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

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18,200 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. Venom Peptide Repertoire of the European Myrmicine Ant Manica rubida: Identification of Insecticidal Toxins

Author: Samira R. Aili, Elsa Bonnafé, Benjamin Lefranc, Graham M. Nicholson, Axel Touchard, Valentine Barassé, Mrinalini, Laurent Coquet, Alain Dejean, R. Manjunatha Kini, Thierry Jouenne, Pierre Escoubas, Michel Treilhou, Christophe Klopp, Nathan Téné, Jérôme Leprince, Biochimie et Toxicologie des Substances Bioactives (BTSB), Institut national universitaire Champollion [Albi] (INUC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, School of Environmental and Life Sciences - SELS (Callaghan, Australia), University of Newcastle [Australia] (UoN), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecologie des forêts de Guyane (UMR ECOFOG), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Protein Science laboratory, Department of biological Sciences, Faculty of Science, National University of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Polymères Biopolymères Surfaces (PBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Venometech, European Commission, Region Normandie through the European Regional Development Fund (ERDF), and Southeast Asian Biodiversity Genomics Center, National University of Singapore - R-154-000-648-646
Subjects: 0301 basic medicine, pyroglutamate, Peptide, Lucilia caesar, Venom, glycosylated toxin, Manica rubida, medicine.disease_cause, Biochemistry, Ant venom, 03 medical and health sciences, peptidome, medicine, Threonine, polycationic α-helix, chemistry.chemical_classification, reversible neurotoxicity, 030102 biochemistry & molecular biology, biology, Toxin, [SDV.BA]Life Sciences [q-bio]/Animal biology, General Chemistry, biology.organism_classification, medicine.disease, ANT, 030104 developmental biology, chemistry, predation, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract: International audience; Using an integrated transcriptomic and proteomic approach, we characterized the venom peptidome of the European red ant, Manica rubida. We identified 13 "myrmicitoxins" that share sequence similarities with previously identified ant venom peptides, one of them being identified as an EGF-like toxin likely resulting from a threonine residue modified by O-fucosylation. Furthermore, we conducted insecticidal assays of reversed-phase HPLC venom fractions on the blowfly Lucilia caesar, permitting us to identify six myrmicitoxins (i.e., U3-, U10-, U13-, U20-MYRTX-Mri1a, U10-MYRTX-Mri1b, and U10-MYRTX-Mri1c) with an insecticidal activity. Chemically synthesized U10-MYRTX-Mri1a, -Mri1b, -Mri1c, and U20-MYRTX-Mri1a irreversibly paralyzed blowflies at the highest doses tested (30-125 nmol·g-1). U13-MYRTX-Mri1a, the most potent neurotoxic peptide at 1 h, had reversible effects after 24 h (150 nmol·g-1). Finally, U3-MYRTX-Mri1a has no insecticidal activity, even at up to 55 nmol·g-1. Thus, M. rubida employs a paralytic venom rich in linear insecticidal peptides, which likely act by disrupting cell membranes.
Published: 2020
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11. 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

12. 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

13. 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

14. 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

15. 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

16. 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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17. 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

18. 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

19. 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

20. 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

21. Estimating prevalence of subjective cognitive decline acrossinternational cohort studies of ageing: a cosmic study

Author: Roehr, Susanne, pabst, Alexander, Riedel-Heller, Steffi G., Ancelin, Marie-Laure, Anstey, Kaarin J., Brayne, Carol, Brodaty, Henry, Ganguli, Mary, Guerchet, Maëlenn, Katz, Mindy, Kim, Ki Woong, Koehler, Sebastian, Kumagai, Shuzo, Lipton, Richard, Lobo, Antonio, Ng, Tze Pin, Guaita, Antonio, Preux, Pierre-Marie, Ritchie, Karen, Shahar, Suzana, Turana, Yuda, van Boxtel, Martin, Lipnicki, Darren, Sachdev, Perminder, Institute of Social Medicine, Occupational Health and Public Health, Universität Leipzig [Leipzig], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), Centre for Healthy Brain Ageing [Sydney], The University of Sydney, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert Einstein College of Medicine [New York], Seoul National University Bundang Hospital, Department of Psychiatry and Neuropsychology [Maastricht], Maastricht University [Maastricht], Kyushu University [Fukuoka], Department of Medicine [Zaragoza, Spain], University of Zaragoza - Universidad de Zaragoza [Zaragoza], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Yong Loo Lin School of Medicine, National University of Singapore, Seoul National University [Seoul] (SNU), Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, University Malaysia, Atma Jaya Yogyakarta University, Dementia Collaborative Research Centre, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: hemic and lymphatic diseases, preclinical Alzheimer's disease, harmonization, COSMIC, prevalence, item response theory, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, individual participant data, subjective cognitive decline, cross-cohort analysis
Abstract: International audience; Abstract:INTRODUCTION Subjective cognitive decline (SCD), i.e. a self-experienced decline in cognitive ability in the absence of objective cognitive impairment, is recognized as the first notable cognitive syndrome in the preclinical stage of Alzheimer’s disease (AD) and other dementias. However, estimates on the prevalence of SCD are scarce. Therefore, we aimed to estimate SCD prevalence based on consensus research criteria for SCD across international cohort studies of ageing.METHODS Analyses were based on the combined baseline data for 16 international cohort studies from 15 countries. All studies were members of COSMIC (Cohort Studies of Memory in an International Consortium). Qualitative/semantic and quantitative (Item Response Theory/IRT) approaches were used to a) harmonize SCD items across studies and b) derive SCD prevalence estimates, applying a uniform operationalization algorithm based on current SCD research criteria and implementation guidelines.RESULTS Analyses included data from 39,387 cognitively unimpaired individuals at least 60 years of age (mean age: M = 73.1 years; SD = 7.1 years); 57.7% were women. Variety of SCD items was high between studies; however, qualitative harmonization (QH) and IRT both robustly suggested a total SCD prevalence of around one quarter (QH: 23.8%, 95%CI = 23.3%-24.4%; IRT: 25.6%, 95%CI = 25.1%-26.1%) across uniform criteria. SCD prevalence was lower in a) women compared to men, b) individuals with educational levels above primary, c) high-income countries compared to countries with lower income levels, and d) in White people compared to Asian people.DISCUSSION SCD occurs relatively frequently in ageing populations around the globe, as estimated across 16 international cohorts. However, SCD measurement techniques vary in the absence of standardized instruments, and therefore, our prevalence estimates may be associated with someinaccuracy. Nevertheless, with almost a quarter of all elderly reporting SCD, further investigation of its significance as the first cognitive syndrome in preclinical AD and other dementia is needed. This may lead to improved strategies for early identification and prevention of dementia.
Published: 2020

22. 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

23. The longitudinal relationship between early-life screen viewing and 24-hour movement behaviours -findings from a multi-ethnic birth cohort study

Author: Chen, Bozhi, Bernard, Jonathan, Padmapriya, Natarajan, Ning, Yilin, Cai, Shirong, Lança, Carla, Tan, Kok Hian, Yap, Fabian, Chong, Yap-Seng, Shek, Lynette, Godfrey, Keith, Saw, Seang, Chan, Shiao-Yng, Eriksson, Johan, Tan, Chuen, Müller-Riemenschneider, Falk, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Yong Loo Lin School of Medicine, National University of Singapore, NUS Graduate School of Integrative Sciences and Engineering [Singapore, Singapore], Singapore Eye Research Institute [Singapore] (SERI), KK Women’s and Children’s Hospital (KKH), Duke-NUS Graduate Medical School, Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], National University Health System, Medical Research Council, University of Southampton, Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Helsinki, Berlin Institute of Health (BIH), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Duke-NUS Medical School [Singapore], Nanyang Technological University (NTU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Bernard, Jonathan
Subjects: [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020
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24. 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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25. Critical role of free cytosolic calcium, but not uncoupling, in mitochondrial permeability transition and cell death induced by diclofenac oxidative metabolites in immortalized human hepatocytes

Author: Boelsterli, Urs [Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 (Singapore) and Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117597 (Singapore)]
Published: 2006
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26. Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

Author: Boelsterli, Urs [Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 (Singapore) and Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117597 (Singapore)]
Published: 2006
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27. Action of diclofenac on kidney mitochondria and cells

Author: Wong, Kim [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore 119260 (Singapore)]
Published: 2006
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28. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide

Author: Moore, Philip [Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 (Singapore)]
Published: 2006
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29. The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

Author: Tang, Bor [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597 (Singapore)]
Published: 2006
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30. 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

31. 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, E.H. and Bennoor, K.S. and Benson, M. and Bertorello, L. and Białoszewski, A.Z. and Bieber, T. and Bialek, S. and Bjermer, L. and Blain, H. and Blasi, F. and Blua, A. and Bochenska Marciniak, M. and Bogus-Buczynska, I. and Boner, A.L. and Bonini, M. and Bonini, S. and Bosnic-Anticevich, C.S. and Bouchard, J. and Boulet, L.P. and Bourret, R. and Bousquet, P.J. and Braido, F. and Briedis, V. and Brightling, C.E. and Brozek, J. and Bucca, C. and Buhl, R. and Buonaiuto, R. and Panaitescu, C. and Burguete Cabañas, M.T. and Burte, E. and Bush, A. and Caballero-Fonseca, F. and Caillot, D. and Caimmi, D. and Calderon, M.A. and Camargos, P.A.M. and Camuzat, T. and Canfora, G. and Canonica, G.W. and Carlsen, K.H. and Carreiro-Martins, P. and Carriazo, A.M. and Carr, W. and Cartier, C. and Castellano, G. and Cepeda, A.M. and Chen, Y. and Chiron, R. and Chivato, T. and Chkhartishvili, E. and Chuchalin, A.G. and Chung, K.F. and Ciaravolo, M.M. and Ciceran, A. and Cingi, C. and Ciprandi, G. and Carvalho Coehlo, A.C. and Colas, L. and Colgan, E. and Coll, J. and Conforti, D. and Correia de Sousa, J. and Cortés-Grimaldo, R.M. and Corti, F. and Costa-Dominguez, M.C. and Courbis, A.L. and Cox, L. and Crescenzo, M. and Custovic, A. and Czarlewski, W. and Dahlen, S.E. and Dario, C. and da Silva, J. and Dauvilliers, Y. and Darsow, U. and De Blay, F. and De Carlo, G. and de Fátima Emerson, M. and De Martino, B. and de Paula Motta Rubini, N. and Deleanu, D. and Denburg, J.A. and Di Capua Ercolano, S. and Di Carluccio, N. and Didier, A. and Dokic, D. and Dominguez-Silva, M.G. and Douagui, H. and Dray, G. and Dubakiene, R. and Durham, S.R. and Du Toit, G. and Dykewicz, M.S. and El-Gamal, Y. and Eklund, P. and Farrell, J. and Farsi, A. and Ferreira de Mello, J., Jr. and Ferrero, J. and Fink-Wagner, A. and Fiocchi, A. and Fonseca, J.A. and Forti, S. and Fuentes-Perez, J.M. and Gálvez-Romero, J.L. and Gamkrelidze, A. and Garcia-Aymerich, J. and García-Cobas, C.Y. and Garcia-Cruz, M.H. and Genova, S. and George, C. and Gereda, J.E. and Gerth van Wijk, R. and Gomez, R.M. and Gómez-Vera, J. and González Diaz, S. and Gotua, M. and Grisle, I. and Guidacci, M. and Guldemond, N.A. and Gutter, Z. and Guzmán, M.A. and Hajjam, J. and Hernández, L. and Hourihane, J.O.’.B. and Huerta-Villalobos, Y.R. and Humbert, M. and Iaccarino, G. and Jares, E.J. and Jassem, E. and Johnston, S.L. and Joos, G. and Jung, K.S. and Jutel, M. and Kaidashev, I. and Kalayci, O. and Kalyoncu, A.F. and Karjalainen, J. and Kardas, P. and Keil, T. and Keith, P.K. and Khaitov, M. and Khaltaev, N. and Kleine-Tebbe, J. and Kowalski, M.L. and Kuitunen, M. and Kuna, P. and Kupczyk, M. and Krzych-Fałta, E. and Lacwik, P. and Lauri, D. and Lavrut, J. and Le, L.T.T. and Lessa, M. and Levato, G. and Li, J. and Lieberman, P. and Lipiec, A. and Lipworth, B. and Lodrup Carlsen, K.C. and Louis, R. and Luna-Pech, J.A. and Maciej, K. and Magnan, A. and Mahboub, B. and Maier, D. and Mair, A. and Majer, I. and Malva, J. and Mandajieva, E. and Manning, P. and De Manuel Keenoy, E. and Marshall, G.D. and Masjedi, M.R. and Maspero, J.F. and Matta Campos, J.J. and Matos, A.L. and Maurer, M. and Mavale-Manuel, S. and Mayora, O. and Medina-Avalos, M.A. 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 Momas, I. and Montefort, S. and Mora Bogado, D. and Morato-Castro, F.F. and Mota-Pinto, A. and Moura Santo, P. and Münter, L. and Muraro, A. and Naclerio, R. and Nadif, R. and Nalin, M. and Namazova-Baranova, L. and Niedeberger, V. and Nekam, K. and Neou, A. and Nieto, A. and Nogueira-Silva, L. and Nogues, M. and Novellino, E. and Nyembue, T.D. and O’hehir, R.E. and Odzhakova, C. and Ohta, K. and Okubo, K. and Ortega Cisneros, M. and Ouedraogo, S. and Pali-Schöll, I. and Panzner, P. and Papadopoulos, N.G. and Park, H.S. and Papi, A. and Passalacqua, G. and Paulino, E. and Pawankar, R. and Pedersen, S. and Pereira, A.M. and Persico, M. and Phillips, J. and Pigearias, B. and Pin, I. and Pitsios, C. and Plavec, D. and Pohl, W. and Popov, T.A. and Potter, P. and Pozzi, A.C. and Price, D. and Puy, R. and Pugin, B. and Pulido Ross, R.E. and Przemecka, M. and Rabe, K.F. and Raciborski, F. and Rajabian-Soderlund, R. and Ribeirinho, I. and Rimmer, J. and Rizzo, J.A. and Rizzo, M.C. and Robalo-Cordeiro, C. and Rodenas, F. and Rodo, X. and Rodriguez Gonzalez, M. and Rodriguez-Mañas, L. and Rolland, C. and Rodrigues Valle, S. and Roman Rodriguez, M. and Romano, A. and Rolla, G. and Romano, M. and Rosado-Pinto, J. and Rosario, N. and Rottem, M. and Sagara, H. and Sanchez-Borges, M. and Sastre-Dominguez, J. and Scadding, G.K. and Schunemann, H.J. and Scichilone, N. and Schmid-Grendelmeier, P. and Shamai, S. and Sierra, M. and Simons, F.E.R. and Siroux, V. and Sisul, J.C. and Skrindo, I. and Solé, D. and Somekh, D. and Sondermann, M. and Sooronbaev, T. and Sorensen, M. and Sorlini, M. and Spranger, O. and Stellato, C. and Stelmach, R. and Stukas, R. and Sunyer, J. and Strozek, J. and Szylling, A. and Tebyriçá, J.N. and Thibaudon, M. and To, T. and Tomazic, P.V. and Trama, U. and Triggiani, M. and Suppli Ulrik, C. and Urrutia-Pereira, M. and Valenta, R. and Valero, A. and van Ganse, E. and van Hague, M. and Vandenplas, O. and Vezzani, G. and Vasankari, T. and Vatrella, A. and Verissimo, M.T. and Viart, F. and Viegi, G. and Vicheva, D. and Vontetsianos, T. and Wagenmann, M. and Walker, S. and Wallace, D. and Wang, D.Y. and Werfel, T. and Westman, M. and Williams, D.M. and Williams, S. and Wilson, N. and Wright, J. and Wroczynski, P. and Yakovliev, P. and Yawn, B.P. and Yiallouros, P.K. and Yusuf, O.M. and Zar, H.J. and Zhang, L. and Zhong, N. and Zernotti, M.E. and Zidarn, M. and Zubrinich, C. and Zurkuhlen, A., MACVIA-France, Fondation Partenariale FMC VIA-LR, CHRU Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, Montpellier, 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, 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

32. 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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33. 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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34. 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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35. Characterization of two cysteine proteases secreted by Blastocystis ST7, a human intestinal parasite

Author: Ivan Wawrzyniak, Frédéric Delbac, Eric Viscogliosi, Kevin S. W. Tan, Hicham El Alaoui, Catherine Texier, Philippe Poirier, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratory of Molecular and Cellular Parasitology - Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and National University of Singapore (NUS)
Subjects: Proteomics, Proteases, Virulence Factors, medicine.medical_treatment, 030231 tropical medicine, Molecular Sequence Data, Intestinal parasite, Virulence, Legumain, medicine.disease_cause, Cathepsin B, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Cysteine Proteases, Tandem Mass Spectrometry, medicine, Humans, Protease Inhibitors, Amino Acid Sequence, 030304 developmental biology, Cathepsin, 0303 health sciences, Blastocystis, Protease, biology, DNA, Protozoan, biology.organism_classification, 3. Good health, Intestines, Cysteine Endopeptidases, Infectious Diseases, Biochemistry, biology.protein, Parasitology, Electrophoresis, Polyacrylamide Gel, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: International audience; Blastocystis spp. are unicellular anaerobic intestinal parasites of both humans and animals and the most prevalent ones found in human stool samples. Their association with various gastrointestinal disorders raises the questions of its pathogenicity and of the molecular mechanisms involved. Since secreted proteases are well-known to be implicated in intestinal parasite virulence, we intended to determine whether Blastocystis spp. possess such pathogenic factors. In silico analysis of the Blastocystis subtype 7 (ST7) genome sequence highlighted 22 genes coding proteases which were predicted to be secreted. We characterized the proteolytic activities in the secretory products of Blastocystis ST7 using specific protease inhibitors. Two cysteine proteases, a cathepsin B and a legumain, were identified in the parasite culture supernatant by gelatin zymographic SDS-PAGE gel and MS/MS analysis. These proteases might act on intestinal cells and disturb gut function. This work provides serious molecular candidates to link Blastocystis spp. and intestinal disorders.
Published: 2012
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36. Complete circular DNA in the mitochondria-like organelles of Blastocystis hominis

Author: Catherine Texier, Patrick Wincker, Christian P. Vivarès, Kevin S. W. Tan, Frédéric Delbac, Marie Diogon, Michaël Roussel, Ivan Wawrzyniak, Arnaud Couloux, Hicham El Alaoui, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-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), Laboratory of Molecular and Cellular Parasitology - Department of Microbiology, National University of Singapore (NUS), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), 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)-Université Paris-Saclay, Yong Loo Lin School of Medicine, National University of Singapore, and Institut de Biologie François JACOB (JACOB)
Subjects: Iron-Sulfur Proteins, MESH: Sequence Analysis, DNA, MESH: Mitochondria, Protein subunit, Iron, Oxidative phosphorylation, Mitochondrion, Biology, DNA sequencing, 03 medical and health sciences, MESH: Blastocystis hominis, Bacterial Proteins, Hydrogenase, Oxidoreductase, Organelle, Animals, Humans, Lobosea, Blastocystis hominis, MESH: Animals, Protozoa, MESH: Bacterial Proteins, Ferredoxin, 030304 developmental biology, Organelles, chemistry.chemical_classification, 0303 health sciences, Blastocystis, MESH: Humans, 030306 microbiology, Sequence Analysis, DNA, Molecules, MESH: Iron-Sulfur Proteins, biology.organism_classification, Mitochondria, Circular DNA, Parasite, Infectious Diseases, Complete, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Biochemistry, MESH: Hydrogenase, MESH: DNA, Circular, Parasitology, DNA, Circular, MESH: Organelles
Abstract: International audience; Blastocystis hominis is an anaerobic parasite of the human intestinal tract belonging to the Stramenopile group. Using genome sequencing project data, we describe here the complete sequence of a 29,270-bp circular DNA molecule that presents mitochondrial features (such as oxidative phosphorylation complex I subunits) but lacks complexes III, IV and V. Transmission electron microscopy analyses reveal that this molecule, as well as mitochondrial (NADH:ubiquinone oxidoreductase subunit 7 (NAD7), beta-succinyl-CoA synthetase (beta-SCS)) and hydrogenosomal (pyruvate ferredoxin oxido-reductase (PFOR), iron-hydrogenase) proteins, are located within double-membrane surrounded-compartments known as mitochondria-like organelles (MLOs). As there is no evidence for hydrogen production by this organism, we suggest that MLOs are more likely anaerobic mitochondria.
Published: 2008
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37. 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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38. Teaching NeuroImage: Prognostication of X-Linked Adrenoleukodystrophy Based on the Loes Neuroimaging Score.

Author: Lim CYS, Ng NBH, Han V, Yong C, Loke KY, and Lin JB
Published: 2024
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39. Impact of depressive symptoms on motivation in persons with post-COVID-19 condition.

Author: West J, Kwan ATH, Teopiz KM, Guo Z, Le GH, Badulescu S, Rhee TG, Wong S, Cao B, Ho R, Rosenblat JD, Mansur RB, Phan L, Subramaniapillai M, and McIntyre RS
Abstract: Objective: The World Health Organization (WHO) has defined Post-COVID-19 Condition (PCC) as the onset of symptoms within three months after resolution of an acute SARS-CoV-2 infection, wherein symptoms persist for at least two months and cannot be explained by another medical/psychiatric condition. Persons living with PCC report debilitating symptoms including, but not limited to, depressive symptoms and motivational deficits. The aim of this post-hoc analysis was to evaluate the association between depressive symptoms and motivation in adults with PCC., Methods: We conducted a post-hoc analysis of an 8-week, double-blind, randomized, placebo-controlled trial evaluating adults (18 years or older) in Canada with WHO-defined PCC and cognitive symptoms. This post-hoc analysis is comprised of baseline data that evaluates the association between depressive symptom severity measured by the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16) and motivational systems measured by the Behavioral Inhibition System/Behavioral Activation System Questionnaire (BIS/BAS)., Results: There was a statistically significant association between depressive symptoms and BIS ( β = -0.041 95% CI [-0.066, -0.016], p<0.05), BAS reward responsiveness ( β = 0.043 95% CI [0.012, 0.074], p<0.05), sex ( β = -0.137 95% CI [-0.266, -0.008], p<0.05), and confirmed COVID-19 infection ( β = 0.196 95% CI [0.061, 0.332], p<0.05)., Conclusions: Depressive symptoms were associated with motivational deficits in persons living with PCC. Optimizing treatment for depressive symptoms may potentially improve aspects of motivational impairment amongst persons with PCC. All patients presenting with MDD and a history of COVID-19 infection should be assessed for the presence of PCC.
Published: 2024
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40. Increased expression of epithelial-mesenchymal transition markers associated with recurrence of sinonasal inverted papilloma.

Author: Tu J, Jiang F, Liu J, Ong HH, Huang Z, Wang K, Luo Q, Shi L, Ye J, and Wang D
Abstract: Key Points: Sinonasal inverted papilloma (SNIP) is a benign epithelial proliferative disease with a high recurrence rate. The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of SNIP remains unclear. EMT marker expression is elevated in SNIP tissues and is associated with its recurrence., (© 2024 ARS‐AAOA, LLC.)
Published: 2024
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41. Cardiogenic shock in the setting of acute myocardial infarction: Still a difficult entity to treat.

Author: Sia CH and Ho AFW
Published: 2024
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42. A Review of Contact Lens Regulations in the Asia Pacific Region.

Author: Lee JRJ, Yee TH, Levitz D, Lim BXH, Mehta JS, Stapleton F, and Lim CHL
Abstract: Abstract: The increased usage of nonrefractive cosmetic contact lenses in Asia and a trend toward increased online purchasing of both refractive and cosmetic contact lenses poses unique challenges in the management of contact lens-related complications. However, regulations have lagged behind this increased uptake in the community. This paper reviews regulations surrounding the manufacturing, import, and distribution of contact lenses in the Asia Pacific region and compares them with international regulations from the European Union and United States. It found a need for more specific regulations and closer surveillance targeted at new trends in contact lens purchasing and usage. This paper also found a need for more effective enforcement of current regulations., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)
Published: 2024
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43. The number needed to teach: A framework for health professions education.

Author: Low MJW, Miller DT, and Zuckerman MD
Abstract: What Is the Educational Challenge?: Health professions education is continually limited by financial resources with increasing demands for accountability. Judicious resource allocation across competing demands rests on frameworks for analyzing and comparing costs and outcomes., What Are the Proposed Solutions?: We suggest health professions educators use the number needed to teach (NNTe) for reporting and communicating such analyses for teaching and learning., What Are the Potential Benefits to a Wider Global Audience?: The NNTe has the potential to improve reporting and understanding of effectiveness of teaching and learning, similar to how the number needed to treat (NNTr) has improved communication of the effectiveness of clinical interventions. Prior widespread understanding of NNTr will likely allow NNTe to be easily grasped by most clinical educators and those responsible for resource allocation decisions. This article describes the origins of and parallels between NNTr and NNTe, which summarizes and presents in concrete terms to educators, learners, and institutional leadership the investment required to prevent or produce a specific outcome. The calculation and interpretation of NNTe is demonstrated using examples from published real-world data, and its potential benefits, limitations and applications are explored., What Are the Next Steps?: Next steps include explorations of the variety of contexts and comparisons that can be interpreted using NNTe and its corollary, the Number Need to Harm, and how recipients interpret and act upon NNTe.
Published: 2024
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44. Proxy medical decision-making: national survey.

Author: Phua AI, Zakaria C, Pakianathan PV, Chan N, Lim MJR, Liew TM, Koh GCH, and Foong PS
Abstract: Objectives: Population ageing and increased care needs lead to adults making consequential medical decisions for others, potentially impacting treatment and end of life. We aim to describe the prevalence of medical decision-making by proxy among the national population and associated demographic and care factors., Methods: We designed a cross-sectional online survey with a nationally representative adult cohort with an 80% participation rate. 311 Singapore residents completed the survey., Results: 73% of respondents reported having ever assisted others with medical decisions, while 58% have ever assisted with activities of daily living (ADLs), and 88% with instrumental ADLs (IADLs). Having a digital caregiver account, having a lasting power of attorney as a donee and assisting with ADLs and IADLs are significantly associated with proxy medical decision-making. Gender, ethnicity, income and age did not appear to have a significant impact., Conclusions: A majority of Singapore adults assist others with caregiving tasks and medical decision-making, often informally, which may increase decisional burden for caregivers and potential abuse of power. There may be value in increasing the uptake of digital caregiver accounts and advance care arrangements to increase formalised proxy medical decision-making., 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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45. Subregion-specific thalamocortical functional connectivity, executive function, and social behavior in children with autism spectrum disorders.

Author: Chuah JSM, Manahan AMA, Chan SY, Ngoh ZM, Huang P, and Tan AP
Abstract: The thalamus has extensive cortical connections and is an integrative hub for cognitive functions governing social behavior. This study examined (1) associations between thalamocortical resting-state functional connectivity (RSFC) and social behavior in children and (2) how various executive function (EF) subdomains mediate the association between thalamocortical RSFC and social behavior. Children from the autism brain imaging data exchange (ABIDE) initiative with neuroimaging, behavioral, and demographic data were included in our study (age < 14, ASD; n = 207, typically developing; n = 259). Thalamocortical RSFC was examined for associations with social communication and interaction (SCI) scores (SRS; social responsiveness scale) using Spearman's rank-order correlation, first in ASD children and then in typically developing children. This was followed by a more granular analysis at the thalamic subregion level. We then examined the mediating roles of eight EF subdomains in ASD children (n = 139). Right thalamus-default mode network (DMN) RSFC was significantly associated with SCI scores in ASD children (ρ = 0.23, p FDR = 0.012), primarily driven by the medial (ρ = 0.22, p FDR = 0.013), ventral (ρ = 0.17, p FDR = 0.036), and intralaminar (ρ = 0.17, p FDR = 0.036) thalamic subregions. Cognitive flexibility (ACME = 0.13, p unc = 0.016) and emotional control (ACME = 0.08, p unc = 0.020) significantly mediated the association between right thalamus-DMN RSFC and SCI scores. This study provided novel insights into the association between thalamocortical RSFC and social behavior in ASD children at the thalamic subregion level, providing higher levels of precision in brain-behavior mapping. Cognitive flexibility and emotion regulation were highlighted as potential targets to ameliorate the downstream effects of altered thalamocortical connectivity to improve social outcomes in ASD children., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)
Published: 2024
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46. Low-level light therapy and intense pulse light therapy in meibomian gland dysfunction. A systematic review and meta-analysis.

Author: Chan KE, Lau BSR, Lim BXH, Du R, Giannaccare G, Tong L, Stapleton F, and Lim CHL
Abstract: Background: Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease, affecting over a third of the global population. This disease is associated with ocular discomfort, reduced visual quality, and quality of life. Novel treatments like Intense Pulse Light (IPL) therapy and Low-Level Light Therapy (LLLT) have been reported to be useful in refractory MGD treatment. However, no systematic review has explored the utility of combining these two therapies., Methods: Medline, Embase, and CENTRAL databases were searched for articles on LLLT + IPL therapy in MGD. A meta-analysis of single means was conducted to assess clinical endpoints., Results: Analysis of 12 studies showed that LLLT + IPL therapy in MGD patients led to a significant decrease in Ocular Surface Disease Index score (MD: -22.8, 95 %CI: -29.1 to -16.5, I 2 = 97.5 %, p < 0.001), and a significant increase in both Tear Break-up Time (MD: 2.2 s, 95 %CI: 0.9 s to 3.4 s, I 2 = 98.6 %, p < 0.001) and Schirmer test (MD: 1.5 mm, 95 %CI: 0.6 mm to 2.5 mm, I 2 = 0.0 %, p = 0.001) at ≤ 3 months post treatment. These improvements were sustained in a sensitivity analysis at endpoints ≥ 6 months post treatment. While the percentage of loss of meibomian gland area (n = 4, MD: -3.8 %, 95 %CI: -7.2 % to -0.4 %, I 2 = 40.0 %, p = 0.031) was reported to be significantly reduced, this was not found to be sustained at endpoints ≥ 6 months post treatment (n = 2, MD: 5.9 %, 95 %CI: 1.8 % to 10.0 %, I 2 = 0.0 %, p = 0.005) in two studies., Conclusions: This meta-analysis provides quantitative evidence supporting the clinical efficacy of LLLT + IPL therapy in MGD. Future research should evaluate its long-term safety and efficacy and compare it with alternative treatments., 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 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)
Published: 2024
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47. Validation Requirements for AI-based Intervention-Evaluation in Aging and Longevity Research and Practice.

Author: Fuellen G, Kulaga A, Lobentanzer S, Unfried M, Avelar RA, Palmer D, and Kennedy BK
Abstract: The field of aging and longevity research is overwhelmed by vast amounts of data, calling for the use of Artificial Intelligence (AI), including Large Language Models (LLMs), for the evaluation of geroprotective interventions. Such evaluations should be correct, useful, comprehensive, explainable, and they should consider causality, interdisciplinarity, adherence to standards, longitudinal data and known aging biology. In particular, comprehensive analyses should go beyond comparing data based on canonical biomedical databases, suggesting the use of AI to interpret changes in biomarkers and outcomes. Our requirements motivate the use of LLMs with Knowledge Graphs and dedicated workflows employing, e.g., Retrieval-Augmented Generation. While naive trust in the responses of AI tools can cause harm, adding our requirements to LLM queries can improve response quality, calling for benchmarking efforts and justifying the informed use of LLMs for advice on longevity interventions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian K. Kennedy reports a relationship with Ponce de Leon Health that includes: consulting or advisory and equity or stocks. If there are other authors, they 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. Published by Elsevier B.V.)
Published: 2024
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48. Engineering Semiconducting Polymeric Nanoagonists Potentiate cGAS-STING Pathway Activation and Elicit Long Term Memory Against Recurrence in Breast Cancer.

Author: Yuan H, Qiu C, Wang X, Wang P, Yi L, Peng X, Xu X, Huang W, Bai Y, Wei J, Ma J, Wong YK, Fu C, Xiao W, Chen C, Long Y, Li Z, and Wang J
Abstract: Triple-negative breast cancer has an immunologically "cold" microenvironment, which leads to resistance to current immunotherapy. The activation of stimulator of interferon genes (STING) pathway has been thought a promising strategy to enhance immunotherapy efficacy. In this study, we adopted a comprehensive strategy that integrates innate immune responses with tumor-targeting photothermal therapy (PTT) to simultaneously tackle multiple immune-suppressive mechanisms in breast cancer. This semiconducting polymeric nanoagonists (DPTT-Mn Lipo NPs) mediated PTT can effectively initiate tumor cell apoptosis and induce ICD, thereby reprogramming the immunosuppressive TME and activating STING. We confirmed the modulation of the TME through the PTT-mediated ICD effect and the transactivation of the cGAS-STING pathway in immune cells of the TME due to the released dsDNA via ICD, such as macrophages and DCs. Indeed, DPTT-Mn Lipo NPs-mediated PTT promoted M1 polarization of tumor-associated macrophages, augmented T-cell infiltration, facilitated dendritic cell (DC) maturation, and regulated type I interferon factor secretion, leading to efficient tumor suppression. Most importantly, the combination of DPTT-Mn Lipo NPs-based PTT with a checkpoint blockade therapy (anti-PD-1) can elicit long-term immune memory besides tumor eradication. Collectively, this nano-system can systemically activate antitumor immunity through STING activation and potentially establish long-term memory against tumor recurrence., (© 2024 Wiley‐VCH GmbH.)
Published: 2024
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49. NIR-II Imaging for Tracking the Spatiotemporal Immune Microenvironment in Atherosclerotic Plaques.

Author: Shen L, Chen M, Su Y, Bi Y, Shu G, Chen W, Lu C, Zhao Z, Lv L, Zou J, Chen X, and Ji J
Abstract: The inflammatory immune microenvironment is responsible for atherosclerotic plaque erosion and rupture. Near-infrared-II (NIR-II) fluorescence imaging has the potential to continuously monitor the spatiotemporal changes in the plaque immune microenvironment. Herein, we constructed three different NIR-II probes based on benzo[1,2- c ;4,5- c ']bis[1,2,5]thiadiazole-4,7-bis(9,9-dioctyl-9 H -fluoren-2-yl)thiophene (denoted as BBT-2FT): VHPK/BBT-2FT NPs, where VHPK is a specific peptide targeting vascular cell adhesion molecule-1; iNOS/BBT-2FT NPs for modulating the polarization of M1 macrophages by inducible NO synthase (iNOS) antibodies; and Arg-1/BBT-2FT for counterbalancing the inflammatory responses of M1 macrophages. These tracers enable precise tracking of atherosclerotic plaques and M1 and M2 macrophages through NIR-II imaging. VHPK/BBT-2FT NPs can accurately trace atherosclerotic plaques at various stages. Arg-1/BBT-2FT NPs precisely located M2 macrophages in the early plaque microenvironment with upregulation of peroxisome proliferator-activated receptor γ (PPAR-γ), signal transducer and activator of transcription (STAT) 6, and ATP-binding cassette transporter A1 (ABCA1), indicating that M2 macrophage polarization is crucial for early plaque lipid clearance. Meanwhile, iNOS/BBT-2FT NPs accurately tracked M1 macrophages in the advanced plaque microenvironment. The results showed that M1 macrophage polarization induces the formation of an inflammatory microenvironment through anaerobic glycolytic metabolism and pyroptosis in the advanced hypoxic plaque microenvironment, as indicated by the upregulation of hypoxia-inducible factor 1 alpha (HIF-1α), STAT1, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), pyruvate dehydrogenase kinase 1 (PDK1), and glucose transporter 1 (GLUT-1). Combining immunological approaches with NIR-II imaging has revealed that hypoxia-induced metabolic reprogramming of macrophages is a key factor in dynamic changes in the immune microenvironment of atherosclerotic plaques. Furthermore, our strategy shows the potential for real-time diagnosis and clinical prevention of unstable plaque rupture in atherosclerosis.
Published: 2024
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50. Synthetic lethal strategies for the development of cancer therapeutics.

Author: Ngoi NYL, Gallo D, Torrado C, Nardo M, Durocher D, and Yap TA
Abstract: Synthetic lethality is a genetic phenomenon whereby the simultaneous presence of two different genetic alterations impairs cellular viability. Importantly, targeting synthetic lethal interactions offers potential therapeutic strategies for cancers with alterations in pathways that might otherwise be considered undruggable. High-throughput screening methods based on modern CRISPR-Cas9 technologies have emerged and become crucial for identifying novel synthetic lethal interactions with the potential for translation into biologically rational cancer therapeutic strategies as well as associated predictive biomarkers of response capable of guiding patient selection. Spurred by the clinical success of PARP inhibitors in patients with BRCA-mutant cancers, novel agents targeting multiple synthetic lethal interactions within DNA damage response pathways are in clinical development, and rational strategies targeting synthetic lethal interactions spanning alterations in epigenetic, metabolic and proliferative pathways have also emerged and are in late preclinical and/or early clinical testing. In this Review, we provide a comprehensive overview of established and emerging technologies for synthetic lethal drug discovery and development and discuss promising therapeutic strategies targeting such interactions., Competing Interests: Competing interests: D.G. is an employee of and holds shares in Repare Therapeutics. D.D. holds shares in Repare Therapeutics and Induxion Therapeutics. T.A.Y. is an employee of the University of Texas MD Anderson Cancer Center as Vice President and Head of Clinical Development in the Therapeutics Discovery Division, which has a commercial interest in DDR and other inhibitors (for example IACS30380/ART0380 was licensed to Artios); has acted as a consultant of AbbVie, AstraZeneca, Acrivon, Adagene, Almac, Aduro, Amphista, Artios, Athena, Atrin, Avoro, Axiom, Baptist Health Systems, Bayer, Beigene, Boxer, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research UK, Clovis, Cybrexa, Diffusion, EMD Serono, F-Star, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Guidepoint, Idience, Ignyta, I-Mab, ImmuneSensor, Impact, Institut Gustave Roussy, Intellisphere, Jansen, Kyn, MEI pharma, Mereo, Merck, Natera, Nexys, Novocure, OHSU, OncoSec, Ono Pharma, Pegascy, PER, Pfizer, Piper-Sandler, Prolynx, Repare, resTORbio, Roche, Schrodinger, Theragnostics, Varian, Versant, Vibliome, Xinthera, Zai Labs and ZielBio; is stockholder in Seagen; and has received institutional research funding from Acrivon, Artios, AstraZeneca, Bayer, Beigene, BioNTech, Blueprint, BMS, Clovis, Constellation, Cyteir, Eli Lilly, EMD Serono, Forbius, F-Star, Artios, GlaxoSmithKline, Genentech, Haihe, Ideaya, ImmuneSensor, Ionis, Ipsen, Jounce, Karyopharm, KSQ, Kyowa, Merck, Mirati, Novartis, Pfizer, Ribon Therapeutics, Regeneron, Repare, Rubius, Sanofi, Scholar Rock, Seattle Genetics, Tesaro, Vivace and Zenith. N.Y.L.N., C.T. and M.N. declare no competing interests., (© 2024. Springer Nature Limited.)
Published: 2024
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