disease: A systematic review and meta-analysis.

Author: Chua WY, Wang JDJ, Chan CKM, Chan LL, and Tan EK
Subjects: Humans, Parkinson Disease mortality, Parkinson Disease epidemiology, Pneumonia, Aspiration mortality, Pneumonia, Aspiration epidemiology, Hospital Mortality
Abstract: Background and Purpose: This study was undertaken to conduct a meta-analysis on the prevalence of aspiration pneumonia (AP) and hospital mortality in Parkinson disease (PD) as well as the risk of AP in PD patients compared to controls., Methods: We searched MEDLINE and Embase from inception to 19 March 2024 to identify cross-sectional, cohort, and case-control studies comparing the frequency of AP and hospital mortality in PD patients. We computed risk ratios (RRs) with accompanying 95% confidence intervals (CIs) for each study and pooled the results using a random-effects meta-analysis., Results: A total of 781 studies were initially screened, and 13 studies involving 541,785,587 patients were included. Patients with PD had >3 times higher risk of AP compared to controls (RR = 3.30, 95% CI = 1.82-6.00, p < 0.0001). This increased risk was similar in both cohort studies (RR = 3.01, 95% CI = 1.10-8.24, p = 0.03) and case-control studies (RR = 3.86, 95% CI = 3.84-3.87, p < 0.00001). The prevalence of AP in 12 studies was 2.74% (95% CI = 1.69-4.41), and hospital mortality was 10% in six studies (10.0%, 95% CI = 5.32-18.0). Prevalence of AP was higher in studies with smaller sample size (5.26%, 95% CI = 3.08-8.83 vs. 2.06%, 95% CI = 1.19-3.55, p = 0.02)., Conclusions: Our meta-analysis showed that patients with PD had >3 times higher risk of AP, with an average 2.74% prevalence and 10.0% hospital mortality. Early recognition and treatment of AP in PD patients will help reduce morbidity and mortality. A multidisciplinary holistic approach is needed to address the multifactorial causes of AP., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
Published: 2024
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46. Home-based monitoring of cerebral oxygenation in response to postural changes using near-infrared spectroscopy.

Author: Klop M, Claassen JAHR, Floor-Westerdijk MJ, van Wezel RJA, Maier AB, and Meskers CGM
Subjects: Humans, Female, Male, Aged, Reproducibility of Results, Aged, 80 and over, Posture physiology, Cerebrovascular Circulation physiology, Spectroscopy, Near-Infrared methods, Hypotension, Orthostatic physiopathology, Feasibility Studies
Abstract: Orthostatic hypotension (OH) is prevalent in older adults and can cause falls and hospitalization. Diagnostic intermittent blood pressure (BP) measurements are only a proxy for cerebral perfusion and do not reflect daily-life BP fluctuations. Near-infrared spectroscopy (NIRS)-measured cerebral oxygenation potentially overcomes these drawbacks. This study aimed to determine feasibility, face validity, and reliability of NIRS in the home environment. Ten participants with OH (2 female, mean age 77, SD 3.7) and 11 without OH (5 female, mean age 78, SD 6.7) wore a NIRS sensor at home on two different days for 10-11 h per day. Preceded by a laboratory-situated test, cerebral oxygenation was measured during three standardized supine-stand tests per day and during unsupervised daily life activities. Data availability, quality, and user experience were assessed (feasibility), as well as differences in posture-related oxygenation responses between participants with and without OH and between symptomatic (dizziness, light-headedness, blurred vision) and asymptomatic postural changes (face validity). Reliability was assessed through repetitive supine-stand tests. Up to 80% of the standardized home-based supine-stand tests could be analyzed. Oxygenation recovery values were lower for participants with OH (p = 0 .03-0.15); in those with OH, oxygenation showed a deeper maximum drop for symptomatic than asymptomatic postural changes (p = 0.04). Intra-class correlation coefficients varied from 0.07 to 0.40, with no consistent differences over measurements. This proof-of-concept study shows feasibility and face validity of at-home oxygenation monitoring using NIRS, confirming its potential value for diagnosis and monitoring in OH and OH-related symptoms. Further data are needed for conclusions about reliability., (© 2024. The Author(s).)
Published: 2024
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47. Evaluation of the psychometric performance of the Spanish and Catalan versions of the patient reported experiences and Outcomes of Safety in Primary Care (PREOS-PC)-Compact questionnaire.

Author: Fiol-deRoque MA, Valderas JM, Arias de la Torre J, Serrano-Ripoll MJ, Gens-Barberà M, Sánchez-Freire E, Martín-Luján FM, Olry de Labry A, and Ricci-Cabello I
Subjects: Humans, Cross-Sectional Studies, Psychometrics, Reproducibility of Results, Patient Reported Outcome Measures, Primary Health Care
Abstract: Background: Patients provide a unique, irreplaceable, and essential perspective in evaluating patient safety. The suite of Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) tools are a notable exception to the scarcity of patient-reported patient safety measures. Full evaluation of their performance has only been attempted for the English version, thereby limiting its international applicability., Objectives: To assess the psychometric performance of the Spanish and Catalan versions of the PREOS-PC-Compact., Methods: Cross-sectional validation study. We used Classical Test Theory methods to examine scale score distribution, internal consistency, and construct validity; and Item Response Theory (IRT) methods to further explore construct validity., Results: 3287 patients completed the Spanish version, and 1007 the Catalan version. Similar results were obtained for both versions. Confirmatory Factor Analysis supported a single construct for each scale. The correlations between PREOS-PC-Compact scales and known group analysis suggested adequate construct validity (inconclusive for known groups at the provider level). All four multi-item scales demonstrated adequate internal consistency reliability (α > 0.7), which was only confirmed for test-retest reliability for 'Practice activation.' A sample between 60-90 patients per practice was estimated sufficient to produce scores with reliability > 0.7 for all scales except for harm scales. IRT models showed disordered thresholds for 'Practice activation' and 'Harm burden' but showed excellent fit after reducing the response categories., Conclusion: The Spanish and Catalan versions of the PREOS-PC-Compact are broadly valid and reliable tools to measure patient safety in Spanish primary care centres; confirmation of lower-than-expected test-rest reliability merits further examination .
Published: 2024
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48. Upregulation of hepatic nuclear receptors in extremely preterm ovine fetuses undergoing artificial placenta therapy.

Author: Ikeda H, Watanabe S, Sato S, Fee EL, Carter SWD, Kumagai Y, Takahashi T, Kawamura S, Hanita T, Illanes SE, Choolani MA, Saito M, Kikuchi A, Kemp MW, and Usuda H
Subjects: Infant, Newborn, Pregnancy, Infant, Sheep, Animals, Female, Humans, Up-Regulation, Liver, Fetus, Receptors, Cytoplasmic and Nuclear, RNA, Messenger, Infant, Extremely Premature, Placenta
Abstract: Objective: Extremely preterm infants have low Nuclear Receptor (NR) expression in their developing hepatobiliary systems, as they rely on the placenta and maternal liver for compensation. NRs play a crucial role in detoxification and the elimination of both endogenous and xenobiotic substances by regulating key genes encoding specific proteins. In this study, we utilized an Artificial Placenta Therapy (APT) platform to examine the liver tissue expression of NRs of extremely preterm ovine fetuses. This fetal model, resembling a "knockout placenta," lacks placental and maternal support, while maintaining a healthy extrauterine survival., Methods: Six ovine fetuses at 95 ± 1 d gestational age (GA; term = ∼150 d)/∼600 g delivery weight were maintained on an APT platform for a period of 120 h (APT Group). Six age-matched, in utero control fetuses were delivered at 99-100 d GA (Control Group). Fetal liver tissue samples and blood samples were collected at delivery from both groups and assessed mRNA expression of NRs and target transporters involved in the hepatobiliary transport system using quantitative PCR. Data were tested for group differences with ANOVA ( p < .05 deemed significant)., Results: mRNA expression of NRs was identified in both the placenta and the extremely preterm ovine fetal liver. The expression of HNF4α , LRH1 , LXR , ESR1 , PXR , CAR , and PPARα/γ were significantly elevated in the liver of the APT Group compared to the Control Group. Moreover, target transporters NTCP , OATP1B3 , BSEP , and MRP4 were upregulated, whereas MRP2 and MRP3 were unchanged. Although there was no evidence of liver necrosis or apoptotic changes histologically, there was an impact in the fetal liver of the ATP group at the tissue level with a significant increase in TNFα mRNA, a cytokine involved in liver inflammation, and blood elevation of transaminases., Conclusion: A number of NRs in the fetal liver were significantly upregulated after loss of placental-maternal support. However, the expression of target transporter genes appeared to be insufficient to compensate role of the placenta and maternal liver and avoid fetal liver damage, potentially due to insufficient excretion of organic anions.
Published: 2024
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49. Acute NETosis from organophosphate poisoning.

Author: Fan BE, Teo GFA, Lim KGE, Wong SW, Lai YW, Kuperan P, and Wong SL
Published: 2024
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50. Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

Author: Salim H, Musmar B, Adeeb N, Yedavalli V, Lakhani D, Grewal SS, El Naamani K, Henninger N, Sundararajan SH, Kühn AL, Khalife J, Ghozy S, Scarcia L, Tan BY, Regenhardt RW, Heit JJ, Cancelliere NM, Bernstock JD, Rouchaud A, Fiehler J, Sheth S, Puri AS, Dyzmann C, Colasurdo M, Barreau X, Renieri L, Filipe JP, Harker P, Radu RA, Abdalkader M, Klein P, Marotta TR, Spears J, Ota T, Mowla A, Jabbour P, Biswas A, Clarençon F, Siegler JE, Nguyen TN, Varela R, Baker A, Essibayi MA, Altschul D, Gonzalez NR, Möhlenbruch MA, Costalat V, Gory B, Stracke CP, Aziz-Sultan MA, Hecker C, Shaikh H, Liebeskind DS, Pedicelli A, Alexandre AM, Tancredi I, Faizy TD, Kalsoum E, Lubicz B, Patel AB, Pereira VM, Guenego A, and Dmytriw AA
Subjects: Humans, Aged, Male, Female, Retrospective Studies, Aged, 80 and over, Treatment Outcome, Middle Aged, Stroke mortality, Anticoagulants therapeutic use, Anticoagulants adverse effects, Anticoagulants administration & dosage, Ischemic Stroke therapy, Ischemic Stroke mortality, Thrombectomy methods, Thrombectomy adverse effects
Abstract: Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood., Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications., Results: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups., Conclusion: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.
Published: 2024
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